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Is older age a poor prognostic factor in stage I and II endometrioid endometrial adenocarcinoma?

Prior studies have shown that age ≥70 years is associated with more aggressive non-endometrioid histology and worse survival in endometrial cancer. The purpose of this study is to assess if age is an independent poor prognostic factor in endometrioid histologies. Under an IRB-approved protocol, we identified patients with surgical stage I to II endometrioid endometrial adenocarcinoma from 1995 to 2008 at two institutions. Patients were divided into two groups based on age at diagnosis: Group A (age 50-69 years) and Group B (age≥70 years). All patients underwent hysterectomy, bilateral salpingoophorectomy, +/-pelvic/aortic lymphadenectomy and adjuvant therapy. Prognostic factors were evaluated by univariate and multivariate analyses. We identified 338 patients with stage IA to IIB endometrioid endometrial adenocarcinoma. The median age in Group A was 59 years (range 50-69) and Group B was 75 years (range 70-92). Patients in Group B were more likely to have hypertension (51% vs. 68%, p=0.006) and coronary artery disease (9% vs. 18%, p=0.03). There were no differences in progression-free or disease-specific survival, however, Group B had a worse overall survival (OS) (50.1 vs. 62.6 months, p=0.03). On univariate analysis, age (p=0.04), grade (p=0.006), and coronary artery disease (p=0.01) were associated with worse OS. After adjusting for grade and coronary artery disease, age was no longer a significant variable for OS (p=0.17).

After adjusting for other poor prognostic factors, age ≥70 years alone may not be a significant variable affecting overall survival in patients with early stage endometrioid endometrial adenocarcinoma.

Does prevalence of tick-borne encephalitis virus in ixodid tick collected from the republic of Korea during 2011-2012?

In this study, we demonstrated that TBEV-infected ticks have been distributed in the ROK, combined with our previous results. These results suggest that TBEV may exist in the ROK, and H. longicornis, H. flava, and I. nipponensis may be potential vectors of TBEV. In addition, these results emphasize the need for further epidemiological research of TBEV. We examined for the presence of RNA of TBEV by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) using ixodid ticks captured in 25 localities of 10 provinces. Ticks were collected by the flagging and dragging method or using sentinel BG traps at forests, grass thickets, and grassland. A total of 13,053 ticks belonging to two genera and four species were collected and pooled (1292 pools), according to collection site, species of tick, and developmental stage. Among 1292 pools, the envelope (E) protein gene of TBEV was detected using RT-nested PCR in 10 pools (3 pools of the 1,331 adult ticks and 7 pools of the 11,169 nymph ticks) collected from Gangwon-do province, Jeonrabuk-do province, and Jeju Island. The minimum infection rates for TBEV of Haemaphysalis longicornis, Haemaphysalis flava, and Ixodes nipponensis were 0.06%, 0.17%, and 2.38%, respectively. Phylogenetic analysis based on the partial E protein gene was performed to identify relationships between the TBEV strains. This showed that 10 Korean strains clustered with the Western subtype.

In this study, we investigated the prevalence of tick-borne encephalitis virus (TBEV) in ixodid ticks from various regions of the Republic of Korea (ROK) during 2011-2012 to identify whether TBEV is circulating and to determine the endemic regions of TBEV.

Do surgical expectations change depending on first time surgery or reoperation?

To assess whether patients undergoing lumbar spine surgery for the first time (Group 1) had different expectations from those undergoing lumbar spine surgery for a failed previous procedure (Group 2). A prospective study that included 77 patients. A set of self-reported questionnaires was pre-operatively administered including VAS, Oswestry Disability Index (ODI), Zung Depression Scale and the NASS lumbar spine questionnaire (expectations scale). Fifty-six patients in Group 1 and 21 patients in Group 2. Both groups had high expectations with regard to the surgical procedure (n.s.). Depressed patients, despite being more disabled than non-depressed according to ODI (p 0.001), had similar expectations than non-depressed patients (n.s.).

Patients' expectations remained very high despite having had a failed previous surgery for the same procedure.

Are proprotein convertase subtilisin kexin type 9 null mice protected from postprandial triglyceridemia?

Proprotein convertase subtilisin kexin type 9 (PCSK9) is a natural inhibitor of the low-density lipoprotein receptor, and its deficiency in humans results in low plasma LDL-cholesterol and protection against cardiovascular disease. We explored whether PCSK9 expression impacts postprandial triglyceridemia, another important cardiovascular risk factor. Real-time PCR and confocal microscopy were used to show that PCSK9 is expressed throughout the entire small intestine and in human enterocytes. On olive oil gavage, PCSK9-deficient mice showed a dramatically decreased postprandial triglyceridemia compared with their wild-type littermates. Lymph analysis revealed that intestinal TG output is not quantitatively modified by PCSK9 deletion. However, PCSK9-/- mice present with a significant reduction of lymphatic apoB secretion compared to PCSK9+/+ mice. Modulating PCSK9 expression in polarized CaCo-2 cells confirmed the relationship between PCSK9 and apoB secretion; PCSK9-/- mice consistently secrete larger TG-rich lipoprotein than wild-type littermates. Finally, kinetic studies showed that PCSK9-deficient mice have an increased ability to clear chylomicrons compared to wild-type littermates.

These findings indicate that in addition to its effect on LDL-cholesterol, PCSK9 deficiency might protect against cardiovascular disease by reducing postprandial triglyceridemia.

Are home and eating environments associated with saturated fat intake in children in rural West Virginia?

To describe sociodemographic, environmental, and knowledge factors in relation to self-reported, energy-adjusted saturated fat consumption among children in rural West Virginia. Three hundred twenty-five 5th graders who participated in the Coronary Artery Risk Detection in Appalachian Communities Project conducted in 3 rural counties in West Virginia in 1998-1999. A cross-sectional survey based on self-reported information collected using a food frequency questionnaire, a nutrition knowledge questionnaire, and a family composition questionnaire. Descriptive statistics and multiple linear regression analysis. The mean percentage of energy from total fat was 31.8% +/- 4.9 and from saturated fat was 11.8% +/- 2.3. Energy-adjusted saturated fat intake was significantly higher among children with higher frequencies of breakfast and late-night snacks prepared away from home, and in households with single mothers. Variables associated with higher energy-adjusted saturated fat intake with marginal statistical significance (P=.05-.10) included attendance at schools with a higher percentage of students receiving free or reduced-price lunch, usual breakfast location other than home or school, and less knowledge about low-fat, low-sodium foods. Frequent late-night snacks prepared away from home and living with single mothers remained as significant correlates of energy-adjusted saturated fat intake independent of other hypothesized determinants.

Efforts to reduce saturated fat intake among children in rural areas should focus on food prepared away from home. Nutrition-related behaviors of single mothers should be explored further.

Does ballism after stroke respond to standard physical therapeutic interventions?

To report the effects of noninvasive standard physical therapy (PT) interventions on an involuntary movement disorder after stroke. Single case with clinical follow-up over 2 years. Inpatient stroke and rehabilitation services and outpatient clinic. A man with acute bilateral ballism after unilateral subthalamic infarction. Rhythmic coordinated bilateral limb movements and firm tactile stimulation to the hand. We had not anticipated that dyskinesia itself would specifically improve during treatment. Consequently, we used qualitative clinical observations, including review of videotaped performance, and self-reported limb control. Hypotheses concerning treatment effects were developed after data collection. Involuntary movements recurrently improved within treatment sessions.

PT may improve dyskinesia after stroke. The benefit may be adjunctive or alternative to current invasive treatments of movement disorders after brain injury and merits confirmation. The improvements are consistent with current research indicating that (1) intact cortical, subcortical, cerebellar, and spinal areas interact to generate bilateral rhythmic limb movements that can overcome dyskinesia and (2) tactile stimulation can improve motor deficits associated with basal ganglia disorders. Finally, because functional activities assessments improved our evaluation of ballism, these should be routinely used along with conventional neurologic examination to assess involuntary movement disorders.

Does student promotions committee appearance predict below-average performance during internship?

Medical educators grapple with predicting performance of graduates identified as struggling during medical school. Students appear before student promotions committees (SPCs) for multiple cognitive and noncognitive reasons and performance outcomes for this cohort have not been well defined in the literature. To determine the predictive validity of SPC appearance with respect to performance on a Program Director's (PD's) Evaluation Form completed at the end of internship (PGY-1). Residents were classified as "below average," "average," or "above average" based on PD Evaluation Form ratings. This PD instrument has been shown to be feasible, reliable, and valid. Below-average residents were defined as having a below-average rating on any question on the PD Evaluation Form. We compared SPC and non-SPC cohorts with respect to these PD Evaluation Form ratings. The t test was used for statistical analysis. Seven years of graduating classes from our institution were included. Of students who graduated from our institution, 119 of 856 students (14%) were presented at our SPC during medical school during our study period. There were 196 residents (23%) identified as below average. The PD Evaluation Form response rate for this period was 77%. Students who appeared at our SPC were significantly more likely to have below-average scores for almost all PD Evaluation Form questions with small to moderate effect sizes.

Students who appear before SPCs are at higher risk of below-average performance as rated by a PD Evaluation Form at the end of PGY-1. However, only a minority of trainees that appeared before our SPC received below-average ratings during internship. These data provide predictive validity evidence that SPC appearance during medical school does identify below average performance during internship. Our data support that SPC appearance during medical school, regardless of cause, is a risk for below average performance during internship.

Does oral administration of cytosolic PLA2 inhibitor arachidonyl trifluoromethyl ketone ameliorate cauda equina compression injury in rats?

Phospholipase A2 (PLA2)-derived proinflammatory lipid mediators such as prostaglandin E2 (PGE2), leukotrienes B4 (LTB4), lysophosphatidylcholine (LPC), and free fatty acids (FFA) are implicated in spinal cord injury (SCI) pathologies. Reducing the levels of these injurious bioactive lipid mediators is reported to ameliorate SCI. However, the specific role of the group IVA isoform of PLA2 cytosolic PLA2 (cPLA2) in lumbar spinal canal stenosis (LSS) due to cauda equina compression (CEC) injury is not clear. In this study, we investigated the role of cPLA2 in a rat model of CEC using a non-toxic cPLA2-preferential inhibitor, arachidonyl trifluoromethyl ketone (ATK). LSS was induced in adult female rats by CEC procedure using silicone blocks within the epidural spaces of L4 to L6 vertebrae. cPLA2 inhibitor ATK (7.5 mg/kg) was administered by oral gavage at 2 h following the CEC. cPLA2-derived injurious lipid mediators and the expression/activity of cPLA2, 5-lipoxygenase (5-LOX), and cyclooxygenase-2 (COX-2) were assessed. ATK-treated (CEC + ATK) were compared with vehicle-treated (CEC + VEH) animals in terms of myelin levels, pain threshold, and motor function. ATK treatment of CEC animals reduced the phosphorylation of cPLA2 (pcPLA2) determined by Western blot, improved locomotor function evaluated by rotarod task, and reduced pain threshold evaluated by mechanical hyperalgesia method. Levels of FFA and LPC, along with PGE2 and LTB4, were reduced in CEC + ATK compared with CEC + VEH group. However, ATK treatment reduced neither the activity/expression of 5-LOX nor the expression of COX-2 in CEC + VEH animals. Increased cPLA2 activity in the spinal cord from CEC + VEH animals correlated well with decreased spinal cord as well as cauda equina fiber myelin levels, which were restored after ATK treatment.

The data indicate that cPLA2 activity plays a significant role in tissue injury and pain after LSS. Reducing the levels of proinflammatory and tissue damaging eicosanoids and the deleterious lipid mediator LPC shows therapeutic potential. ATK inhibits cPLA2 activity, thereby decreasing the levels of injurious lipid mediators, reducing pain, improving functional deficits, and conferring protection against LSS injury. Thus, it shows potential for preclinical evaluation in LSS.

Does weight suppression predict total weight gain and rate of weight gain in outpatients with anorexia nervosa?

The present study sought to replicate the finding of Wildes and Marcus, Behav Res Ther, 50, 266-274, 2012 that higher levels of weight suppression at pretreatment predict greater total weight gain, faster rate of weight gain, and bulimic symptoms amongst patients admitted with anorexia nervosa. Participants were 56 women with anorexia nervosa diagnosed by using strict or lenient weight criteria, who were participating in a randomized controlled psychotherapy trial (McIntosh et al., Am J Psychiatry, 162, 741-747, 2005). Thirty-five women completed outpatient treatment and post-treatment assessment. Weight suppression was the discrepancy between highest lifetime weight at adult height and weight at pretreatment assessment. Outcome variables were total weight gain, rate of weight gain, and bulimic symptoms in the month prior to post-treatment assessment [assessed using the Eating Disorders Examination (Fairburn et al., Binge-Eating: Nature, Assessment and Treatment. New York: Guilford, 1993)]. Weight suppression was positively associated with total weight gain and rate of weight gain over treatment. Regression models showed that this association could not be explained by covariates (age at onset of anorexia nervosa and treatment modality). Weight suppression was not significantly associated with bulimic symptoms in the month prior to post-treatment assessment, regardless of whether bulimic symptoms were examined as continuous or dichotomous variables.

The present study reinforces the previous finding that weight suppression predicts total weight gain and rate of weight gain amongst patients being treated for anorexia nervosa. Methodological issues may explain the failure of the present study to find that weight suppression predicts bulimic symptoms. Weight suppression at pretreatment for anorexia nervosa should be assessed routinely and may inform treatment planning.

Is high folate intake associated with lower breast cancer incidence in postmenopausal women in the Malmö Diet and Cancer cohort?

Epidemiologic studies of associations between folate intake and breast cancer are inconclusive, but folate and other plant food nutrients appear protective in women at elevated risk. The objective was to examine the association between folate intake and the incidence of postmenopausal breast cancer. This prospective study included all women aged >or=50 y (n = 11699) from the Malmö Diet and Cancer cohort. The mean follow-up time was 9.5 y. We used a modified diet-history method to collect nutrient intake data. At the end of follow-up, 392 incident invasive breast cancer cases were verified. We used proportional hazard regression to calculate hazard ratios (HRs). Compared with the lowest quintile, the incidence of invasive breast cancer was reduced in the highest quintile of dietary folate intake (HR: 0.56; 95% CI: 0.35, 0.90; P for trend = 0.02); total folate intake, including supplements (HR: 0.56; 95% CI: 0.34, 0.91; P for trend = 0.006); and dietary folate equivalents (HR: 0.59; 95% CI: 0.36, 0.97; P for trend = 0.01).

A high folate intake was associated with a lower incidence of postmenopausal breast cancer in this cohort.

Does first outcome result after total knee and hip replacement from the Lithuanian arthroplasty register?

In 2010, the Lithuanian Association of Arhtroplasty was established and on January 1, 2011, initiated a national study of all reoperations after total knee (TKR) and total hip replacement (THR) in Lithuania. The aim of the study was to investigate the revision rates after TKR and THR at two years follow-up. Lithuanian patients undergoing primary TKR and THR from January 1, 2011, to December 31, 2012, were included in the study. The patient, surgery and prosthetic implantation data were collected via internet database. For reoperations we recorded the reason and type of revision, primary implantation date. We analyzed implant survival rates using any revision as an endpoint on included primary procedures, performed until September 1, 2013. The completeness of the register verified with state patients fund data reached 85% of all replacements. Out of 3823 primary TKR during the study period 25 revisions were performed with overall implant survival rate 99%. The main reason for knee revision was infections. During the inclusion period we registered 6072 primary THR and 149 revisions with overall implant survival rate 97%. Recurrent dislocation of prosthetic component was the main reason for hip revision. Significantly inferior survival results for femoral neck fracture patients were observed as compared with patients operated for osteoarthritis. Posterior approach as compared to others significantly affected inferior implant survival rates for femoral neck fracture patients.

The overall survival after total knee and hip replacements revealed a high treatment quality of this surgery in Lithuania.

Is low hemoglobin associated with poor functional outcome after non-traumatic , supratentorial intracerebral hemorrhage?

The impact of anemia on functional outcome and mortality in patients suffering from non-traumatic intracerebral hemorrhage (ICH) has not been investigated. Here, we assessed the relationship between hemoglobin (HB) levels and clinical outcome after ICH. One hundred and ninety six patients suffering from supratentorial, non-traumatic ICH were extracted from our local stroke database (June 2004 to June 2006). Clinical and radiologic computed tomography data, HB levels on admission, mean HB values and nadir during hospital stay were recorded. Outcome was assessed at discharge and 3 months using the modified Rankin score (mRS). Forty six (23.5%) patients achieved a favorable functional outcome (mRS <or= 3) and 150 (76.5%) had poor outcome (mRS 4 - 6) at discharge. Patients with poor functional outcome had a lower mean HB (12.3 versus 13.7 g/dl, P < 0.001) and nadir HB (11.5 versus 13.0 g/dl, P < 0.001). Ten patients (5.1%) received red blood cell (RBC) transfusions. In a multivariate logistic regression model, the mean HB was an independent predictor for poor functional outcome at three months (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.92, P = 0.007), along with National Institute of Health Stroke Scale (NIHSS) at admission (OR 1.17, 95% CI 1.11 - 1.24, P < 0.001), and age (OR 1.08, 95% CI 1.04 - 1.12, P < 0.001).

We report an association between low HB and poor outcome in patients with non-traumatic, supratentorial ICH. While a causal relationship could not be proven, previous experimental studies and studies in brain injured patients provide evidence for detrimental effects of anemia on brain metabolism. However, the potential risk of anemia must be balanced against the risk of harm from red blood cell infusion.

Do laser flare photometry in the therapeutic management of bacterial chronic pseudophakic endophthalmitis?

To evaluate laser flare photometry in measuring aqueous humor inflammation in chronic pseudophakic endophthalmitis. Department of Ophthalmology, Pitié Salpétrière Hospital, Paris, France. This retrospective review comprised eyes with chronic pseudophakic endophthalmitis that were evaluated by slitlamp and laser flare photometry at admission and during follow-up. Nine eyes of 8 patients were reviewed. The laser flare photometry values were significantly reduced by antibiotic treatment in all eyes. The laser flare photometry values increased after antibiotic treatment was withdrawn in 7 eyes. Early detection of the relapse by laser flare photometry was confirmed at the slitlamp examination in the following days.

Laser flare photometry, a noninvasive objective tool, was useful in monitoring the evolution of chronic pseudophakic endophthalmitis. Early detection of an increase in flare could lead to a close follow-up. The prompt modification of therapeutic intervention could help preserve a favorable visual outcome.

Does the New York University nerve sparing algorithm decrease the rate of positive surgical margins following radical retropubic prostatectomy?

We developed an algorithm that prospectively defines when to excise the neurovascular bundles during radical retropubic prostatectomy with the goal of maximizing the performance of nerve sparing procedures while minimizing positive surgical margins. From January 1 to December 31, 2000 a single surgeon performed 272 radical retropubic prostatectomies and 263 were performed from January 1 to December 31, 2001. A single pathologist analyzed all specimens with positive margins. There were no prospectively defined criteria to guide decisions regarding excision of the neurovascular bundles in the 2000 study cohort. Gleason score, percent tumor volume and perineural invasion were independently analyzed in the biopsy specimens according to the site of origin (right versus left side) for the 2001 group only. The ipsilateral neurovascular bundle was excised for Gleason 6 or less tumors when there were 50% or greater tumor volume in the biopsy specimen and perineural invasion, for Gleason 7 tumors when there was 30% or greater tumor volume, or perineural invasion and for Gleason 8 to 10 tumors when there was 10% or greater tumor volume, or perineural invasion. There were no statistically significant differences between the 2000 and 2001 groups in regard to preoperative prostate specific antigen, clinical and pathological stage, biopsy Gleason score and percent tumor volume in the surgical specimen. There was a statistically significant decrease in the incidence of positive margins between the 2000 and 2001 groups (14% versus 8%, p = 0.027). The lower positive margin rate was not achieved because of a tendency to excise more neurovascular bundles since a significantly greater percent of neurovascular bundles was preserved in the 2001 group. The sensitivity, specificity, positive and negative predictive values, and accuracy of our algorithm were 18%, 93%, 28%, 89% and 84%, respectively. In sides of the prostate with extraprostatic extension ipsilateral wide excision of the neurovascular bundle was associated with positive margins in 33% of cases compared with 22% when the neurovascular bundle was preserved (p = 0.42).

The New York University nerve sparing algorithm prospectively defines when to excise the neurovascular bundle based on Gleason score, perineural invasion and tumor volume in the biopsy specimen. Use of this algorithm decreases positive surgical margin rates, while significantly increasing the preservation of neurovascular bundles.

Does fasudil regulate T cell responses through polarization of BV-2 cells in mice experimental autoimmune encephalomyelitis?

Fasudil, a selective Rho kinase (ROCK) inhibitor, has been shown to alleviate the severity of experimental autoimmune encephalomyelitis (EAE) via attenuating demyelination and neuroinflammation. The aim of this study was to investigate the effects of fasudil on interactions between macrophages/microglia and T cells in a mice EAE model. Mouse BV-2 microglia were treated with IFN-γ and fasudil. Cell viability was detected with MTT assay. BV-2 microglia polarization was analyzed using flow cytometry. Cytokines and other proteins were detected with ELISA and Western blotting, respectively. Mice were immunized with MOG35-55 to induce EAE, and then treated with fasudil (40 mg/kg, ip) every other day from d 3 to d 27 pi. Encephalomyelitic T cells were prepared from the spleen of mice immunized with MOG35-55 on d 9 pi. Treatment of mouse BV-2 microglia with fasudil (15 μg/mL) induced significant phenotype polarization and functional plasticity, shifting M1 to M2 polarization. When co-cultured with the encephalomyelitic T cells, fasudil-treated BV-2 microglia significantly inhibited the proliferation of antigen-reactive T cells, and down-regulated IL-17-expressing CD4(+) T cells and IL-17 production. Furthermore, fasudil-treated BV-2 microglia significantly up-regulated CD4(+)CD25(high) and CD4(+)IL-10(+) regulatory T cells (Tregs) and IL-10 production, suggesting that the encephalomyelitic T cells had converted to Tregs. In EAE mice, fasudil administration significantly decreased both CD11b(+)iNOS(+) and CD11b(+)TNF-α(+) M1 microglia, and increased CD11b(+)IL-10(+) M2 microglia.

Fasudil polarizes BV-2 microglia into M2 cells, which convert the encephalomyelitic T cells into Tregs in the mice EAE model.

Are common variants related to serum uric acid concentrations associated with glucose metabolism and insulin secretion in a Chinese population?

Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion. We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined. SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively).

Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.

Does pancreatic intubation facilitated by methylene blue injection decrease the risk for postpapillectomy acute pancreatitis?

Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis. Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy. ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%).

Endoscopic papillectomy is safe and effective in the hands of experts. Pancreatic-duct stent placement in fewer cannulation attempts could be facilitated by injection of MB before papillectomy, and this decreases the risk for postprocedure pancreatitis. Recurrences can be managed endoscopically, but with a higher risk for pancreatitis.

Macular degeneration: do conventional measurements of impaired visual function equate with visual disability?

To examine the relation between measures of vision and ability to perform daily living tasks in those visually impaired with macular degeneration. A visual functioning index (daily living tasks dependent on vision: DLTV) was used to evaluate patients' perception of their ability to perform vision dependent tasks. Distance visual acuity, near visual acuity, reading speed, and contrast sensitivity were measured in all patients. In addition, a new measure of reading ability was derived, designated the reading index. This takes into account both the size of the text read and the time to read it and is equivalent to the reading speed in words per minute divided by text size in M. The reading index was found to show best associations with the majority of items within the DLTV. Stepwise regression identified the combination of reading index and distance visual acuity as having the best associations with DLTV items. The present study also demonstrated that specific levels of vision as measured by acuity, reading index, and contrast sensitivity corresponded with different perceived amounts of difficulty in the performance of daily living tasks.

This study showed that reading index is valuable in predicting the ability to perform daily living tasks and therefore may be useful in the visual assessment of the visually impaired individual. In addition, this study identified specific levels of vision at which individuals reported different degrees of difficulty in performing daily living tasks.

Does [ Apoptosis inducing factor mediate cisplatin-induced apoptosis of renal tubular epithelial cells ]?

To investigate the involvement of apoptosis inducing factor (AIF) in caspase-independent pathway mediating apoptosis of cultured renal tubular epithelial cells induced by cisplatin (CP). Western Blot analysis and real-time PCR were performed to detect cytosol AIF (cAIF), nuclear AIF (nAIF) and AIF mRNA expression in cultured renal epithelial cells (HK-2) treated with cisplatin (CP) at various concentrations (0 - 200 micromol/L) and time courses (0 - 12 h). Immunofluorescence analysis was used to detect the AIF protein distribution in HK-2 cells. Pan-caspase inhibitor (Z-VAD-FMK) and AIF-siRNA treatment, TUNEL and flow cytometer were used to measure the suppression of apoptosis induced by CP in HK-2 cells. The expressions of cAIF, nAIF protein and AIF mRNA were all increased to some extent in HK-2 cells treated with CP at various concentrations and time points. cAIF expression was 2.3-fold (P < 0.05) increased after 25 micromol/L CP treatment for 12 h and 1.7-fold (P < 0.01) increased after 50 micromol/L CP treatment for 3 h, compared with that of control groups, and showed a concentration- and time-dependent increment. The nAIF expression reached a peak (4.3-fold increase) (P < 0.005) after 150 micromol/L CP treatment for 12 h and 3.7-fold incease (P < 0.05) after 50 micromol/L CP treatment for 9 h, compared with that of the 25 micromol/L group and 3 h group, respectively. The expression of nAIF was approximately consistent with cleaved-PARP expressive pattern. Real-time PCR showed that AIF mRNA increased gradually with prolonged treatment with 50 micromol/L CP and reached a peak at 9 h. Immunofluorescence assay showed AIF translocation from cytosol to nuclei in some cultured HK-2 cells treated with CP. Applying pan-caspase inhibitor (Z-VAD-FMK) and AIF-siRNA to CP-treated HK-2 cells, the apoptotic rates were decreased by 60.1% and 39.2%, respectively. The inhibitory effect on HK-2 cell apoptosis was even more significant with combination of both Z-VAD-FMK and AIF-siRNA.

The AIF activation and translocation to nuclei with the increment of its mRNA expression mediates CP-induced apoptosis of renal tubular epithelial cells in vitro. It may provide a new therapeutic target for protecting from nephrotoxciity of cisplatin.

Does caveolin-1 attenuate hydrogen peroxide-induced oxidative damage to lung carcinoma cells?

Oxidative stress has been shown to play an important role in cancer progression. In lung cancer, increasing expression of caveolin-1 (Cav-1) has been found in both primary and metastatic carcinomas and may be critical in the regulation of the oxidative status of cancer cells. Using molecular and pharmacological manipulations, the role of Cav-1 in regulating cellular oxidative status in lung cancer cells was investigated. The level of Cav-1 was determined by western blot analysis and reactive oxygen species (ROS) were detected by specific fluorescence probes. The treatment of lung cancer H460 cells with hydrogen peroxide (H(2)O(2)) significantly up-regulated ROS inside the cells and contributed to cell apoptosis. While cells stably transfected with Cav-1 overexpressing plasmids (H460/Cav-1) exhibited decreased ROS signal and attenuated cell death rate, shRNACav-1 transfected (H460/shCav-1) cells showed enhanced ROS signal and increased cell damage. The use of specific superoxide anion and the hydrogen peroxide detecting assays and hydroxyl radical inhibition assay indicated that the variable oxidative stress found in these cells was mainly due to the alteration of the cellular hydroxyl radical level.

A novel role of Cav-1 protein is the suppression of cellular oxidative stress induced by H(2)O(2).

Should age be a contraindication for degenerative lumbar surgery?

The purpose of this study was to evaluate and compare disability, quality of life and satisfaction outcomes between young people and elderly who were operated on for degenerative lumbar disease. A database of 263 patients undergoing lumbar surgery for degenerative conditions was collected. There were 74 patients who were 65 years old or above and 189 who were below 65 who had complete preoperative and 2-year postoperative HRQOL data measures: ODI, SF-36 and COMI. There were no significant differences in the outcomes between the two age groups (p > 0.05). An improvement from baseline in all quality of life measures in the two age groups was observed. A median improvement of 6.0 points was found in the ODI in the younger patients versus 12.0 in older ones. A median improvement in the SF36 physical component score of 6.95 was seen in the younger group while improvement was reported at 6.36 points in patients over 65. The SF36 mental component score improved by 4.48 points and 4.96 points, respectively. COMI improved a median of 1.2 points in both groups. In terms of satisfaction, 66.9 % of the younger patients were pleased or very pleased whereas this was found to be 59.7 % for the older group.

Older patients can see substantial clinical improvement after degenerative lumbar disease surgery similar to that obtained in younger patients in terms of quality of life and satisfaction. The improvement in terms of the disability is greater for older patients. Thus, age should not be a contraindication for this procedure.

Does simvastatin inhibit cigarette smoking-induced emphysema and pulmonary hypertension in rat lungs?

In cigarette smoking-induced chronic obstructive pulmonary disease, structural and functional derangements are characterized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase inhibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including antiinflammation, scavenging reactive oxygen species, restoring endothelial function, and antithrombogenesis, all of which can counteract the harmful effects of cigarette smoking. We performed assays to determine whether simvastatin could attenuate lung damage induced by chronic cigarette smoking in rats. In Sprague-Dawley rats exposed to cigarette smoke for 16 weeks, morphologic changes in the lungs and pulmonary arterial pressure were examined. Simvastatin inhibited lung parenchymal destruction and development of pulmonary hypertension, and also inhibited peribronchial and perivascular infiltration of inflammatory cells and induction of matrix metalloproteinase-9 activity in lung tissue. Simvastatin additionally prevented pulmonary vascular remodeling and the changes in endothelial nitric oxide synthase expression induced by smoking. In human lung microvascular endothelial cells, simvastatin increased expression of endothelial nitric oxide synthase mRNA.

Simvastatin ameliorated the structural and functional derangements of the lungs caused by cigarette smoking, partly by suppressing inflammation and matrix metalloproteinase-9 induction and preventing pulmonary vascular abnormality. These findings indicate that statins may play a role in the treatment of cigarette smoking-induced chronic obstructive pulmonary disease.

Does resident interpretation of emergency CT scan in the evaluation of acute appendicitis?

Radiology resident interpretation of computed tomographic (CT) scans at academic institutions often guides management of cases of suspected acute appendicitis in the emergency department. The purpose of this study was to compare resident and faculty interpretation of CT scans obtained for acute appendicitis. From December 16, 1999, to July 13, 2000, CT was performed in 103 consecutive patients between the hours of 9:00 PM and 8:00 AM who were suspected of having acute appendicitis. The authors compared the residents' preliminary written interpretations with both the final reports written by the faculty and the surgical findings. The faculty interpreting the CT scans were aware of resident interpretations but were not aware that a study was being conducted. The final faculty interpretation and the preliminary resident interpretation were identical in 96 of the 103 patients (93%; 95% confidence interval: 87.8%, 97.2%). In only one patient was a scan originally interpreted as negative interpreted as positive by the faculty member. Clinically, the patient did not have acute appendicitis, and surgery was not perforrmed.

In the diagnosis of acute appendicitis, image interpretations made by adequately trained radiology residents can be expected to closely match those of the radiology faculty, and the practice of after-hours interpretation of such studies by radiology residents is safe.

Do early postoperative alterations of ventilation parameters after tracheostomy in major burn injuries?

In patients with major burn injuries mechanical ventilation is often required for longer periods. Tracheostomy (TS) plays an integral role in airway management. We investigated the effect of TS on ventilation parameters within 8 hours after TS. A retrospective analysis of severely burned patients admitted to the burn unit of a German University Hospital was performed. Ventilation parameters 8 hours before and after TS were registered. A retrospective analysis of 20 patients which received surgical TS was performed. Mean age was 52+/-19 years. Mean abbreviated burned severity index (ABSI) was 8.3+/-2.2. A mechanical ventilation was required for 14.3+/-4.8 days. TS was performed on day 7+/-4. Inspiratory oxygen concentration (FiO(2)) (p<0.001), peak inspiratory pressure (p<0.001), positive end-expiratory pressure (p=0.003) and pulmonary resistance (p<0.001) were reduced significantly after TS. The arterial partial pressure of oxygen/FiO(2)-ratio increased significantly after TS (p<0.001).

We demonstrate that TS reduces invasiveness of ventilation in severely burned patients and by this can optimize lung protective ventilation strategy.

Is traditional food consumption associated with higher nutrient intakes in Inuit children attending childcare centres in Nunavik?

To describe traditional food (TF) consumption and to evaluate its impact on nutrient intakes of preschool Inuit children from Nunavik. A cross-sectional study. Dietary intakes of children were assessed with a single 24-hour recall (n=217). TF consumption at home and at the childcare centres was compared. Differences in children's nutrient intakes when consuming or not consuming at least 1 TF item were examined using ANCOVA. A total of 245 children attending childcare centres in 10 communities of Nunavik were recruited between 2006 and 2010. The children's mean age was 25.0±9.6 months (11-54 months). Thirty-six percent of children had consumed at least 1 TF item on the day of the recall. TF contributed to 2.6% of total energy intake. Caribou and Arctic char were the most reported TF species. Land animals and fish/shellfish were the main contributors to energy intake from TF (38 and 33%, respectively). In spite of a low TF intake, children who consumed TF had significantly (p<0.05) higher intakes of protein, omega-3 fatty acids, iron, phosphorus, zinc, copper, selenium, niacin, pantothenic acid, riboflavin, and vitamin B12, and lower intakes of energy and carbohydrate compared with non-consumers. There was no significant difference in any of the socio-economic variables between children who consumed TF and those who did not.

Although TF was not eaten much, it contributed significantly to the nutrient intakes of children. Consumption of TF should be encouraged as it provides many nutritional, economic, and sociocultural benefits.

Do an update expert opinion on management and research strategies in Parkinson 's disease psychosis?

Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed. This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed.

Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.

Does subconjunctival injection of low-molecular-weight heparin-taurocholate 7 inhibit corneal neovascularization?

To evaluate the effects of a subconjunctival injection of low-molecular-weight heparin-taurocholate 7 (LHT7) on corneal neovascularization (CoNV) in rats. Twenty-four Sprague-Dawley rats were divided into 4 groups of 6 animals each. Corneal centers were cauterized by the application of a silver/potassium nitrate solution for 8 seconds. Either 0.02 or 0.04 mL of 25 mg/mL of LHT7 (low- and high-LHT7 groups, respectively) was subconjunctivally injected on days 2 and 4 after the cauterization was done; 0.02 mL of 25 mg/mL of bevacizumab was injected into rats in the positive control group, with normal saline (NS) being administered to a negative control group. Digital photographs of the cornea were taken 1 and 2 weeks later to calculate the percentage of CoNV using the area of the neovascularized cornea. To compare the differences in CoNV between weeks 1 and 2, the change in CoNV was calculated by subtracting the percentage of CoNV at 1 week from that at 2 weeks. The percentage of CoNV did not differ among the 4 groups either 1 or 2 weeks after the cauterization (P > 0.05). In all groups except the NS group, the percentage of CoNV significantly decreased at 2 weeks compared with that at 1 week (all P < 0.05). Moreover, the changes of CoNV in the high-LHT7 and bevacizumab groups significantly decreased compared with that in the NS group (all P < 0.05). Two corneal stromal hemorrhages occurred, 1 in each LHT7 group.

Despite complications, including corneal stromal hemorrhage, subconjunctival injection of LHT7 attenuated CoNV after chemical cauterization.

Do red cell transfusions increase the risk of necrotizing enterocolitis in premature infants?

To test the hypothesis that red blood cell (RBC) transfusions increase the risk of necrotizing enterocolitis (NEC) in premature infants, we investigated whether the risk of "transfusion-associated" NEC is higher in infants with lower hematocrits and advanced postnatal age. Retrospective comparison of NEC patients and control patients born at<34 weeks gestation. The frequency of RBC transfusions was similar in NEC patients (47/93, 51%) and control patients (52/91, 58%). Late-onset NEC (>4 weeks of age) was more frequently associated with a history of transfusion(s) than early-onset NEC (adjusted OR, 6.7; 95% CI, 1.5 to 31.2; P = .02). Compared with nontransfused patients, RBC-transfused patients were born at earlier gestational ages, had greater intensive care needs (including at the time of onset of NEC), and longer hospital stay. A history of RBC transfusions within 48-hours before NEC onset was noted in 38% of patients, most of whom were extremely low birth weight infants.

In most patients, RBC transfusions were temporally unrelated to NEC and may be merely a marker of overall severity of illness. However, the relationship between RBC transfusions and NEC requires further evaluation in extremely low birth weight infants using a prospective cohort design.

Provision of continence pads by the continence services in Great Britain: fair all round?

The UK Department of Health guidelines for continence services recommended that maintenance products should be available to anyone in quantities appropriate to the individuals' needs and to children above the age of 4 years. Despite this, there is much anecdotal evidence of rationing products. The aim of this study was to examine to what extent services limited pad supplies and what criteria were in operation to govern the supply. A questionnaire exploring the current practice in conferring eligibility and prescribing and providing continence products was developed and distributed to all continence services in Great Britain, using a database of services. Data were analyzed from all returned questionnaires to all continence services on the Continence Foundation database and were also extracted from the 2006 National Audit of Continence Care for Older People. Few continence services employed clear and detailed criteria for issuing continence pads and, when present, written criteria used arbitrary cutoffs for measuring incontinence severity. Rationing was widespread, and the most common adult pad allowance was 4 per day. In addition, 59% of continence services provided pads to children below the recommended age of 4 years.

Distribution of continence pads was based upon arbitrary criteria. We recommend the development of a single assessment tool with clear criteria for provision of continence products throughout the United Kingdom. We also recommend that criteria limiting the number of continence pads supplied on a daily basis are transparent and explicit.

Does reference range for cardiac dimensions and blood flow velocity in preterm infants?

To establish reference ranges for cardiac dimensions and Doppler measurements in preterm infants. 79 infants of less than 34 weeks' gestation were examined by echocardiography on days 0, 7, and 28 after birth, to produce a set of reference ranges and to examine changes in these indices over the first month of life. The following dimensions were measured: interventricular septum, left ventricular posterior wall, left interventricular diameter at end systole and diastole, left atrium, and aortic root; Doppler measurements were made of maximum blood flow velocity (Vmax) through the pulmonary, aortic, mitral, and tricuspid valves. Reference ranges are given. Cardiac dimensions correlated well with gestation and birth weight but Vmax did not. There was a significant increase in measurements over time. The "normal" preterm infant also appeared to often have asymmetrical septal hypertrophy. Antenatal dexamethasone administration did not appear to affect the measurements.

There is a close correlation with both gestation and birth weight for all physical measurements. Echocardiograms in preterm babies clearly differ from those in older children and adults.

Do child Physical Activity Associations With Cardiovascular Risk Factors Differ by Race?

The objective of this study was to characterize the relationship between objectively-measured physical activity (PA) and cardiovascular risk factors in 7-year-old children and test the hypothesis that it differs by race. Cross-sectional study of 308 7-year-old children drawn from a major US metropolitan community. PA (moderate-to-vigorous, MVPA; light, LPA; and inactivity, IA) was measured by accelerometry (RT3). Cardiovascular risk factors included BMI, blood pressure, and serum lipids, glucose and insulin concentrations. General linear modeling was used to evaluate the independent associations between PA measures and cardiovascular risk factors and interactions by race. In black children, greater time spent in PA was independently associated with lower levels of triglycerides (MVPA and LPA, both p < .01), glucose (MVPA, p < .05), and insulin (MVPA, p < .01); these associations were not evident in white children. Across races, greater inactivity was independently associated with greater low-density lipoprotein cholesterol in overweight participants (p < .01) but not in normal weight participants. No PA measure was associated with BMI, systolic blood pressure, or high-density lipoprotein cholesterol.

In this cohort of 7-year-old children, the relationship between PA and some cardiovascular risk factors differed by race. These findings may have implications for targeting of PA promotion efforts in children.

Is early childhood social disadvantage associated with poor health behaviours in adulthood?

Individual health behaviours are considered important risk factors for cardiometabolic diseases. These behaviours may be socially patterned by early exposure to social disadvantage, but few studies have prospectively tested this hypothesis empirically. This study investigated whether childhood social disadvantage was associated with likelihood of engaging in less healthy behaviours 40 years later. Prospective data were analysed from the New England Family Study, a 2005-2007 adult follow-up of a cohort initiated in 1959-1966 (n = 565). Childhood social environment (age 7 years) was assessed using a cumulative index of socioeconomic and family stability factors. Logistic regression models evaluated associations between social disadvantage and each health-related behaviour and obesity in adulthood. Relative to low disadvantage, higher disadvantage was associated with 3.6-fold greater odds of smoking (95% CI = 1.9-7.0), 4.8-fold greater odds (in women only) of excess alcohol consumption (95% CI = 1.6-14.2) and 2.7-fold greater odds of obesity (95% CI = 1.3-5.5), but was not associated with unhealthy diet or physical inactivity.

These findings suggest childhood social disadvantage may contribute to adult cardiometabolic disease by predisposing children to adopt certain unhealthy behaviours. If replicated, such findings may support intervention strategies that target social environmental factors and behavioural pathways that are established early in life.

Does mistletoes and mutant albino shoot on woody plants as mineral nutrient traps?

Potassium, sulphur and zinc contents of mistletoe leaves are generally higher than in their hosts. This is attributed to the fact that chemical elements which are cycled between xylem and phloem in the process of phloem loading of sugars are trapped in the mistletoe, because these parasites do not feed their hosts. Here it is hypothesized that mutant albino shoots on otherwise green plants should behave similarly, because they lack photosynthesis and thus cannot recycle elements involved in sugar loading. The mineral nutrition of the mistletoe Scurrula elata was compared with that of albino shoots on Citrus sinensis and Nerium oleander. The potential for selective nutrient uptake by the mistletoe was studied by comparing element contents of host leaves on infected and uninfected branches and by manipulation of the haustorium-shoot ratio in mistletoes. Phloem anatomy of albino leaves was compared with that of green leaves. Both mistletoes and albino leaves had higher contents of potassium, sulphur and zinc than hosts or green leaves, respectively. Hypothetical discrimination of nutrient elements during the uptake by the haustorium is not supported by our data. Anatomical studies of albino leaves showed characteristics of release phloem.

Both albino shoots and mistletoes are traps for elements normally recycled between xylem and phloem, because retranslocation of phloem mobile elements into the mother plant or the host is low or absent. It can be assumed that the lack of photosynthetic activity in albino shoots and thus of sugars needed in phloem loading is responsible for the accumulation of elements. The absence of phloem loading is reflected in phloem anatomy of these abnormal shoots. In mistletoes the evolution of a parasitic lifestyle has obviously eliminated substantial feeding of the host with photosynthates produced by the mistletoe.

Does vitamin D 20,000 IU per Week for Five Years Prevent Progression From Prediabetes to Diabetes?

Vitamin D deficiency is associated with insulin resistance and risk of future diabetes. The objective of the study was to test whether supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes mellitus (T2DM). This was a randomized controlled trial performed in 2008 through 2015. The study was conducted at the clinical research unit at a teaching hospital. Five hundred eleven subjects (mean age 62 y, 314 males) with prediabetes diagnosed with an oral glucose tolerance test as part of the Tromsø Study 2007–2008 were included. A total of 256 were randomized to vitamin D and 255 to placebo. Twenty-nine subjects in the vitamin D and 24 in the placebo group withdrew because of adverse events. Interventions included vitamin D (cholecalciferol) 20 000 IU/wk vs placebo for 5 years. Annual oral glucose tolerance tests were performed. Progression to T2DM was the main outcome measure. Secondary outcomes were change in glucose levels, insulin resistance, serum lipids, and blood pressure. The mean baseline serum 25-hydroxyvitamin D level was 60 nmol/L (24 ng/mL). One hundred three in the vitamin D and 112 in the placebo group developed T2DM (hazard risk 0.90; 95% confidence interval 0.69–1.18, Cox regression, P = .45, intention to treat analysis). No consistent significant effects on the other outcomes were seen. Subgroup analyses in subjects with low baseline 25-hydroxyvitamin D yielded similar results. No serious side effects related to the intervention were recorded.

In subjects without vitamin D deficiency, vitamin D supplementation is unlikely to prevent progression from prediabetes to diabetes. Very large studies with inclusion of vitamin D-deficient subjects will probably be needed to show such a putative effect. This study tested if supplementation with vitamin D to subjects with prediabetes will prevent progression to type 2 diabetes (T2DM).

Does follicle curetting at the time of oocyte retrieval increase the oocyte yield?

To determine whether follicle curetting at the time of oocyte retrieval increases oocyte yield. Retrospective review of all patients who underwent oocyte retrieval from July 1, 2003 to June 30, 2005. Number of oocytes retrieved. retrieval time, number of cryopreserved embryos, pregnancy rates, and incidence of ovarian hyperstimulation syndrome. There were no differences in patient demographics, antral follicle count, cycle stimulation characteristics, fertilization rates, embryo quantity or quality, embryo cryopreservation rates, clinical pregnancy rates, live birth rates, or ovarian hyperstimulation syndrome between the groups. Retrievals that utilized curetting took three minutes longer. Follicle curetting significantly increased the number of oocytes retrieved, 13.9 +/- 0.6 compared to 11.4 +/- 0.6 oocytes without curetting (P = 0.003). The quantity of mature oocytes was also increased with curetting (10.3 +/- 0.5 versus 8.4 +/- 0.5, P = 0.006).

This study demonstrated that follicle curetting significantly increased oocyte yield. While it did not increase live birth rates, this increase in oocyte yield should lead to increased numbers of embryos for selection at transfer and increased embryos for cryopreservation.

Is hER3 a determinant for poor prognosis in melanoma?

The epidermal growth factor receptor family member HER3 is overexpressed in diverse human cancers and has been associated with poor prognosis in breast, lung, and ovarian cancer. However, the relevance of HER3 with regard to its prognostic significance and function in primary melanoma and metastases remains largely elusive. HER3 protein expression was analyzed immunohistochemically using tissue microarrays of 130 primary melanoma and 87 metastases relative to established clinical variables. The possibility of an influence of HER3 on melanoma cell proliferation, migration, invasion, and chemotherapy-induced apoptosis was studied in human melanoma cell lines. We show that HER3 is frequently expressed in malignant melanoma and metastases at elevated levels. High HER3 expression may serve as a prognostic marker because it correlates with cell proliferation, tumor progression, and reduced patient survival. Suppression of HER3 expression by RNA interference reduces melanoma cell proliferation, migration, and invasion in vitro. In addition, down-regulation of HER3 synergistically enhances dacarbazine-induced apoptosis. Moreover, monoclonal antibodies specific for the extracellular portion of HER3 efficiently block heregulin-induced proliferation, migration, and invasion of melanoma cell lines.

Our results provide novel insights into the role of HER3 in melanoma and point out new possibilities for therapeutic intervention.

Does mometasone furoate improve congestion in patients with moderate-to-severe seasonal allergic rhinitis?

A recent survey estimated that 85% of patients with allergic rhinitis experience nasal congestion. This symptom considerably impacts quality of life. To evaluate the effectiveness of mometasone furoate nasal spray (MFNS) in subjects with seasonal allergic rhinitis (SAR) experiencing moderate-to-severe nasal congestion. Data were obtained from 4 randomized, double-blind, placebo-controlled studies of MFNS 200 microg once daily in patients with SAR. Subject-evaluated nasal congestion score data (score range 0-3) from subjects receiving MFNS or placebo were analyzed as a pool and grouped according to baseline score (all pts. with scores >2.5, >2.75, or 3.0). The 2-week average change in score from baseline was analyzed. Significant improvements in mean nasal congestion score were seen with MFNS (n = 490) versus placebo (n = 492; p < 0.001). Overall, there was a 27% improvement in this score in patients receiving MFNS versus 13% with placebo. MFNS produced significant reductions in the nasal congestion score compared with placebo, even in patients with the most severe baseline congestion (0.98 vs 0.52; p < 0.001). Improvements in scores from baseline of 32%, 33%, and 34% were seen with MFNS versus 22%, 21%, and 18% with placebo (for baseline scores of >2.5, >2.75, or 3.0, respectively), confirming the effectiveness of MFNS regardless of congestion severity. This represents an improvement approximating a decrease from severe to moderate congestion or from moderate-to-severe to mild-to-moderate congestion. MFNS was well tolerated.

MFNS 200 microg once daily produces statistically significant improvements in nasal congestion score compared with placebo, alleviating severe congestion in patients with moderate-to-severe SAR.

Does monomethyl Auristatin E Phosphate inhibit Human Prostate Cancer Growth?

Bone metastasis from primary prostate cancer leads to markedly diminished quality of life with poor long-term survival. Bone seeking treatment options are limited with adverse consequences on rapidly proliferating tissues such as bone marrow. In the present study, we seek to determine the bone-enriching capabilities of monomethyl auristatin E phosphate (MMAEp), a derivative of the potent antimitotic monomethyl auristatin E (MMAE). The in vitro actions and mechanisms of cytotoxicity were assessed using cell viability, immunofluorescence, flow cytometry, and Western blot analysis. In vivo efficacy was determined using an intratibial xenograft mouse model of human prostate cancer and live animal imaging. The half maximal inhibitory concentration (IC50) of MMAE and MMAEp was determined to be approximately 2 and 48 nM, respectively, in PC-3 and C4-2B cell lines. MMAEp retained the mechanism of action of MMAE in reducing microtubule polymerization and stalling cell cycle progression at the G2/M transition. MMAEp was able to bind hydroxyapatite in in vitro assays. MMAEp significantly reduced intratibial tumor growth compared to the vehicle control treatment.

MMAEp is an antimitotic compound that binds to calcium ions in the bone and inhibits prostate tumor growth in the bone. Prostate 76:1420-1430, 2016. © 2016 Wiley Periodicals, Inc.

Is axial shape of distal femur different in normal and osteoarthritic female patients?

This study aims to investigate whether the axial shape of the distal femur is different between normal and osteoarthritic female knees using statistical shape analysis. A total of 126 knee magnetic resonance images of 126 female patients were examined in this study conducted between May 2013 and May 2014. Patients were divided into two groups as study and control groups. The study group consisted of 41 patients (median age 65 years; min. 36 - max. 88 years) who were determined to have knee osteoarthritis, while the control group consisted of 85 patients (median age 43 years; min. 20 - max. 81 years) without knee osteoarthritis. Anatomic and constructive landmarks were selected and marked on each two-dimensional digital image in the axial section of the distal femur. The mean axial shapes of the distal femur were compared between the groups by statistical shape analysis. Shape deformations were investigated by thin plate spline analysis. There were significant differences between the groups regarding the axial shape of the distal femur. Maximal deformation was observed in the femoral notch area.

This study showed that there are deformations in the axial shape of the distal femur in female patients with knee osteoarthritis. Further studies are required to determine whether these differences are important for implant design and surgical technique of total knee replacement.

Does total body fat influence maximal aerobic capacity?

The objective of this study was to examine the influence of body weight and body composition on aspects of aerobic fitness. Our hypothesis was that increased body weight, specifically increased fat mass (FM), would not limit VO2max relative to fat-free mass (FFM), but would reduce maximal and sub-maximal VO2max relative to body weight. We used data from two ongoing studies. In Study 1 a cross-sectional analysis of 129 children across a wide spectrum of body composition was performed. In Study 2 we examined data from 31 overweight women before and after weight loss. VO2max was measured using a treadmill test. Sub-maximal aerobic capacity was evaluated with respiratory exchange ratio (RER), heart-rate (HR), and oxygen uptake relative to VO2max at a given workload (%VO2max). Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Study 1) and a four-compartment model (Study 2). In Study 1, FFM was the strongest determinant of VO2max (r=0.87; P<0.0001). After adjusting for FFM, there was no significant influence of FM on VO2max. After separating children into lean and obese sub-groups, absolute VO2max was significantly higher in the obese (1.24+/-0.27 vs 1.56+/-0.40) and VO2max relative to body weight was significantly lower (44.2+/-3.2 vs 32.0+/-4.1 ml/(kg-min)), whereas there was no significant difference when expressed relative to FFM (57.9+/-5.8 vs 59.2+/-4.9 ml/(kgFFM-min)). Sub-maximal aerobic capacity was significantly lower in the obese children, as indicated by a higher HR and %VO2max; time to exhaustion was significantly lower in the obese children (15.3+/-2.9 vs 11.1+/-2.1 min). In Study 2, FFM was also the strongest determinant of VO2max before and after weight loss. The relationship between VO2max and FFM was identical before and after weight loss so that VO2max relative to FFM was identical before and after weight loss (43.8+/-4.9 vs 45.5+/-6.4 ml/(kgFFM-min)). However, sub-maximal aerobic capacity was lower in the obese state, as indicated by a significantly higher RER (0.85+/-0.06 vs 0.79+/-0.05), HR (124+/-14 vs 102+/-11 bpm), and %VO2max (44% vs 36%).

The major influence of body weight on VO2max is explained by FFM; FM does not have any effect on VO2max. Fatness and excess body weight do not necessarily imply a reduced ability to maximally consume oxygen, but excess fatness does have a detrimental effect on submaximal aerobic capacity. Thus, fatness and VO2max should be considered independent entities.

Does liposomal temocene ( m-THPPo ) photodynamic treatment induce cell death by mitochondria-independent apoptosis?

The cell death pathway activated after photodynamic therapy (PDT) is controlled by a variety of parameters including the chemical structure of the photosensitizer, its subcellular localization, and the photodynamic damage induced. The present study aims to characterize a suitable m-THPPo liposomal formulation, to determine its subcellular localization in HeLa cells and to establish the cell death mechanisms that are activated after photodynamic treatments. Liposomes containing m-THPPo were prepared from a mixture of DPPC and DMPG at a 9:1 molar ratio. In order to procure the best encapsulation efficiency, the m-THPPo/lipid molar ratio was considered. HeLa cells were incubated with liposomal m-THPPo and the subcellular localization of m-THPPo was studied. Several assays such as TUNEL, annexin V/propidium iodide and Hoechst-33258 staining were performed after photodynamic treatments. The apoptotic initiation was assessed by cytochrome c and caspase-2 immunofluorescence. m-THPPo encapsulated in liposomes showed a decrease of the fluorescence and singlet oxygen quantum yields, compared to those of m-THPPo dissolved in tetrahydrofuran. Liposomal m-THPPo showed colocalization with LysoTracker® and it induced photoinactivation of HeLa cells by an apoptotic mechanism. In apoptotic cells no relocalization of cytochrome c could be detected, but caspase-2 was positive immediately after photosensitizing treatments.

Photodynamic treatment with liposomal m-THPPo leads to a significant percentage of apoptotic morphology of HeLa cells. The activation of caspase-2, without the relocalization of cytochrome c, indicates a mitochondrial-independent apoptotic mechanism.

Is cumulative exposure to nucleoside analogue reverse transcriptase inhibitors associated with insulin resistance markers in the Multicenter AIDS Cohort Study?

To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls. Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003. Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 x 1/[log10(glucose) + log10(insulin)] and fasting hyperinsulinemia (insulin > 15 microU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus. Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.13) and a lower QUICKI (-0.04; 95% CI, -0.07 to -0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2-1.3).

Fasting surrogate markers suggest increased insulin resistance in HIV-infected men, which is related to cumulative NRTI exposure.

Do fluctuations of Hyperglycemia and Insulin Sensitivity Are Linked to Menstrual Cycle Phases in Women With T1D?

Factors influencing glycemic variability in type 1 diabetes (T1D) may play a significant role in the refinement of closed loop insulin administration. Phase of menstrual cycle is one such factor that has been inadequately investigated. We propose that unique individual patterns can be constructed and used as parameters of closed loop systems. Women with T1D on continuous subcutaneous insulin infusion and continuous glucose monitoring were studied for 3 consecutive menstrual cycles. Ovulation prediction kits and labs were used to confirm phase of menstrual cycle. Glycemic risks were assessed using the low- and high blood glucose indices (LBGI and HBGI). Insulin sensitivity (SI) was estimated using a Kalman filtering method from meal and insulin data. Overall change significance for glycemic risks was assessed by repeated measures ANOVA, with specific phases emphasized using contrasts. Ovulation was confirmed in 33/36 cycles studied in 12 subjects (age = 33.1 ± 7.0 years, BMI = 25.7 ± 2.9 kg/m(2), A1c = 6.8 ± 0.7%). Risk for hyperglycemia changed significantly during the cycle (P = .023), with HBGI increasing until early luteal phase and returning to initial levels thereafter. LBGI was steady in the follicular phase, decreasing thereafter but not significantly. SI was depressed during the luteal phase when compared to the early follicular phase (P ≤ .05). Total daily insulin, carbohydrates, or calories did not show any significant fluctuations.

Women with T1D have glycemic variability changes that are specific to the individual and are linked to phase of cycle. An increased risk of hyperglycemia was observed during periovulation and early luteal phases compared to the early follicular phase; these changes appear to be associated with decreased insulin sensitivity during the luteal phase.

Do oral contraceptives modify DNA methylation and monocyte-derived macrophage function?

Fertile women may be encouraged to use contraception during clinical trials to avoid potential drug effects on fetuses. However, hormonal contraception interferes with pharmacokinetics and pharmacodynamics and modifies internal milieus. Macrophages depend on the milieu to which they are exposed. Therefore, we assessed whether macrophage function would be affected by the use of combined oral contraceptives (OCs) and if this influence depended on the androgenic or non-androgenic properties of progestin. Healthy adult women were enrolled and stratified into two groups: women who did not use OCs (Fs) and women treated with OCs (FOCs). FOCs were further stratified as a function of androgenic (FOCA+) and non-androgenic (FOCA-) properties of progestins. Routine hematological, biochemical, inflammatory and endothelial dysfunction parameters were measured. Monocyte-derived macrophages (MDMs) were evaluated for the expression and activity of estrogen receptors and androgen receptors, and release of tumor necrosis factor α (TNFα) was measured from unstimulated and lipopolysaccharide-stimulated cells. As is already known, the use of OCs changed numerous parameters: the number of lymphocytes, iron levels, total iron-binding capacity of transferrin, triglycerides, high-density lipoprotein, total cholesterol, and C-reactive protein increased, while prothrombin time and alkaline phosphatase decreased. Hormonal levels also varied: cortisol was higher in FOCs, while luteinizing hormone, follicle-stimulating hormone, and testosterone were lower in FOCs. Asymmetric dimethylarginine, an index of endothelial function, was lower in FOC than in Fs, as were cysteine and bilirubin. The androgenic properties of progestins affected the activity of OCs: in particular, white blood cell count, hemoglobin, high-density lipoprotein and calcium were higher in FOCA- than in FOCA+, whereas percentage oxygen saturation and γ-glutamyl transpeptidase were lower in FOCA- than in FOCA+. Importantly, FOCs had a lower global DNA methylation, indicating that OC may have epigenetic effects on gene expression. OC did not modify the expression of androgen receptor but increased estrogen receptor α expression, more considerably in FOCA+, and decreased estrogen receptor β, more considerably in FOCA-. Importantly, the activation state of estrogen receptor β in FOCs was decreased, while estrogen receptor α was not active in either Fs or FOCs. Unstimulated MDMs obtained from FOCs showed higher release of TNFα in comparison with Fs. After lipopolysaccharide stimulation, the release of TNFα was significantly higher in Fs than in FOCs.

OC use induced many changes in hematological and plasmatic markers, modifying hormonal levels, endothelial function, inflammation index and some redox state parameters, producing a perturbation of the internal milieu that impacted macrophagic function. In fact, different levels of estrogen receptor expression and release of TNFα were observed in macrophages derived from OC users. Some of the above activities were linked to the androgenic properties of progestin. Even though it is not known whether these effects are reversible, the results indicate that to avoid potential skewing of results only a single type of OC should be used during a single clinical trial.

Do hepatectomised patient sera promote hepatocyte differentiation of human-induced pluripotent stem cells?

Human induced pluripotent stem cells, which can be differentiated into hepatocyte-like cells, could provide a source for liver regeneration and bio-artificial liver devices. However, the functionality of hepatocyte-like cells is significantly lower than that of primary hepatocytes. To investigate whether serum from patients undergoing hepatectomy might promote differentiation from human induced pluripotent stem cells to hepatocyte-like cells. Serum from patients undergoing hepatectomy (acquired pre-hepatectomy and 3 hours, 1 day and 3 days post-hepatectomy) was used to replace foetal bovine serum when differentiating human induced pluripotent stem cells into hepatocyte-like cells. Properties of hepatocyte-like cells were assessed and compared with cells cultured in foetal bovine serum. The differentiation efficiency and functionality of hepatocyte-like cells cultured in human serum 3 hours and 1 day post-hepatectomy were superior to those cultured in foetal bovine serum and human serum pre-hepatectomy. Human serum 3 days post-hepatectomy had an equal effect to that of human serum pre-hepatectomy. Some cytochrome P450 isozyme transcript levels of hepatocyte-like cells cultured in human serum were higher than those cultured in foetal bovine serum.

Human serum, particularly that acquired relatively soon after hepatectomy, can enhance the differentiation efficiency and functionality of hepatocyte-like cells derived from human induced pluripotent stem cells.

Do pediatric trauma nurse practitioners provide excellent care with superior patient satisfaction for injured children?

Work hour restrictions for house staff have forced a reevaluation of the traditional roles of all health care providers. In 2001, our level I pediatric trauma center augmented the role of our trauma pediatric nurse practitioners (PNPs) to include in-patient management. We hypothesized that a PNP can provide injured children a level of care commensurate with a resident (RES). All children between 2 months and 17 years old admitted to the Trauma Service were considered for the study. Patients were randomized to PNP or RES care groups. Types of injuries, injury severity score, missed injuries, readmissions, hospital length of stay (LOS), and cost were recorded. Satisfaction surveys were administered to all families. A total of 76 children were enrolled. During the study period, there were no missed injuries or readmissions. The PNP group had a significantly shorter LOS and received significantly higher satisfaction survey scores with regard to information on injuries, tests and treatment, and frequency of visits provided to the patient/family.

PNPs provide equivalent care for injured children with significantly shorter LOS and higher patient satisfaction than RESs. In-patient trauma nurse practitioners provide added value to the care of the injured child in the era of reduced RES work hours.

Does hyaluronan-induced cyclooxygenase-2 expression promote thromboxane A2 production by renal cells?

Matrix degradation products such as fragmented hyaluronan (HA) display important proinflammatory effects on renal tubular epithelial cells (TECs) and macrophages (MPhis). We hypothesized that HA could up-regulate cyclooxygenase type 2 (COX-2) in these cells and that the subsequent production of thromboxane A2 (TXA2) could play a role in inflammatory renal lesions. We used an in vitro approach to examine the expression of COX-1 and COX-2 and the production of TXA2 in response to fragments of HA. COX-2 mRNA, protein, and the resulting TXA2 production were measured in CD44-positive, HA-responsive cells lines of TECs and MPhi. COX-2 mRNA was also measured in vivo in MRL-Faslpr mice and in mice with anti-glomerular basement membrane (anti-GBM) nephritis. In TECs and MPhis, HA increased the steady-state COX-2 mRNA and protein levels markedly, whereas COX-1 mRNA levels did not change. The HA-induced response was comparable to lipopolysaccharide stimulation. In comparison with MPhi, the response was much weaker in TECs. Likewise, the production of TXA2 in response to HA was markedly increased in MPhi, but less in TECs. In TECs and in MPhi, the HA-stimulated TXA2 synthesis was inhibited with the COX-2-selective inhibitors SC58125 (12.5 micromol/L) or celecoxib (0.25 to 5.00 micromol/L). COX-2 mRNA levels were increased in nephritic mice with MRL-Faslpr lupus nephritis and in mice with anti-GBM disease.

HA is a proinflammatory factor that stimulates COX-2 expression and subsequent TXA2 production. Since HA accumulates markedly in renal injury, we speculate that this matrix molecule could therefore play a significant role in thromboxane-mediated immune events in the kidney.

Does antifertility activity of Artemisia vulgaris leave on female Wistar rats?

To evaluate the antifertility activity of Artemisia vulgaris leaves on female Wistar rats. The plant extract was tested for its effect on implant formation at two dose levels, 300 and 600 mg·kg⁻¹, respectively. The effective methanolic plant extract was further studied for estrogenic potency on ovariectomised immature female Wistar rats. The data presented in this study demonstrate the antifertility potential of Artemisia vulgaris methanolic leaf extract, which shows a strong and significant decrease in implant formation (100%), and a strong estrogenic effect resulting in a significant increase in uterine weight in immature ovariectomised rats. These observations suggest that the methanolic extract of Artemisia vulgaris leaves has strong anti-implantation activity and estrogenic activity.

The methanolic plant extract of A. vulgaris has antifertility activity.

Do patients with alcohol dependence respond to placebo?

The purpose of this study was to examine the nature of the effect of placebo medication plus accompanying medical management in the treatment of alcohol dependence. The National Institute on Alcohol Abuse and Alcoholism COMBINE (Combining Medications and Behavioral Interventions) study, a randomized controlled double-blind trial of 1,383 alcohol-dependent patients, compared combinations of medications (acamprosate [Campral] and naltrexone [ReVia]) and behavioral therapy (medical management and specialist-delivered behavioral therapy) for alcohol dependence. This report focuses on a subset of that study population (n = 466) receiving (1) specialized behavioral therapy alone (without pills), (2) specialized behavioral therapy + placebo medication + medical management, or (3) placebo + medical management. During 16 weeks of treatment, participants receiving behavioral therapy alone had a lower percentage of days abstinent (66.6%) than did the participants receiving placebo and medical management (73.1%) or those receiving specialized behavioral therapy + placebo + medical management (79.4%). The group receiving behavioral therapy alone relapsed to heavy drinking more often (79.0%) than those receiving behavioral therapy + placebo + medical management (71.2%). This report focuses on potential explanations for this finding. The two groups of participants receiving placebo + medical management were more likely to attend Alcoholics Anonymous meetings during treatment (32.7% and 32.0% vs 20.4%) and were less likely to withdraw from treatment (14.1% and 22.9% vs 29.3%).

There appeared to be a significant "placebo effect" in the COMBINE Study, consisting of pill taking and seeing a health care professional. Contributing factors to the placebo response may have included pill taking itself, the benefits of meeting with a medical professional, repeated advice to attend Alcoholics Anonymous, and optimism about a medication effect.

Can pharmacy data improve prediction of hospital outcomes?

The performance of comorbidity measures derived from the hospital discharge abstract, the outpatient pharmacy record, and from both sources combined, were compared in predicting all-cause and unplanned hospital readmission and length of stay. Automated hospital and pharmacy data came from Kaiser-Permanente and included 6721 acute hospitalizations in Southern California from April 1993 to February 1995. The Deyo adaptation of Charlson's 17 comorbidities was derived from hospital discharge data and the 29 Chronic Disease Score (CDS) comorbidity markers were derived from outpatient pharmacy claims data. Logistic and OLS regression models were used to compare the performance of each measure in baseline models and to evaluate whether the CDS contributed additional explanatory power in a combined model. The CDS was a significant predictor of unplanned readmission (C = 0.68) and LOS (Adjusted R(2) = 0.26) in multivariable models adjusted for baseline patient demographic and hospitalization characteristics. The Deyo measure was a significant predictor of all-cause readmission (C = 0.63), unplanned readmission (C = 0.68), and LOS (Adjusted R(2) = 0.26). When pharmacy-based disease markers were added to the Deyo baseline model, modest, statistically significant improvements in predictive power were noted in the unplanned readmission and LOS models.

The finding that both measures of comorbid disease demonstrated similar predictive power is noteworthy, because secondary diagnosis data document relevant illness in hospital patients and pharmacy claims data were never intended for that purpose. The results suggest that small improvements in model performance may come from combining both sources of data in models to predict hospital readmission and LOS.

Do early simultaneous fundus autofluorescence and optical coherence tomography features after pars plana vitrectomy for primary rhegmatogenous retinal detachment?

To describe fundus autofluorescence and optical coherence tomography (OCT) features of the macula after pars plana vitrectomy for rhegmatogenous retinal detachment. Thirty-three eyes of 33 consecutive patients with repaired rhegmatogenous retinal detachment with or without the involvement of the macula were prospectively investigated with simultaneous fundus autofluorescence and OCT imaging using the Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany) within a few weeks after the operation. Fundus autofluorescence imaging of the macula showed lines of increased and decreased autofluorescence in 19 cases (57.6%). On OCT, these lines corresponded to the following abnormalities: outer retinal folds, inner retinal folds, and skip reflectivity abnormalities of the photoreceptor inner segment/outer segment band. Other OCT findings, not related to abnormal lines on fundus autofluorescence, consisted of disruption of photoreceptor inner segment/outer segment band and collection of intraretinal or subretinal fluid. The presence of outer retinal folds significantly related to metamorphopsia but did not relate to poor postoperative visual acuity.

Partial-thickness retinal folds occur commonly after vitrectomy for rhegmatogenous retinal detachment repair and may represent an important anatomical substrate for postoperative metamorphopsia. Fundus autofluorescence and OCT are both sensitive techniques for the detection of these abnormalities.

Is decision making by methamphetamine-dependent subjects associated with error-rate-independent decrease in prefrontal and parietal activation?

One important aspect in decision making is how success or failure influences the selection of a response. In a previous investigation, methamphetamine-dependent subjects (MD) selected win-stay/lose-shift consistent responses than normal comparison subjects (NC), which may imply that MD are more influenced by success. This study examined whether the degree of success and the degree of predictability differentially affected MD's decision making. Using functional magnetic resonance imaging, 14 MD were compared with 14 NC while performing the two-choice prediction task at three success rates and the two-choice response task. The increase in win-stay/lose-shift consistent responses by MD relative to NC was independent of success rate. Irrespective of success, MD showed less task-related activation in orbitofrontal cortex (Brodmann's area [BA] 10), dorsolateral prefrontal cortex (BA 9), anterior cingulate (BA 32), and parietal cortex (BA 7). Whereas NC showed success-related patterns of neural activation in the orbitofrontal, dorsolateral prefrontal, and parietal cortex, MD showed activation that was highest when the outcome was most unpredictable.

Our results are consistent with the hypothesis of a more rigid stimulus-response relationship during MD's decision making, which may be due to a shift from processing "success" toward processing the degree of stimulus "predictability."

Are preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 associated with stage progression in papillary thyroid cancer?

Vascular endothelial growth factor (VEGF), a potent angiogenic peptide, and matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme, are found to be abundantly expressed in several types of cancer and correlate with tumour progression. In this study, we investigated the relationship between preoperative plasma VEGF, MMP-9 levels and disease stages in papillary thyroid cancer. Plasma samples were consecutively collected from 30 patients with papillary thyroid cancer preoperatively (seven males and 23 females with a mean age of 45 +/- 16 years) and control plasmas obtained from 30 patients with benign goitre (seven males and 23 females with a mean age of 44 +/- 18 years) and 23 healthy persons (four males and 19 females with a mean age 44 +/- 15 years). Plasma VEGF and MMP-9 concentrations were determined by enzyme-linked immunosorbent assay. Cancer progression was staged by the TNM classification of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). In thyroid cancer patients, the plasma VEGF and MMP-9 values were higher than those in controls (51.8 +/- 11.5 ng/l vs. 27.0 +/- 0.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 22.1 +/- 3.0 micro g/l, respectively; P < 0.05), and those in benign goitre (51.8 +/- 11.5 ng/l vs. 39.7 +/- 8.8 ng/l; 72.3 +/- 23.3 micro g/l vs. 23.0 +/- 2.2 micro g/l, respectively; P < 0.05). But, there was no difference of plasma VEGF and MMP-9 between patients with goitre and normal subjects. A comparison of VEGF and MMP-9 levels in patients at each cancer stage and in patients with benign nodule found that plasma VEGF and MMP-9 values in TNM stages III and IV, but not stage I or II, were significantly elevated (P < 0.05). When cancer patients were grouped according to clinopathological features, the plasma VEGF and MMP-9 concentrations were both significantly elevated in patients with large tumour size (P < 0.01), lymph node involvement (P < 0.01), extrathyroidal invasion (P < 0.05), distant metastasis (P < 0.05) or advanced stages (P < 0.01).

Our study demonstrated that circulating VEGF and MMP-9 levels correlated with progression of papillary thyroid cancer, suggesting plasma VEGF and MMP-9 may serve as preoperative adjuvant markers for assessing disease activity in papillary thyroid cancer. However, they should not be used as a diagnostic tool for differentiating malignant from benign thyroid disorders.

Does self-reported adherence support patient preference for the single tablet regimen ( STR ) in the current cART era?

To analyze self-reported adherence to antiretroviral regimens containing ritonavir-boosted protease inhibitors, nonnucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc. Overall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self-report questionnaire was filled in. Patients were defined as "nonadherent" if reporting one of the following criteria: <90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV-RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence. At the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV-RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis-in-die regimens, while 50.5% were on OD regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The nonadherence proportion was lower in NNRTI than in boosted-PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34-0.94) and the STR (OR: 0.45, 95% CI: 0.22-0.92) reported lower nonadherence. Efavirenz regimens were also associated with lower nonadherence (OR: 0.42, 95% CI: 0.21-0.83), while atazanavir/ritonavir regimens were associated with higher nonadherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV-RNA, and older age were also found to be associated with lower nonadherence, while a longer time on combined antiretroviral therapy was related to higher nonadherence.

STR maintains an advantage in improving adherence with respect to other combined antiretroviral therapies, even though new antiretroviral drugs and drug classes have become available in recent years.

Do drug interaction studies reveal that simotinib upregulates intestinal absorption by increasing the paracellular permeability of intestinal epithelial cells?

Simotinib hydrochloride (SIM6802), which is a new epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), is often prescribed for cancer patients with comorbidities and has serious adverse effects on gastrointestinal physiology. The drug-drug interactions (DDIs) between simotinib and other drugs in combination and the underlying mechanism of its gastrointestinal toxicity remain unclear. We hypothesized that the DDIs and the gastrointestinal toxicity of simotinib were related to its effects on the permeability of the intestine. To determine the intestinal absorption capacity, pharmacokinetic studies and an in situ loop assay were used. The intestinal permeability was measured by a Caco-2 Transwell model. Real time PCR and Western blots were applied to detecting the expression changes of cell junction genes. Our research demonstrated that simotinib upregulated the absorption of cefaclor, valaciclovir and acyclovir. The increase of non-selective absorption was caused by the low expression of cell junction gene afadin-6 and the increase in paracellular permeability in intestinal epithelial cells after simotinib treatment.

These findings revealed that simotinib upregulated intestinal absorption by increasing the paracellular permeability of intestinal epithelial cells. Our research provides theoretical bases for better formulation of EGFR-TKIs to alleviate adverse gastrointestinal effects and also provides guidance for clinical administration of simotinib.

Is level IIb lymph node dissection always necessary in N1b papillary thyroid carcinoma patients?

Papillary thyroid carcinoma (PTC) patients show a high rate of cervical lymphatic metastasis. However, there are no universal binding guidelines for the extent of lateral cervical lymph node dissection (LND) in such cases. In particular, the need for LND above the spinal accessory nerve (SAN) remains controversial. The present study examined whether level IIb lymph node (LN) dissection is always necessary in PTC patients with lateral cervical LN metastasis. The study prospectively examined 167 PTC patients with lateral cervical LN metastasis who underwent modified radical neck dissection (MRND) in our institution from November 2005 to March 2007. The MRND was bilateral in 24 cases. All patients underwent level II, III, IV, and V LND. Levels IIa and IIb LNs were individually dissected in all cases. All LND was performed using strict leveling criteria by a single operating team. The patterns of lymphatic metastasis and potential risk factors for level IIb LN involvement were evaluated. The most common site of metastasis was level III (80.6% of cases), followed by level IV (74.9%) and II (55.5%). The metastasis rates in level IIa and IIb were 55.5% and 6.8%, respectively; all level IIb LN metastasis was accompanied by level IIa metastasis (p=0.001). In addition, level IIb LN metastasis was found to be associated with the aggressiveness of lymphatic metastasis (i.e., the total number of metastatic LNs) (p<0.0001).

A level IIb LND should be performed when there is clinical or radiological evidence of lymphatic metastasis. In the absence of such evidence, the findings suggest that level IIb LND is not necessary in N1b PTC patients when there is no level IIa LN metastasis, or when the metastasis is not aggressive.

Do low c1-inhibitor levels predict early restenosis after eversion carotid endarterectomy?

Homozygotes for the normal (A) allele of mannose-binding lectin (MBL2) gene have higher risks to develop an early restenosis after eversion carotid endarterectomy (CEA). Activation of the lectin pathway is regulated by C1-inhibitor (C1-INH). The objective of the present study was to determine the predictive value of C1-INH in restenosis after CEA. C1-INH and MBL-associated serine protease-2 (MASP-2) were determined in samples serially taken from 64 patients with CEA, who were followed-up with carotid duplex scan (CDS) examinations for 14 months. MBL2 genotypes were also determined. Patients with >50% restenosis had lower C1-INH levels at 6 weeks (P=0.0052) and at 4 days (P=0.0277) postsurgery. C1-INH levels at 6 weeks correlated inversely with the CDS values at 14 months (r=-0.3415, P=0.0058), but only in MBL2 A/A homozygotes (r=-0.5044, P=0.0015). Patients with low C1-INH levels (C1-INH <115%) had higher CDS values already at 7 months postsurgery. Patients with MBL2 A/A and low C1-INH levels at 6 weeks postsurgery had 13.97 (95% CI:1.95 to 100.21, P=0.0087) times higher risk to develop an early restenosis. Differences in the MASP-2 concentration were not associated with restenosis.

Determining C1-INH levels at 6 weeks postsurgery-together with genotyping of MBL2-might be a useful marker in the identification of patients with high risk for early carotid restenosis.

Is executive dysfunction independently associated with reduced functional independence in heart failure?

To examine the independent association between executive function with instrumental activities of daily living and health behaviours in older adults with heart failure. Executive function is an important contributor to functional independence as it consists of cognitive processes needed for decision-making, planning, organising and behavioural monitoring. Impairment in this domain is common in heart failure patients and associated with reduced performance of instrumental activities of daily living in many medical and neurological populations. However, the contribution of executive functions to functional independence and healthy lifestyle choices in heart failure patients has not been fully examined. Cross-sectional analyses. One hundred and seventy-five heart failure patients completed a neuropsychological battery and echocardiogram. Participants also completed the Lawton-Brody Instrumental Activities of Daily Living Scale and reported current cigarette use. Hierarchical regressions revealed that reduced executive function was independently associated with worse instrumental activity of daily living performance with a specific association for decreased ability to manage medications. Partial correlations showed that executive dysfunction was associated with current cigarette use.

Our findings suggest that executive dysfunction is associated with poorer functional independence and contributes to unhealthy behaviours in heart failure. Future studies should examine whether heart failure patients benefit from formal organisation schema (i.e. pill organisers) to maintain independence.

Is gng12 a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2?

Inflammation plays a central role in many neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are the cells primarily responsible for the inflammatory component of these diseases. Using gene expression profiling, we compared the profile of the neurospecific microglial cell line BV-2 after LPS stimulation to that of a macrophage cell line (J774A.1) stimulated with LPS. A set of 77 genes that were modulated only in microglial cells after LPS stimulation was identified. One gene of interest, Gng12, was investigated further to determine its ability to modify the inflammatory response. Specifically, Gng12 mRNA levels were transiently increased after LPS stimulation. In addition, overall levels of Gng12 mRNA after LPS stimulation were significantly higher in BV-2 cells as compared to macrophage cells.

Modulating Gng12 mRNA levels using RNAi revealed a novel role for the factor in the negative regulation of the overall inflammatory response as based on effects on nitrite and TNFalpha levels. These data suggest that Gng12 is a negative regulator of the LPS response and may be an important factor in the overall inflammatory signaling cascade.

Does proteomic analysis reveal responsive proteins of Vibrio parahaemolyticus on exposure to cationic antimicrobial peptides?

To investigate whether Vibrio parahaemolyticus can sense and directly respond to the presence of cationic antimicrobial peptides (AMPs). We performed proteomic methodologies to investigate the responsive proteins of V. parahaemolyticus on exposure to AMP Q6. Differential expression patterns of the outer membrane, inner membrane and cytoplasmic proteins (OMPs, IMPs and CPs) from the bacteria with or without Q6 treatment were obtained using two-dimensional gel electrophoresis (2-DE). Three OMPs (maltoporin, flagellin and OmpV), two IMPs (ATP synthase F1, alpha subunit; and OmpV) and three CPs (pyruvate dehydrogenase subunit E1, glyceraldehyde-3-phosphate dehydrogenase and inositol-5-monophosphate dehydrogenase) were identified using LC-ESI-Q-TOF MS/MS and Mascot program. Real-time quantitative polymerase chain reaction was also performed to determine the mRNA expression level of the target genes.

Our results suggested that V. parahaemolyticus may directly respond to AMPs through the upregulation of the efflux channel, increased yield of energy, effective repair of damaged membranes and downregulation of carbohydrate and nucleotide metabolism for energy preservation.

Do anti-Jo-1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy?

Previous case series have examined the relationship between anti-Jo-1 antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme-linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti-Jo-1 antibody levels and various disease manifestations of myositis. Serum anti-Jo-1 antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention-to-Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti-Jo-1 antibody levels and organ-specific disease activity in cross-sectional and longitudinal analyses, respectively. Cross-sectional assessment of 81 patients with anti-Jo-1 antibody revealed a modest correlation between the anti-Jo-1 antibody level and the serum creatine kinase (CK) level, as well as muscle and joint disease activity. Correlation coefficients were similar for CK levels (r(s) = 0.38, P = 0.002), myositis VAS (r(s) = 0.36, P = 0.002), and arthritis VAS (r(s) = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti-Jo-1 antibody levels correlated significantly with CK levels (R(2) = 0.65, P = 0.0002), myositis VAS (R(2) = 0.53, P = 0.0008), arthritis VAS (R(2) = 0.53, P = 0.006), pulmonary VAS (R(2) = 0.69, P = 0.005), global VAS (R(2) = 0.63, P = 0.002), and global MITAX (R(2) = 0.64, P = 0.0003).

In this large series of patients with idiopathic inflammatory myopathy, anti-Jo-1 antibody levels correlated modestly with muscle and joint disease, an association confirmed by a custom ELISA using recombinant human Jo-1. More striking associations emerged in a smaller longitudinal subset of patients that link anti-Jo-1 antibody levels to muscle, joint, lung, and global disease activity.

Urine dendritic cells: a noninvasive probe for immune activity in bladder cancer?

To test the hypothesis that dendritic cells (DC), antigen-presenting cells with the potential to stimulate primary T-cell responses, may appear in the urine of patients with bladder cancer, and that their characteristics may reflect those of DC in cancer tissue. Cells from digested tissue of transurethral resection specimens from eight patients and urine from 18 with bladder cancers were analysed using flow cytometry, immunohistochemistry and electron microscopy. Urine samples from 12 patients were also analysed during intravesical bacillus Calmette-Guerin (BCG) therapy. Immature DC positive for major histocompatibility complex class II antigens, negative for markers of other leukocyte lineages and with low levels of co-stimulatory markers, were identified in CD45-positive cells isolated immediately from cancer tissue or amongst cells migrating from tissue fragments after overnight culture. Immature-phenotype DC were also identified in the urine of patients with bladder cancer. Their identity was confirmed by immunohistochemistry and electron microscopy. Using these methods, DC were monitored from the bladder during BCG installation for bladder cancer in 12 patients for a mean of 10 months. Of six patients who developed a recurrence of their bladder cancer over this period, all but one showed a lower percentage of DC in their urine at the end of their initial treatment.

We identified DC in the urine of patients with bladder cancer for the first time. We speculate that variability in the percentage of urinary DC may reflect changes in immunological activity at the tumour site; prospective studies are required to evaluate the relevance of these DC counts and characteristics to clinical outcome.

Is exercise capacity in the heat greater in the morning than in the evening in man?

This study investigated the effect of time of day on endurance exercise capacity in a warm environment. Nine males cycled to exhaustion at 65% .VO2peak in an ambient temperature of 35 degrees C (60% relative humidity) at 0645 h (AM) and 1845 h (PM). Rectal temperature (Tc), skin temperature (Tsk), and heart rate (HR) were recorded and blood and expired air samples collected at rest every 5 min during exercise and during recovery. Time to exhaustion was longer in the AM trial (45.8 +/- 10.7 min) than in the PM trial (40.5 +/- 9.0 min; P = 0.009). Resting Tc was lower in the AM trial and remained lower for the first 25 min of exercise (P < 0.001). Tc was not different between trials at the point of exhaustion (AM = 38.7 +/- 0.9 degrees C, PM = 38.8 +/- 0.6 degrees C; P = 0.847). Tsk followed a similar pattern, being lower at rest (P = 0.003) and during the initial stages of exercise (P < 0.05) in the AM trial but not different at exhaustion (P = 0.896). The rate of rise of Tc tended to be greater in the AM trial (P = 0.052), and the rate of rise of Tsk (P = 0.032) and of body heat content (P = 0.009) was also greater in the AM trial. HR was initially higher in the PM trial, but there was no difference at exhaustion. There were no differences between trials in blood glucose concentration or plasma volume change.

The results of this study suggest that endurance exercise capacity in the heat was significantly greater in the morning than the evening, possibly due to a lower initial Tc.

Does exhaled Acetone Concentration be Related to Hemodynamic Severity in Patients With Non-Ischemic Chronic Heart Failure?

We hypothesized that exhaled acetone concentration (EAC), reflecting altered blood ketone body metabolism and increased acetone exhaust because of pulmonary congestion in heart failure (HF), would correlate with hemodynamic parameters in patients with non-ischemic chronic HF. We prospectively enrolled 102 non-ischemic HF patients with New York Heart Association (NYHA) class I-III. Exhaled breath was collected after an overnight fast. Echocardiography and cardiac catheterization were performed in all patients. We also enrolled 17 control patients without HF. EAC in the HF patients was significantly higher than that in the control patients (median EAC; 0.53 vs. 0.38 ppm, P=0.012). EAC positively correlated with blood total ketone bodies (r=0.454, P<0.001), NYHA class (r=0.489, P<0.001), and plasma B-type natriuretic peptide (r=0.316, P=0.001). Right heart catheterization revealed that EAC significantly correlated with pulmonary capillary wedge pressure (PCWP, r=0.377, P<0.001). Receiver-operating characteristic analysis revealed that EAC >1.05 ppm was associated with PCWP ≥18 mmHg (area under the curve [AUC] 0.726, sensitivity 50%, specificity 89%). EAC was shown to be a comparable diagnostic biomarker for HF to BNP (AUC 0.760, sensitivity 80%, specificity 70%).

EAC may be a novel noninvasive biomarker that correlates hemodynamic severity in non-ischemic chronic HF. (Circ J 2016; 80: 1178-1186).

Does chromogranin A expression correlate with tumour cell type and prognosis in signet ring cell carcinoma of the stomach?

To investigate neuroendocrine (NE) differentiation in gastric signet ring cell carcinoma (SRCC) using chromogranin A (CgA) as an indicator of a well-differentiated NE phenotype and to determine its relationship to cell type, stage and prognosis. 102 SRCCs were categorized into five subtypes according to the predominant cell type in the World Health Organization classification. 38 cases (37.3%) showed focal or diffuse CgA positivity. The positive cells were mostly histiocytoid and eosinophilic SRCC cells and some were classical SRCC cells. Small cell and anaplastic-type SRCC cells were only rarely immunopositive. There was no significant relationship between CgA expression and the extent of invasion or presence of metastasis. However, a significant positive correlation existed between CgA positivity and favourable prognosis, with a tendency for greater positivity to be associated with better overall survival. Multivariate analysis showed expression of CgA to be an independent prognostic factor.

CgA expression is restricted to certain tumour cell types and may help to predict prognosis in gastric SRCCs.

Does retinoblastoma suppressor associated protein 46 ( RbAp46 ) attenuate the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression?

BETA-Catenin plays a critical role in embryonic development and tumorigenesis through its function in cell-cell adhesion and in the Wnt-dependent signaling pathway. Thus, the expression of this important protein is strictly and dynamically regulated. A stable cell line from mammary epithelial cells MCF10AT3B that ectropically expresses the retinoblastoma suppressor (Rb) associated protein 46 (RbAp46) was established, and used Western blot, luciferase and cell growth assays to study the effects of constitutive RbAp46 expression. MCF10AT3B cells expressing recombinant RbAp46 exhibited a decreased rate of cell growth. In RbAp46-expressing cells, betacatenin protein was highly phosphorylated and the steady state levels of beta-catenin protein were significantly decreased. Accordingly, the beta-catenin/TCF nuclear signaling was dramatically reduced in RbAp46 expressing cells. In addition, expression levels of glycogen synthase kinase-3beta (GSK-3beta) were increased in RbAp46 expressing cells.

RbAp46 plays an important role in regulation of beta-catenin expression and the beta-catenin/TCF signaling pathway presumably through regulation of GSK-3beta expression.

Does immunohistochemical detection of MYC protein correlate with MYC gene status in aggressive B cell lymphomas?

MYC gene translocation entails a bad prognosis and a poor response to rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in diffuse large B cell lymphomas (DLBCL), and more intensive chemotherapy regimens could be more effective in those cases. Its evaluation requires cytogenetic or fluorescence in-situ hybridization (FISH) studies, which are expensive and not widely available. The aim of this work was to find an immunohistochemical marker able to be used as a screening tool to identify MYC translocations. Aggressive B cell lymphomas in which MYC status was assessed during their diagnostic work-up between 2007 and 2010 were collected, their immunophenotype was re-evaluated, and were stratified according to the Hans algorithm. Two tissue microarrays were built in order to evaluate MYC protein expression with a commercially available antibody. The study was performed on 56 specimens: nine Burkitt lymphomas (eight translocated), 45 DLBCLs (nine translocated) and two lymphomas with intermediate features (both translocated). Only MYC protein expression detected by immunohistochemistry correlated with MYC translocation. No relationship was seen between MYC gene copies and protein expression.

MYC protein expression detected by immunohistochemistry using a commercially available antibody correlates with MYC gene translocation, and could be used as a screening tool to select those cases in which confirmatory genetic testing is mandatory.

Is asymmetrical fetal growth associated with altered trophoblast apoptotic activity in idiopathic intrauterine growth retardation?

To investigate whether there is difference in trophoblast apoptosis between infants with asymmetrical idiopathic intrauterine growth retardation (IUGR) and those with symmetrical fetal growth appropriate for gestational age (AGA). Data and placentas from 52 singleton term pregnancies with idiopathic IUGR, from which a subgroup of 33 (63.4%) infants with asymmetrical growth and malnutrition was identified using the ponderal index served as a study group. The control group included 60 (86.9%) infants with symmetrical growth, identified by the same criterion among 69 normal singleton pregnancies with AGA. IUGR was defined by birthweight less than the 10th percentile of standard values. Ponderal index value was considered as the measurement of fetal growth proportionality. The proportion of fetal thinness up to ponderal index value was greater in the IUGR group than control (χ(2) = 9.2; P = 0.002). There was no statistically significant difference in the cytotrophoblast proliferation (t = 0.88; P = 0.373), trophoblast expression of the Bcl-2 anti-apoptotic factor (z = 0.66; P = 0.505), total trophoblast apoptotic index (t = 0.45; P = 0.651), as in cytotrophoblast (t = 0.01; P = 0.988) and syncytiotrophoblast apoptotic index (t = 0.34; P = 0.730) between the idiopathic asymmetrical IUGR and control group.

Asymmetry of fetal growth is a result of rather long-term placental nutritive insufficiency in which trophoblasts have a central role. Although being crucial for its functioning, the proliferative and apoptotic trophoblast activity remains unaltered in the placentas from pregnancies with idiopathic IUGR and asymmetrical fetal growth. The results obtained in this study indicate that placental nutritive insufficiency may develop without any deviation in the physiological trophoblast regeneration via apoptosis.

Does simulated ischemia induce renal tubular cell apoptosis through a nuclear factor-kappaB dependent mechanism?

Ischemia-reperfusion injury is a relatively common cause of renal tubular cell death and acute renal failure. While nuclear factor-kappaB has been implicated in the pathophysiology of renal ischemia-reperfusion injury, the effect of nuclear factor-kappaB inhibition on ischemia induced renal tubular cell death remains unknown. Renal tubular cells (LLC-PK1) were exposed to simulated ischemia in the presence or absence of 10 microM. pyrrolidine dithiocarbamate (nuclear factor-kappaB inhibitor). Nuclear factor-kappaB activation (electrophoretic mobility shift assay and immunohistochemistry) and the effect of pyrrolidine dithiocarbamate on nuclear factor-kappaB activation (electrophoretic mobility shift assay) and ischemia induced apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling) were determined. Simulated ischemia induced nuclear factor-kappaB activation and renal tubular cell apoptosis versus controls (mean plus or minus standard error of mean 62 +/- 5.2 versus 0.4 +/- 0.3 apoptotic nuclei per high power field, p <0.05). In contrast, previous cellular exposure to pyrrolidine dithiocarbamate effectively inhibited nuclear factor-kappaB activation and prevented ischemia induced apoptosis (mean 14 +/- 6 apoptotic nuclei per high power field).

Simulated ischemia induces nuclear factor-kappaB intranuclear translocation and activation in renal tubular cells. Furthermore, nuclear factor-kappaB mediates ischemia induced renal tubular cell apoptosis. Further elucidation of the complex role of nuclear factor-kappaB in inflammatory injury may lead to the development of targeted therapeutic strategies that ameliorate ischemic renal injury.

Does epidermal filaggrin deficiency mediate increased systemic T-helper 17 immune response?

Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene (FLG) for increased peripheral Th17 cells is unclear. To study whether mutations in FLG influence the frequency of peripheral Th17 cells. We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4(+) T cells. We evaluated ft/ft mice and wild-type (WT) control mice for interleukin (IL)-17-producing CD4(+) T cells in naive mice and following 2,4-dinitrofluorobenzene (DNFB) challenge. In addition, the T-cell receptor (TCR) Vβ-chain repertoire was analysed by flow cytometry. Human studies showed increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2-week-old ft/ft mice. Moreover, altered TCR Vβ-chain repertoire was found in ft/ft mice when compared with WT mice. An increased frequency of CD4(+) Vβ10(+) T cells producing IL-17 was found in the spleen of adult ft/ft mice when compared with WT mice. Finally, DNFB challenge induced an increased number of Th17 cells in ft/ft mice compared with WT mice.

Deficiency of filaggrin appeared to be a driver of increased peripheral levels of Th17 cells. This increase must be acquired as peripheral Th17 cells were found in adult ft/ft mice but not in 2-week-old ft/ft mice indicating involvement of exogenous factors.

Do different levels of cortical excitability reflect clinical fluctuations in migraine?

In a previous study we demonstrated that high-frequency oscillations (HFOs) elicited by median nerve stimulation are significantly correlated to clinical fluctuations of migraine. We aimed at verifying whether clinical fluctuations and HFO changes are correlated to N20 somatosensory evoked potential (SEP) recovery cycle, which is likely to reflect the functional refractoriness of primary somatosensory cortex neurons. We analysed both HFOs and N20 SEP recovery cycle to paired stimulation in 21 migraine patients and 18 healthy volunteers. Shortened recovery cycle correlated with low-amplitude HFOs as well as with clinical worsening. By contrast, prolonged recovery cycle correlated with enhanced HFOs, as well as with spontaneous clinical improvement.

In our migraine patients the strict relationship between presynaptic HFO amplitude and N20 recovery function suggests that changes of both parameters might be caused by modifications of the thalamo-cortical drive. Our findings suggest that the thalamo-cortical drive during interictal stages could fluctuate from abnormally high to abnormally low levels, depending on mechanisms which reduce cortical excitability in spontaneously improving patients, and increase cortical excitability in spontaneously worsening ones.

Does increased primary resistance to recommended antibiotics negatively affect Helicobacter pylori eradication?

To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate. Ninety-two consecutive H. pylori-positive patients with active peptic ulcer disease were randomly enrolled to receive a 7-day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg [all twice a day (b.i.d.), Group A, n = 46]; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d. (Group B, n = 46) H. pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay. Five patients from each study group were lost to follow up. Both treatments resulted in similar H. pylori eradication rate: 66-60% (per protocol), 59-52% (intention-to-treat) in Groups A and B, respectively (non significant). However, eradication improved to 79% in the absence of H. pylori resistance to clarithromycin or amoxicillin.

Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H. pylori infection. Testing for bacterial resistance may become necessary to improve therapeutic efficacy.

Blood flow assessment by ultrasound-induced destruction of echocontrast agents using harmonic power Doppler imaging: which parameters determine contrast replenishment curves?

To evaluate the feasibility of flow determinations by contrast replenishment using harmonic power Doppler imaging (H-PDI). The application of indicator dilution principles on contrast echocardiography is limited by numerous methodical problems. Recently, a new method was introduced that relies on ultrasound-mediated microbubble destruction and evaluation of the contrast replenishment. Definity, a perfluorocarbon-derived contrast agent under development, was continuously infused into a steady flow phantom and H-PDI registrations were performed within a silicone tube (d = 8 mm). Replenishment interval between destruction and imaging frame was varied from 0.04-2 seconds. Nonlinear curve fitting was performed using an exponential mathematical model. Strong linear correlation between contrast dose and maximum signal intensity as well as between flow and the slope variable beta of the replenishment curve was found for all settings (r>0.96). Maximum signal intensity and contrast replenishment rate were found to be a function of emission power and were significantly influenced by depth and focus position.

The feasibility of flow assessment using replenishment curves obtained by H-PDI was demonstrated. However, in experimental conditions, flow analysis was severely influenced by ultrasound system settings and imaging conditions such as emission power, sound field geometry, and investigation depth. For a clinical use of this promising approach, algorithms that take specific system settings and imaging conditions into account have to be found. Imaging modalities that enable a most homogeneous scan field are best suited for the assessment of contrast replenishment.

Are serum α- and β-carotene concentrations associated with the development of advanced beta-cell autoimmunity in children with increased genetic susceptibility to type 1 diabetes?

This case-control study, comprising 108 case children with advanced beta-cell autoimmunity and 216 matched control children, was nested within the nutrition study of the Type 1 Diabetes Prediction and Prevention (DIPP) birth cohort. Serum α- and β-carotene samples were collected each year from the age of 1 to 6 years. For each case-control group, serum samples were analyzed up to the time of seroconversion in the case children. Associations were studied using a conditional logistic-regression model. Neither serum α- nor β-carotene concentration was significantly associated with the risk of advanced beta-cell autoimmunity. There was marginal evidence (P=0.049) of an inverse association between serum β-carotene concentration and the risk of developing advanced beta-cell autoimmunity at a time closest to seroconversion after adjusting for parental education, maternal age, duration of gestation, diabetes in first-degree relatives, number of earlier deliveries and maternal smoking during pregnancy.

The present study data provided no clear evidence to support an association between serum α- or β-carotene concentration and advanced beta-cell autoimmunity.

Can fluid resuscitation prevent pancreatic necrosis in severe acute pancreatitis?

In previous studies, we have demonstrated that hemoconcentration was an early marker for necrotizing pancreatitis. The aim of the present study was to determine whether fluid resuscitation could prevent pancreatic necrosis among patients with hemoconcentration at the time of admission. Data was pooled from the prior two studies of all patients with necrotizing pancreatitis and interstitial pancreatitis with a hematocrit of>or = 44 on admission. Hematocrit values in necrotizing pancreatitis and interstitial pancreatitis were compared at admission and at 24 h. Statistical analyses were performed using the Wilcoxon rank-sum test. A total of 39 patients satisfied our inclusion criteria, 28 with necrotizing pancreatitis and 11 with interstitial pancreatitis. Patients with necrotizing pancreatitis presented earlier than patients with interstitial pancreatitis (median 18 vs. 38 h, respectively) (p = 0.005). There was no significant difference between the intergroup median hematocrits on admission and at 24 h. All patients with hematocrits that failed to decrease at 24 h developed necrotizing pancreatitis (12/28 with necrotizing pancreatitis vs. 0/11 with interstitial pancreatitis) (p = 0.009). There was no significant difference at 24 h in rehydration among the three groups: 4.0 liters among the 12 patients with necrotizing pancreatitis whose hematocrits increased and 4.5 liters among the 16 whose hematocrits decreased at 24 h, and 4.1 liters among the 11 patients with interstitial pancreatitis (p = 0.81).

Patients who presented early were more likely to have necrotizing pancreatitis than interstitial pancreatitis. While fluid resuscitation was not shown to prevent pancreatic necrosis, all patients with inadequate fluid resuscitation as evidenced by persistence of hemoconcentration at 24 h developed necrotizing pancreatitis.

Do phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria?

Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways for the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways.

Therefore, in addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.

Is tMEM106B expression reduced in Alzheimer 's disease brains?

TMEM106B is a transmembrane glycoprotein of unknown function located within endosome/lysosome compartments expressed ubiquitously in various cell types. Previously, the genome-wide association study (GWAS) identified a significant association of TMEM106B single nucleotide polymorphisms (SNPs) with development of frontotemporal lobar degeneration with ubiquitinated TAR DNA-binding protein-43 (TDP-43)-positive inclusions (FTLD-TDP), particularly in the patients exhibiting the progranulin (PGRN) gene (GRN) mutations. Recent studies indicate that TMEM106B plays a pathological role in various neurodegenerative diseases, including Alzheimer's disease (AD). However, at present, the precise levels of TMEM106B expression in AD brains remain unknown. By quantitative reverse transcription (RT)-PCR (qPCR), western blot and immunohistochemistry, we studied TMEM106B and PGRN expression levels in a series of AD and control brains, including amyotrophic lateral sclerosis, Parkinson's disease, multiple system atrophy and non-neurological cases. In AD brains, TMEM106B mRNA and protein levels were significantly reduced, whereas PGRN mRNA levels were elevated, compared with the levels in non-AD brains. In all brains, TMEM106B was expressed in the majority of cortical neurons, hippocampal neurons, and some populations of oligodendrocytes, reactive astrocytes and microglia with the location in the cytoplasm. In AD brains, surviving neurons expressed intense TMEM106B immunoreactivity, while senile plaques, neurofibrillary tangles and the perivascular neuropil, almost devoid of TMEM106B, intensely expressed PGRN.

We found an inverse relationship between TMEM106B (downregulation) and PGRN (upregulation) expression levels in AD brains, suggesting a key role of TMEM106B in the pathological processes of AD.

Percutaneous intrarenal cyst marsupialization and simultaneous nephrolithotomy in selected patients: killing two birds with one stone?

To assess the safety, feasibility, and efficacy of percutaneous intrarenal cyst marsupialization and simultaneous nephrolithotomy in the management of a renal cyst with ipsilateral calculi in selected patients. Between July 2010 and August 2013, 16 patients (11 men and 5 women; mean age, 51 years) with a solitary posterior or parapelvic renal cyst and ipsilateral calculi underwent percutaneous intrarenal cyst marsupialization and simultaneous nephrolithotomy in our center. Mean cyst size was 6.3 cm (range, 4.2-11.8 cm). Mean stone surface area was 5.8 cm(2) (range, 1.8-12.1 cm(2)). By preoperative computed tomography planning and interoperative ultrasound guidance, the optimal puncture route was selected carefully to marsupialize the cyst and approach the target calyx. The cyst was marsupialized into the collecting system at the dilation process. Subsequently, percutaneous nephrolithotomy was performed in a standard fashion. The mean operative time was 68 minutes (range, 47-93 minutes), and the mean hospital stay was 4 days (range, 3-7 days). A nephrostomy tube and a double-J stent were placed for a prolonged period to ensure the channel remained opened. Nearly complete cyst regression and calculi clearance confirmed by postoperative imaging was achieved in all patients. No intraoperative or postoperative complications in Clavien grading score ≥ 2 were noted during a mean follow-up of 21 months (range, 8-25 months).

In selected patients with a posterior or parapelvic renal cyst and ipsilateral calculi, the percutaneous technique is a safe and effective option through intermediate follow-up.

Is subtle hemorrhagic brain injury associated with neurodevelopmental impairment in infants with repaired congenital heart disease?

Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%).

Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

Is duodenal invasion a risk factor for the early dysfunction of biliary metal stents in unresectable pancreatic cancer?

Although the placement of self-expandable metal stents (SEMSs) has been widely accepted as palliation for distal malignant biliary obstruction, the risk factors for their early dysfunction remain unclear. To identify risk factors for early (<3 months) SEMS dysfunction in unresectable pancreatic cancer. A multicenter retrospective study. Five tertiary referral centers. Patients were included who underwent first-time SEMS placement for distal malignant biliary obstruction caused by pancreatic cancer between April 1994 and August 2010. Rates and causes of early dysfunction were evaluated, and risk factors were analyzed. In all, 317 eligible patients were identified. Covered SEMSs were placed in 82% of patients. Duodenal invasion was observed endoscopically in 37%. The median time to dysfunction was 170 days. The rates of all and early SEMS dysfunction were 55% and 31%, respectively. The major causes of SEMS dysfunction were food impaction and nonocclusion cholangitis (21% each) in early dysfunction and sludge (29%) in nonearly dysfunction. The rate of early dysfunction was 42% with duodenal invasion and 24% without duodenal invasion (P = .001). Early dysfunction caused by food impaction was more frequent in patients with duodenal invasion (10% and 4%, P = .053). Duodenal invasion was a risk factor (odds ratio 2.35; 95% CI, 1.43-3.90; P = .001) in a multiple logistic regression model.

A retrospective design.

Does rye kernel breakfast increase satiety in the afternoon - an effect of food structure?

The structure of whole grain cereals is maintained to varying degrees during processing and preparation of foods. Food structure can influence metabolism, including perceived hunger and satiety. A diet that enhances satiety per calorie may help to prevent excessive calorie intake. The objective of this work was to compare subjective appetite ratings after consumption of intact and milled rye kernels. Two studies were performed using a randomized, cross-over design. Ratings for appetite (hunger, satiety and desire to eat) were registered during an 8-h period after consumption of whole and milled rye kernels prepared as breads (study 1, n = 24) and porridges (study 2, n = 20). Sifted wheat bread was used as reference in both study parts and the products were eaten in iso-caloric portions with standardized additional breakfast foods. Breads and porridges were analyzed to determine whether structure (whole vs. milled kernels) effected dietary fibre content and composition after preparation of the products. Statistical evaluation of the appetite ratings after intake of the different breakfasts was done by paired t-tests for morning and afternoon ratings separately, with subjects as random effect and type of breakfast and time points as fixed effects. All rye breakfasts resulted in higher satiety ratings in the morning and afternoon compared with the iso-caloric reference breakfast with sifted wheat bread. Rye bread with milled or whole kernels affected appetite equally, so no effect of structure was observed. In contrast, after consumption of the rye kernel breakfast, satiety was increased and hunger suppressed in the afternoon compared with the milled rye kernel porridge breakfast. This effect could be related to structural differences alone, because the products were equal in nutritional content including dietary fibre content and composition.

The study demonstrates that small changes in diet composition such as cereal grain structure have the potential to effect feelings of hunger and satiety.

Does a CD200FC immunoadhesin prolong rat islet xenograft survival in mice?

A solubilized form of the CD200 molecule, CD200Fc, has been shown to suppress allograft rejection and development of collagen-induced arthritis in mice. We investigated whether the same molecule could prolong survival of rat islet xenografts. Streptozocin-treated mice, receiving injections with anti-asialo-GM1 antibody, received rat islets ( approximately 400/mouse) under the kidney capsule or injected into the portal vein, along with rapamycin treatment. Thereafter mice received injections of CD200Fc (10 microg/mouse/injection) or control mouse IgG2. Blood glucose was monitored daily. Some mice received additional injections of anti-CD200/-CD200R monoclonal antibodies. Portal vein delivery of islets led to more extended resolution of diabetes than did transplantation under the kidney capsule. CD200Fc further prolonged survival in either case, an effect abolished by anti-CD200 or F(ab')2 anti-CD200R mAbs, but not by whole anti-CD200R (anti-CD200R Ig). Spleen cells taken from CD200Fc-treated mice showed polarization to type-2 cytokine production (interleukin-4, interleukin-10) on restimulation with rat splenocytes in culture, in comparison to cells from control mice (type-1 cytokines, interlulin-2, interferon-gamma).

CD200:CD200R interactions are important in regulating rat islet xenograft survival.

Do initial implant position determines the magnitude of crestal bone remodeling?

The ability to predict the amount of bone remodeling around implants is important for a stable and predictable esthetic result. The purpose of this study was to investigate the amount of radiographic bone remodeling that occurs over time using a one-piece implant system. Twenty-seven patients receiving implants in the maxilla and 15 receiving implants in the mandible were included in the study. All implants were placed with a non-submerged surgical technique with varying locations of the rough-smooth border with respect to the alveolar crest. Clinical exams and radiographs were taken on the day of implant placement, at 6 months, and annually up to 5 years. Linear measurements from digitized radiographs were made from the implant shoulder to the first bone-to-implant contact at all time points. A significant amount of bone remodeling compared to baseline occurred for all implants at the 6-month follow-up visit (1.10 mm), with the remaining time points showing virtually no change (0.1 mm). A relationship was found between the amount of bone remodeling and the location of the rough-smooth border with respect to the alveolar crest. Those implants with the rough-smooth border surgically placed below the crest had, on average, a greater amount of remodeling at 6 months (average 1.72 mm) than implants with the rough-smooth border placed at or near the crest (average 0.68 mm). In both situations, this remodeling: 1) occurred early (within 6 months), 2) reached a similar level, and 3) remained virtually unchanged up through 60 months (0.05 mm).

A physiologic dimension appears to exist between the bone and the implant-crown interface around one-piece implants that is established early and maintained over time. These results are significant because they demonstrate in patients that the magnitude of initial bone remodeling around these one-piece dental implants is dependent on the positioning of the rough-smooth border of the implant in an apico-coronal dimension. Furthermore, the dimension, from the crown-implant interface to the first bone-to-implant contact, is consistent with the formation of a biologic width similar to that found around the natural dentition.

Does loss of elastic fibers cause skin wrinkles in sun-damaged human skin?

Although wrinkling is the most obvious sign of aged skin, the detailed pathomechanism of wrinkle development has not been elucidated. In this study, we investigated the role of elastic fibers in the formation of skin wrinkles. Loss of elastic fibers was measured quantitatively in the facial skins of subjects representing seven decades, and then compared with wrinkle severities. We also investigated whether topical retinoic acid treatment to photoaged human skin can restore destroyed elastic fiber, and the correlation between wrinkle improvement with increase in elastic fibers in RA-treated facial skin. We found a significant correlation between decreases in the length, width, number and total area of oxytalan fibers and wrinkle severity. Furthermore, we found that topical application of retinoic acid (0.025%) to chronically photodamaged skin regenerated and restored elastic fibers, and that there was a significant positive correlation between the amount of newly regenerated elastic fiber and the wrinkle improvement caused by retinoic acid.

Our results provide an objective insight into the role of elastic fibers in skin wrinkle formation by providing a quantitative correlation between changes in oxytalan fibers and the severity of skin wrinkling.

Does altered expression of p120catenin predict poor outcome in invasive breast cancer?

The study focuses on p120catenin, a regulator of cell adhesion, which has previously been described in many malignancies and suggested with a role in invasion and metastatic behaviour. In this study, we investigate the role of altered immunoexpression of p120catenin isoforms in the prognosis of invasive breast cancer (n = 351). We used cDNA microarrays to screen differences in gene expression in invasive breast cancer in general, and between local and metastasized disease particularly. On this basis, we performed p120catenin immunohistochemistry in order to confirm the prognostic value of p120catenin isoforms on tissue microarrays comprising 341 patients from the era of mammographic screening, directed to modern surgical and oncological treatments, and followed-up for maximum of 20 years. In cDNA microarray analysis, p120catenin was discovered down-regulated along with E-cadherin and alpha-catenin. In addition, p120catenin distinguished metastasized breast cancer from local disease. Immunohistochemistry confirmed the value of p120catenin as an independent prognosticator of breast cancer survival. In our results, p120catenin was associated with 3.7-fold risk of breast cancer death in multivariate Cox's regression analyses adjusted for the established prognosticators of breast cancer (p = 0.039). Particularly, the long isoform of p120catenin predicted metastatic disease (p = 0.029).

The present paper is the first report on p120catenin in invasive breast cancer based on a well-characterized patient material with long-term follow-up. We observed altered expression of p120catenin isoforms in invasive breast cancer and, in our material, the decrease in p120 immunoexpression was significantly associated with poor outcome of disease.

Is there a role for leukocyte and CRP measurements in the diagnosis of acute appendicitis in the elderly?

The diagnosis of acute appendicitis is still difficult and the results are unsatisfactory in three particular patient groups: in children, in fertile-age women and in elderly patients. As our population ages, the challenge for expedient diagnosis and intervention in older age groups will become more and more significant. The present study aimed at clarifying the role of leukocyte count and C-reactive protein (CRP) measurements in the diagnosis of acute appendicitis in the elderly. In particular, are there patients with acute appendicitis but unelevated leukocyte count and CRP? Eighty-three consecutive elderly patients underwent appendectomy for suspected acute appendicitis. The mean leukocyte count and CRP value were calculated in patients with an uninflamed appendix (group A) and in those with acute appendicitis (group B). The percentages of patients with: (1) both values unelevated; (2) only leukocyte count elevated; (3) only CRP value elevated; (4) both values elevated were calculated within the groups A and B. There was no statistically significant difference in leukocyte counts or CRP values between patients with an uninflamed appendix (group A) and those with acute appendicitis (group B). When the patients were divided into the four subgroups, the most conspicuous finding was that group B (acute appendicitis, n = 73) contained no patients with both values unelevated.

Although elevated leukocyte count and CRP value cannot effectively establish the diagnosis of acute appendicitis in the elderly, unelevated values exclude it. Accordingly, appendectomy is not recommended to be performed in an elderly patient with unelevated leukocyte count and CRP value, although clinical symptoms and signs indicate acute appendicitis.

Is positive geometric vascular remodeling seen after catheter-based radiation followed by conventional stent implantation but not after radioactive stent implantation?

Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm(3)) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm(3)) compared with low-activity radioactive stent implantation (NIH 21.2 mm(3)) and conventional stent implantation (NIH 20.8 mm(3)) (P:=0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling.

Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting.

Does sevoflurane depress myocardial contractility less than halothane during induction of anesthesia in children?

Cardiovascular stability is an important prerequisite for any new volatile anesthetic. We compared echocardiographically derived indices of myocardial contractility during inhalation induction with sevoflurane and halothane in children. Twenty children were randomized to receive either halothane or sevoflurane for inhalation induction of anesthesia. No preoperative medications were given. Myocardial contractility was evaluated at baseline and at sevoflurane and halothane end-tidal concentrations of 1.0 minimum alveolar concentration (MAC) and 1.5 MAC. There were no differences between groups in patient age, sex, physical status, weight, or height. Equilibration times and MAC multiples of sevoflurane and halothane were comparable. Vital signs remained stable throughout the study. Left ventricular end-systolic meridional wall stress increased with halothane but remained unchanged with sevoflurane. Systemic vascular resistance decreased from baseline to 1 MAC and 1.5 MAC with sevoflurane. Halothane depressed contractility as assessed by the stress-velocity index and stress-shortening index, whereas contractility remained within normal limits with sevoflurane. Total minute stress and normalized total mechanical energy expenditure, measures of myocardial oxygen consumption, did not change with either agent.

Myocardial contractility was decreased less during inhalation induction of anesthesia with sevoflurane compared with halothane in children. Although the induction of anesthesia with sevoflurane or halothane was equally well tolerated, the preservation of myocardial contractility with sevoflurane makes it an attractive alternative for inducing anesthesia in children.

Is the Alma Ata vision of comprehensive primary health care viable?

The 4-year (2007-2011) Revitalizing Health for All international research program (http://www.globalhealthequity.ca/projects/proj_revitalizing/index.shtml) supported 20 research teams located in 15 low- and middle-income countries to explore the strengths and weaknesses of comprehensive primary health care (CPHC) initiatives at their local or national levels. Teams were organized in a triad comprised of a senior researcher, a new researcher, and a 'research user' from government, health services, or other organizations with the authority or capacity to apply the research findings. Multiple regional and global team capacity-enhancement meetings were organized to refine methods and to discuss and assess cross-case findings. Most research projects used mixed methods, incorporating analyses of qualitative data (interviews and focus groups), secondary data, and key policy and program documents. Some incorporated historical case study analyses, and a few undertook new surveys. The synthesis of findings in this report was derived through qualitative analysis of final project reports undertaken by three different reviewers. Evidence of comprehensiveness (defined in this research program as efforts to improve equity in access, community empowerment and participation, social and environmental health determinants, and intersectoral action) was found in many of the cases.

Despite the important contextual differences amongst the different country studies, the similarity of many of their findings, often generated using mixed methods, attests to certain transferable health systems characteristics to create and sustain CPHC practices. These include:1. Well-trained and supported community health workers (CHWs) able to work effectively with marginalized communities2. Effective mechanisms for community participation, both informal (through participation in projects and programs, and meaningful consultation) and formal (though program management structures)3. Co-partnership models in program and policy development (in which financial and knowledge supports from governments or institutions are provided to communities, which retain decision-making powers in program design and implementation)4. Support for community advocacy and engagement in health and social systems decision makingThese characteristics, in turn, require a political context that supports state responsibilities for redistributive health and social protection measures.

Does diabetes care differ by type of chronic comorbidity?

To evaluate the relationship between diabetes care and types of comorbidity, classified by the degree to which their treatment is concordant with that for diabetes. Retrospective cohort study (fiscal year [FY] 2001 to FY 2004) of 42,826 veterans with new-onset diabetes in FY 2003. Veterans were classified into five chronic comorbid illness groups (CCIGs): none, concordant only, discordant only, both concordant and discordant, and dominant. Five diabetes-related care measures were assessed in FY 2004 (guideline-consistent testing and treatment goals for HbA(1c) and LDL cholesterol and diabetes-related outpatient visits). Analyses included logistic regressions adjusting for age, race, sex, marital status, priority code, and interaction between CCIGs and visit frequency. Only 20% of patients had no comorbidities. Mean number of visits per year ranged from 7.8 (no CCIG) to 17.5 (dominant CCIG). In unadjusted analyses, presence of any illness was associated with equivalent or better care. In the fully adjusted model, we found interaction between CCIG and visit frequency. When visits were<7 per year, the odds of meeting the goal of HbA(1c)<8% were similar in the concordant (odds ratio 0.96 [95% CI 0.83-1.11]) and lower in the discordant (0.90 [0.81-0.99]) groups compared with the no comorbidity group. Among patients with>24 visits per year, these odds were insignificant. Dominant CCIG was associated with substantially reduced care for glycemic control for all visit categories and for lipid management at all but the highest visit category.

Our study indicates that diabetes care varies by types of comorbidity. Concordant illnesses result in similar or better care, regardless of visit frequency. Discordant illnesses are associated with diminished care: an effect that decreases as visit frequency increases.

Is musculoskeletal pain associated with a long-term increased risk of cancer and cardiovascular-related mortality?

To test the hypothesis that individuals with regional and widespread pain disorders have an increased risk of mortality. We conducted a prospective cohort study of 4515 adults. Subjects were an age- and sex-stratified sample who had participated in a population study of pain occurrence during 1996. Based on those reports subjects were classified as having no pain, regional pain or widespread pain. All subjects were identified on the National Health Service Central Register and followed up until April 2005, a total of 8.2 yrs, at which time information was obtained on vital status, and if applicable, date and cause of death. The relationship between pain status and subsequent death is expressed as mortality rate ratios with 95% CIs, adjusted for age, gender, ethnicity and practice. A total of 35.2% reported regional pain and 16.9% satisfied criteria for widespread pain. In comparison with those without pain, there was a 20% and 30% increased risk of dying over the follow-up period among subjects with regional and widespread pain, respectively. The specific causes of death in excess were cancer and cardiovascular disease. In addition, the mortality risk from both cancer and cardiovascular deaths was found to increase as the number of pain sites that subjects reported increased.

This study supports a previous observation that persons with regional and widespread pain are at an increased risk of cancer death. Possible mechanisms should be explored.

Do obese older adults report high satisfaction and positive experiences with care?

Obese, older adults often have multiple chronic conditions resulting in multiple health care encounters. However, their satisfaction and experiences with care are not well understood. The objective of this study was to examine the independent impact of obesity on patient satisfaction and experiences with care in adults 65 years of age and older with Medigap insurance. Surveys were mailed to 53,286 randomly chosen adults with an AARP® Medicare Supplement Insurance Plan insured by UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare Insurance Company of New York) in 10 states. Following adjustment for non-response bias, multivariate regression modeling was used to adjust for demographic, socioeconomic and health status differences to estimate the independent impact of weight on satisfaction and experiences with care. Outcome variables included four global and four composite measures of satisfaction and experiences with care. 21.4% of the respondents were obese. Relative to normal weight, obesity was significantly associated with higher patient satisfaction and better experiences with care in seven of the eight ratings measured.

Obese individuals were more satisfied and had better experiences with care. Obese individuals had more office visits and discussions about nutrition, exercise and medical checks. This may have led to increased attentiveness to care, explaining the increase in satisfaction and better experiences with care. Given the high level of satisfaction and experiences with care in older, obese adults, opportunities exist for clinicians to address weight concerns in this population.

Does human TM9SF4 be a New Gene Down-Regulated by Hypoxia and Involved in Cell Adhesion of Leukemic Cells?

The transmembrane 9 superfamily protein member 4, TM9SF4, belongs to the TM9SF family of proteins highly conserved through evolution. TM9SF4 homologs, previously identified in many different species, were mainly involved in cellular adhesion, innate immunity and phagocytosis. In human, the function and biological significance of TM9SF4 are currently under investigation. However, TM9SF4 was found overexpressed in human metastatic melanoma and in a small subset of acute myeloid leukemia (AMLs) and myelodysplastic syndromes, consistent with an oncogenic function of this gene. In this study, we first analyzed the expression and regulation of TM9SF4 in normal and leukemic cells and identified TM9SF4 as a gene highly expressed in human quiescent CD34+ hematopoietic progenitor cells (HPCs), regulated during monocytic and granulocytic differentiation of HPCs, both lineages giving rise to mature myeloid cells involved in adhesion, phagocytosis and immunity. Then, we found that TM9SF4 is markedly overexpressed in leukemic cells and in AMLs, particularly in M2, M3 and M4 AMLs (i.e., in AMLs characterized by the presence of a more or less differentiated granulocytic progeny), as compared to normal CD34+ HPCs. Proliferation and differentiation of HPCs occurs in hypoxia, a physiological condition in bone marrow, but also a crucial component of cancer microenvironment. Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.

Altogether, our study reports for the first time the expression of TM9SF4 at the level of normal and leukemic hematopoietic cells and its marked expression at the level of AMLs displaying granulocytic differentiation.

Does myocardial sympathetic denervation prevent chamber-specific alteration of beta-adrenergic transmembrane signaling in rabbits with heart failure?

The purpose of this study was to assess the effect of myocardial sympathetic denervation on the chamber-specific alteration of beta-adrenergic signaling in left ventricular failure in rabbits. Local abnormalities in sympathetic nerve terminals, including the neuronal reuptake of norepinephrine, are thought to be responsible for the chamber-specific regulation of beta-adrenergic signaling in heart failure. Sixteen rabbits were given 6-hydroxydopamine, 25 mg/kg body weight intravenously on days 1 and 2 and 50 mg/kg intravenously on days 7 and 8. Another 16 rabbits received vehicle. Aortic regurgitation was induced in eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits on day 14. Another eight of the 6-hydroxydopamine-treated and eight of the vehicle-treated rabbits underwent a sham operation. The hearts were excised for biochemical analysis on day 21. Hemodynamic characteristics on day 21 showed left ventricular failure in both the aortic regurgitation groups. The plasma norepinephrine concentration on day 21 was higher in both the aortic regurgitation groups than in the sham groups. The beta-adrenoceptor densities and isoproterenol plus 5'-guanylylimidodiphosphate-, 5'-guanylylimidodiphosphate- and sodium fluoride-stimulated adenylyl cyclase activities were decreased only in the failing left ventricle of the vehicle-pretreated aortic regurgitation group, but in both ventricles of the 6-hydroxydopamine-pretreated aortic regurgitation group. The basal and forskolin-stimulated adenylyl cyclase activities were similar in both the aortic regurgitation groups and in the sham groups.

Sympathetic denervation prevented chamber-specific alterations in beta-adrenergic signaling in acute left ventricular failure. Local loss of sympathetic nerve endings, and especially the defective neuronal norepinephrine reuptake, are likely to be responsible for the chamber-specific alteration of the beta-adrenoceptor-G protein-adenylyl cyclase system in heart failure in rabbits.

Does bi-level Positive Airway Pressure ( BiPAP ) with standard exhalation valve improve maximum exercise capacity in patients with COPD?

Although BiPAP has been used as an adjunct to exercise, little is know about its effect on exercise in COPD. We aimed to evaluate the acute effect of BiPAP delivered with a standard valve (Vision, Respironics), compared to no assist, on exercise capacity in individuals with COPD. Peak exercise workload (WLpeak), dyspnea (Borg), end-expiratory lung volume (EELV), tidal volume (VT), minute ventilation (VE), O2 uptake (VO2), and CO2 production (VCO2) were assessed in 10 COPD patients (FEV1 53 ± 22% pred) during three symptom-limited bicycle exercise tests while breathing i) without a ventilator (noPS), ii) with a pressure support (PS) of 0 cm H2O (PS0; IPAP & EPAP 4 cm H2O) and iii) PS of 10 cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O) on separate days using a randomized crossover design. WLpeak was significantly lower with PS10 (33 ± 16) and PS0 (30.5 ± 13) than noPS (43 ± 19) (p < 0.001). Dyspnea at peak exercise was similar with noPS, PS0 and PS10; at isoload it was lower with noPS compared to PS10 and PS0 (p < 0.01). VT and VE were highest with PS10 and lowest with noPS both at peak exercise and isoload (p < 0.001). EELV was similar at peak exercise with all three conditions. VO2 and VCO2 were greater with PS10 and PS0 than noPS (p < 0.001), both at peak exercise and isoload.

Use of BiPAP with a standard exhalation valve during exercise increases VT and VE at the expense of augmenting VCO2 and dyspnea, which in turns reduces WLpeak in COPD patients.

Does immunohistochemical detection improve the prognostic value of lymphatic and blood vessel invasion in primary ductal breast cancer?

Lymphovascular invasion (LBVI) including lymphatic (LVI) and blood (BVI) vessel invasion is a critical step in cancer metastasis. In breast cancer, the optimal detection method of LBVI remains unclear. This research aimed to compare the prognostic value of different assessments of the LVI and BVI in patients with early breast cancer. The study cohort included 360 patients with a median follow-up of 168 months. LBVI on H&E sections (LBVIH&E) was reviewed centrally and blinded to the pathology report. Immunohistochemical staining for D2-40 and Factor VIII was performed to identify LVID2-40 and BVIFVIII. LBVIH&E, LVID2-40 and BVIFVIII were present in 102 (28%), 127 (35%) and 59 (16%) patients respectively. In node-negative patients (206), LBVIH&E, LVID2-40 and BVIFVIII were present in 41 (20%), 53 (26%) and 21 (10%) respectively. In triple-negative patients (120), LBVIH&E, LVID2-40 and BVIFVIII were present in 35 (29%), 46 (38%) and 16 (13%) respectively. LBVIH&E was significantly associated with tumour recurrence in the whole cohort (P < 0.001), node-negative patients (P = 0.001) and triple-negative patients (P = 0.004). LVID2-40 and BVIFVIII were significantly associated with tumour recurrence in whole cohort, node-negative (all P < 0.001) and triple-negative patients (P = 0.002). In multivariate survival analysis, only LVID2-40 and BVIFVIII were independent predictors of cancer specific survival in the whole cohort (P = 0.023 and P < 0.001 respectively), node-negative patients (P = 0.004 and P = 0.001 respectively) and triple-negative patients (P = 0.014 and P = 0.001 respectively).

Assessment of LVI and BVI by IHC using D2-40 and Factor VIII improves prediction of outcome in patients with node-negative and triple-negative breast cancer.

Does loratadine reduce allergen-induced mucosal output of alpha 2-macroglobulin and tryptase in allergic rhinitis?

Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils.

The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).

Are patient outcomes better for unruptured cerebral aneurysms treated at centers that preferentially treat with endovascular coiling : a study of the national inpatient sample 2001-2007?

Practice patterns vary widely among centers with regard to the treatment of unruptured aneurysms. The purpose of the current study was to correlate outcome data with practice patterns, specifically the proportion of unruptured aneurysms treated with neurosurgical clipping versus endovascular coiling. Using the NIS, we evaluated outcomes of patients treated for unruptured aneurysms in the United States from 2001 to 2007. Hospitalizations for clipping or coiling of unruptured cerebral aneurysms were identified by cross-matching ICD codes for diagnosis of unruptured aneurysm with procedure codes for clipping or coiling of cerebral aneurysms. Mortality and morbidity, measured as "discharge to long-term facility," were evaluated in relation to the fraction of cases treated with coils versus clipping as well as the annual number of unruptured aneurysms treated by individual hospitals and individual physicians. Markedly lower morbidity (P < .0001) and mortality (P = .0015) were noted in centers that coiled a higher percentage of aneurysms compared with the proportion of aneurysms clipped. Multivariate analysis showed that greater annual numbers of aneurysms treated by individual practitioners were significantly related to decreased morbidity (OR = 0.98, P < .0001), while the association between morbidity and the annual number of aneurysms treated by hospitals was not significant (OR = 1.00, P = .89).

Centers that treated a higher percentage of unruptured aneurysms with coiling compared with clipping achieved markedly lower rates of morbidity and mortality. Our results also confirm that treatment by high-volume practitioners is associated with decreased morbidity.

Is mammary tumor development directly inhibited by lifelong n-3 polyunsaturated fatty acids?

Despite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. Experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 PUFA) from marine oils may reduce breast cancer risk, however, findings are equivocal. Thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 PUFA in mammary tumorigenesis. fat-1 Mice, which are capable of endogenous n-3 PUFA synthesis, were bred with mouse mammary tumor virus (MMTV)-neu(ndl)-YD5 mice, an aggressive breast cancer model. The resultant offspring, including novel hybrid progeny, were assessed for tumor onset, size and multiplicity as well as n-3 PUFA composition in mammary gland and tumor tissue. A complementary group of MMTV-neu(ndl)-YD5 mice were fed n-3 PUFA in the diet. Mice expressing MMTV-neu(ndl)-YD5 and fat-1 displayed significant (P<.05) reductions in tumor volume (~30%) and multiplicity (~33%), as well as reduced n-6 PUFA and enriched n-3 PUFA in tumor phospholipids relative to MMTV-neu(ndl)-YD5 control mice. The effect observed in hybrid progeny was similarly observed in n-3 PUFA diet fed mice.

Using complementary genetic and conventional dietary approaches we provide, for the first time, unequivocal experimental evidence that n-3 PUFA is causally linked to tumor prevention.

Is the temporoparietal fascial flap an alternative to free flaps for orbitomaxillary reconstruction?

The temporoparietal fascial flap is a thin, pliable, well-vascularized, locoregional flap that can be a reasonable alternative to traditional free flap reconstruction, but its utility for reconstruction of orbitomaxillary defects is often overlooked. The authors investigated the rationale for and benefits of the use of this flap over free tissue transfer in a well-defined subset of head and neck cancer cases. The records of all patients who underwent temporoparietal fascial reconstruction for orbitomaxillectomy between 1993 and 2008 were reviewed. Demographic data, preoperative plans, operative details, and outcomes were assessed to (1) determine the overall outcomes for the temporoparietal fascial flap and (2) analyze preoperative and intraoperative factors that led to the choice of this flap instead of the originally planned free flap. Nineteen patients (mean age, 56 years) were included in this study. Ten (53 percent) were initially considered for free flap reconstruction. Among them, the principal reasons for electing the temporoparietal fascial flap were (1) smaller-than-anticipated extent of resection, (2) need for coverage of implant or bone or thin prosthesis support, and (3) patient comorbidities. Nine resections (47 percent) involved the orbit alone, two (11 percent) involved the maxilla alone, and eight (42 percent) involved a combination of the two. Five patients (26 percent) received neoadjuvant radiation. Four (21 percent) experienced complications (flap failure, ectropion, enophthalmos with intraoral mesh extrusion, and partial skin graft loss). Mean follow-up time was 36 +/- 27 months.

The temporoparietal fascial flap is a viable alternative to free flaps for orbitomaxillary defects when orbital resection is limited, when obturator reconstruction is desired, or when comorbidities preclude microvascular surgery.