A Comparative Analysis of Dominant Dietary Patterns in Patients with and without Oral Squamous Cell Carcinoma.
As a modifiable risk factor, nutrition plays a pivotal role in the prevention or delay of oral squamous cell carcinoma (OSCC). This study was aimed to investigate and compare the dominant dietary patterns in the patients with and without OSCC. This case-control study evaluated the usual dietary intake of 80 cases and 120 controls during 2019-2020 using the 117-item Food Frequency Questionnaire, with confirmed validity and reliability. Factor analysis was used to detect the dominant dietary patterns. Data analysis was done by SPSS (version 21) using the Chi-square test, ANOVA, logistic regression analysis, and independent t-test (P < 0.05). Three dietary patterns were identified, including the western dietary pattern, health dietary pattern, and traditional dietary pattern. The odds ratio (OR) = 1.181 and confidence interval (CI) = 0.671 and 2.082 were found for the western dietary pattern, OR = 1.087 and CI = 0.617 and 1.914 were detected for the healthy dietary pattern, and OR = 0.846 and CI = 0.480 and 1.491 were reported for the traditional dietary pattern. No significant difference was found between the study groups in the dietary pattern and the risk of disease. This relationship remained insignificant after adjustment for the energy intake and confounding factors. There was no significant relationship between adherence to healthy, traditional, and western dietary patterns and OSCC. Consumption of vegetables and nuts had a protective role against the disease, but risky behaviors such as smoking and alcohol use were directly associated with the incidence of the disease.


Incidence of Major Vascular Injuries with Extreme Lateral Interbody Fusion (XLIF).
Extreme lateral interbody fusions (XLIF) and minimally invasive (MI) XLIF theoretically offer wide access to the lumbar disc space. The theoretical advantages of XLIF include; minimally disturbing surrounding structures (e.g. neural, vascular, soft-tissue), while offering stability. In addition to the well-known increased frequency of neurological deficits attributed to XLIF, here we explored how often major vascular injures occur with XLIF/MI XLIF procedures. In 13 XLIF/MI XLIF studies, we evaluated the frequency of major vascular injuries. The studies citing the different frequencies of vascular injuries associated with XLIF/MI XLIF were broken down into three categories. Of the 5 small and larger case series, involving a total of 6,732 patients (e.g. range of 12 to 4,607 patients/study), the incidence of vascular injuries ranged from 0% (3 studies) up to 0.4%. Three case reports presented major vascular injuries attributed to XLIF/MI XLIF. Two involved the L4-L5 level. The three complications included: one fatal injury, one, a retroperitoneal hematoma with hemorrhagic shock, and one major vascular injury. For the 5 review articles, major vascular complications were just discussed in 2, one study cited 3 specific major vascular injuries (e.g. 1 fatal, 1 life threating, and 1 lumbar artery pseudoaneurysm requiring embolization), while 2 other studies stated the frequency of these injuries was 0.4% for XLIF, and 1.7 % for OLIF (Oblique Lumbar Interbody Fusion). According to 5 small and larger case series, 3 case reports, and 5 review articles, the incidence of major vascular injuries occurring during XLIF/MI XLIF ranges from 0 to 0.03% to 0.4%.


Enterobacterial common antigen biosynthesis in Yersinia pestis is tied to antimicrobial peptide resistance.
Resistance to antimicrobial peptides (AMPs) plays an important role in allowing Yersinia pestis to maintain a successful infection in the flea vector Xenopsylla cheopis . Mutants that are unable to modify lipid A in their outer membrane with aminoarabinose (Ara4N), showed increased sensitivity to AMPs such as polymyxin B (PB), as well as decreased survival in fleas. A deletion mutant of wecE , a gene involved in biosynthesis of enterobacterial common antigen (ECA), also displayed hypersusceptibility to PB in vitro. Additional mutants in the ECA biosynthetic pathway were generated, some designed to cause accumulation of intermediate products that sequester undecaprenyl phosphate (Und-P), a lipid carrier that is also used in numerous other pathways, including for peptidoglycan, O-antigen, and Ara4N biosynthesis. Mutants that accumulate Und-PP-linked intermediates (ECA-lipid II) showed increased susceptibility to PB, reduced Ara4N-modified lipid A, altered cell morphology, and decreased ability to maintain flea infections. These effects are consistent with a model where Y. pestis has a sufficiently limited free Und-P pool such that sequestration of Und-P as ECA-lipid II prevents adequate Ara4N biosynthesis, ultimately resulting in AMP hypersusceptibility.


Choledochoduodenostomy in the management of dilated common bile duct due to choledocholithiasis.
Choledochoduodenostomy (CDD) is the operative procedure for Choledocholithiasis in the presence of a dilated common bile duct (CBD). It has been reported as a most effective treatment of CBD stones than T-tube drainage but is regarded as a obsolete therapeutic method due to fears of higher morbidity, cholangitis, "sump" syndrome etc. This study was done prospectively to assess the aforementioned issues analyzing our two years (July 2009 - June 2011) experience.CDD was performed in 31 patients (22 females and 9 males) with aged 18 - 72 years. CBD stones were the only indications in all patients with 18 (45.1%) patients had cholangitis, 8 (35.4%) had cholecystitis and 5 (19.3%) had biliary colic. Abdominal sonogram revealed dilated CBD with single or multiple calculi. The diameter of CBD varies from 14 - 29mm with stone size being ranged from 10- 26mm.Early post operative complications were seen in 4 (12.9%) patients. Only one patient had recurrent cholangitis presented lately due to intrahepatic stones.CDD is a highly effective treatment for choledocholithiasis in all age group with low morbidity and mortality provided a wide anastomosis is accomplished.


Toxigenic Clostridium difficile in retail packed chicken meat and broiler flocks in northeastern Iran.
This study was designed to evaluate the occurrence of Clostridium difficile in both broiler chicken farms and packed chicken parts sold at market places in Mashhad, the second most popular Islamic pilgrimage city after Mecca in northeastern Iran. The fresh faecal samples were obtained from broiler farms, while the chicken packs were purchased from retail outlets across the city at market places and samples were obtained from the necks, thighs, and wings. The selective culture was used for isolation of C. difficile. Out of 40 pooled fresh faecal and 65 packed chicken samples, 14 (35%) and 10 (15.3%) samples were positive, respectively. Some of the C. difficile isolates from chickens packs (7 out of 10, 70%) and faecal samples (5 out of 14, 36%) were detected as toxigenic (A, B and binary toxins) using molecular identification. From 14 isolates of the faecal samples, five isolates were tcdA and tcdB positive, and none was binary toxin positive. The results of the present study suggest that broiler chickens are a potential source of C. difficile, which may infect humans through contact or consumption of chicken meat, although the significance of food contamination is entirely unclear, the role of poultry products as a potential source of the infection should be investigated.


Screw Fixation of Os Acetabuli: An Arthroscopic Technique.
An os acetabuli (OA) increases the contact area and surface area of the acetabulum and is important to maintain congruity of the hip joint. Thus preservation of this ossicle is important to prevent loss of contact area and ensure containment of the femoral head. We describe an all-arthroscopic approach to the fixation of OA with a compression screw. Initially, the fibrous tissue is debrided between the acetabular rim and the OA, a guidewire is placed through the OA up to the acetabular rim, and a screw is inserted over the wire. Compression of the OA is achieved with bone-to-bone contact. This technique prevents loss of femoral head coverage, reducing the risk of subluxation and subsequent osteoarthritis.


[The use of hydroxyapatite substance for the ostheosynthesis after comminuted thigh fractures].
The surgical tactics was analyzed in 102 patients operated on the comminuted thigh fractures. 95 patients were administered in a state of shock; 48 patients had multiple and combined injuries. All patients were operated on with the use of modern metal constructions. Bone fragments' fixation was performed with the use of splint (n=75) or adaptive ostheosynthesis (n=27), in aggreagation with the "KollapAn" fixation substance. Excellent results were acquired in 64 patients, good - in 25 patients and satisfactory - in 12 patients. The long-term results after the year were obtained in 82 patients. The results of the follow-up coincided with those, achieved in postoperative rehabilitation period.


Imaging regiospecific lipid turnover in mouse brain with desorption electrospray ionization mass spectrometry.
Compartmentalization of metabolism into specific regions of the cell, tissue, and organ is critical to life for all organisms. Mass spectrometric imaging techniques have been valuable in identifying and quantifying concentrations of metabolites in specific locations of cells and tissues, but a true understanding of metabolism requires measurement of metabolite flux on a spatially resolved basis. Here, we utilize desorption ESI-MS (DESI-MS) to measure lipid turnover in the brains of mice. We show that anatomically distinct regions of the brain have distinct lipid turnover rates. These turnover measurements, in conjunction with relative concentration, will enable calculation of regiospecific synthesis rates for individual lipid species in vivo. Monitoring spatially dependent changes in metabolism has the potential to significantly facilitate research in many areas, such as brain development, cancer, and neurodegeneration.


How do NPs make clinical decisions?
The authors conducted a study to explore the process primary care NPs use in making clinical decisions and the factors that influence the process. By delineating the process used by primary care NPs in therapeutic decision making, we can enhance clinical decision making in students and practicing NPs.


Molecular cloning and expression of the duplicated thyroid hormone responsive spot 14 (THRSP) genes in ducks.
Thyroid hormone responsive Spot 14 (THRSP) is suggested as a transcription factor involved in the regulation of adipogenic enzymes by 3 thyroid response elements in the promoter region. In the chicken genome, THRSP gene was identified to duplicate into 2 paralogs, THRSPalpha and THRSPbeta. In the current study, cDNA sequences of the duplicated duck THRSP genes were cloned by real-time PCR and rapid amplification of cDNA ends. Duck THRSPalpha and THRSPbeta were predicted to encode peptides with 133 amino acids, which had 74 and 68% sequence identity at cDNA level, 78 and 74% identity at amino acid level to the chicken counterparts, respectively. A high percentage (73.1%) of G and C nucleotides were found in the 3' untranslated region of duck THRSPbeta cDNA. Although a low similarity of peptide composition was shared between ducks and mammals, and a moderate similarity was shared between ducks and chickens, many predicted properties of THRSP, including the pI, subcellular localization and functional domains seemed to be highly conserved. The present study demonstrated that the duck THRSP gene duplicates into the 2 paralogs as in chickens. Phylogenetic analysis indicated that the duplication for THRSP paralogs appeared to have taken place preceding the chicken-duck split, and the diverging rate between THRSP paralogs seemed faster in the chicken genome than that in the duck genome. Expression analysis by real-time quantitative PCR showed that THRSP paralogs in ducks were more actively transcribed in fat tissues (i.e., s.c. fat and abdominal fat) than in liver, and the mRNA concentrations of THRSPbeta were higher than that of THRSPalpha in liver and s.c. fat.


Role of beta2-microglobulin in the intracellular processing of HLA antigens.
The biosynthesis of HLA-A, -B, and -C antigens was examined in the two lymphoblastoid cell lines DAUDI and RAJI. In RAJI cells the HLA-A, -B, and -C antigen heavy chains become core-glycosylated in the endoplasmic reticulum as evidenced by their sensitivity to endo-H digestion and tunicamycin treatment. Beta2-Microglobulin is present in excess in the endoplasmic reticulum of the RAJI cells and associates with the heavy chain at the time of synthesis of the heavy chain. Pulse-chase experiments demonstrated that the RAJI HLA-A, -B, and -C antigen heavy chains become terminally glycosylated since their changed characteristics included resistance to endo-H digestion, sensitivity to neuraminidase treatment, and incorporation fucose. DAUDI HLA-A, -B, and -C antigen heavy chains are synthesized normally and become core-glycosylated but not terminally glycosylated. Other glycosylated cell surface proteins, like the HLA-DR antigens, display normal glycosylation in DAUDI cells. Therefore it is unlikely that the absence of terminally glycosylated HLA-A, -B, and -C antigen heavy chains is the result of a general defect in the biosynthetic machinery of DAUDI cells. However, DAUDI cells lack the ability to synthesize beta2-microglobulin, the common subunit of all HLA-A, -B, and -C antigens. Therefore, it seems reasonable to conclude that beta2-microglobulin is of importance for intracellular transport of newly synthesized HLA-A, -B, and -C antigens.


Measurement of iron and zinc isotopes in human whole blood: preliminary application to the study of HFE genotypes.
Multi-collector inductively coupled plasma--sector field mass spectrometry was applied to the measurement of Fe and Zn isotopes in human whole blood samples. For the Fe present in the blood of healthy adults, enrichment of the lighter isotopes relative to a standard material was observed, in agreement with earlier studies. The level of fractionation was found to be lower in hemochromatosis patients exhibiting homozygous (C282Y/C282Y) mutation of the HFE gene. On the one hand, this reinforces the hypothesis that Fe fractionation in blood decreases with enhanced dietary absorption. On the other hand, this contradicts predictions made on the basis of determinations of Fe fractionation in blood samples collected from subjects characterized by milder HFE mutations. In healthy subjects, the Zn in blood is depleted in lighter isotopes, consistent with the limited number of prior observations. As for Fe, the Zn isotopic composition exhibited a tendency toward lower levels of fractionation in the blood of subjects with hereditary hemochromatosis with homozygous mutation (C282Y/C282Y) of the HFE gene. The results therefore suggest that both Fe and Zn isotopic signatures in whole blood, at least to some extent, reflect polymorphisms in the HFE gene.


Effects of tetrahydrobiopterin and phenylalanine on in vivo human phenylalanine hydroxylase by phenylalanine breath test.
BH(4) administration results in the reduction of blood phenylalanine level in patients with tetrahydrobiopterin (BH(4))-responsive phenylalanine hydroxylase (PAH) deficiency. The mechanism underlying BH(4) response remains unknown. Here, we studied the effects of BH(4) and phenylalanine on in vivo PAH activity of normal controls using the phenylalanine breath test (PBT) by converting l-[1-(13)C] phenylalanine to (13)CO(2). Phenylalanine oxidation rates were expressed as Delta(13)C ((13)CO(2)/(12+13)CO(2), per thousand) and cumulative recovery rates over 120min (CRR(120), %; total amount of (13)CO(2)/the administered dose of (13)C-phenylalanine). Under physiological conditions of blood phenylalanine, BH(4) administration reduced the Delta(13)C peak from 40.8 per thousand to 21.6 per thousand and CRR(120) from 16.9% to 10.2%. Under high blood phenylalanine conditions, administration of BH(4) increased the Delta(13)C peak from 30.7 per thousand to 46.0 per thousand, while the CRR(120) was similar between phenylalanine (19.9%) and phenylalanine+BH(4) (21.1%) groups. Corrected Delta(13)C and CRR(120) were calculated against serum phenylalanine levels to remove the effects of phenylalanine loading. After BH(4) administration, the corrected Delta(13)C peak increased from 82.7 per thousand to 112.6 per thousand, while the corrected CRR(120) was similar (47.6% and 45.6%). These results indicate that phenylalanine worked as a regulator of in vivo PAH by serving as both a substrate and an activator for the enzyme. Excessive dosages of BH(4) inhibited PAH under normal phenylalanine conditions and activated PAH under conditions of high phenylalanine. The regulation system is therefore designed to maintain phenylalanine levels in the human body. Appropriate BH(4) supplementation must be reviewed in patients with BH(4)-responsive PAH deficiency.


In a Temporally Segmented Experience Hippocampal Neurons Represent Temporally Drifting Context But Not Discrete Segments.
There is widespread agreement that episodic memory is organized into a timeline of past experiences. Recent work suggests that the hippocampus may parse the flow of experience into discrete episodes separated by event boundaries. A complementary body of work suggests that context changes gradually as experience unfolds. We recorded from hippocampal neurons as male Long-Evans rats performed 6 blocks of an object discrimination task in sets of 15 trials. Each block was separated by removal from the testing chamber for a delay to enable segmentation. The reward contingency reversed from one block to the next to incentivize segmentation. We expected animals to hold two distinct, recurring representations of context to match the two distinct rule contingencies. Instead, we found that overtrained rats began each block neither above nor below chance but by guessing randomly. While many units had clear firing fields selective to the conjunction of objects in places, a significant population also reflected a continuously drifting code both within block and across blocks. Despite clear boundaries between blocks, we saw no neural evidence for event segmentation in this experiment. Rather, the hippocampal ensemble drifted continuously across time. This continuous drift in the neural representation was consistent with the lack of segmentation observed in behavior.SIGNIFICANCE STATEMENT The neuroscience literature yet to reach consensus on how the hippocampus supports the organization of events across time in episodic memory. Initial studies reported stable hippocampal maps segmented by remapping events. However, it remains unclear whether segmentation is an artifact of cue responsivity. Recently, research has shown that the hippocampal code exhibits continuous drift. Drift may represent a continually evolving context; however, it is unclear whether this is an artifact of changing experiences. We recorded dCA1 in rats performing an object discrimination task designed to segment time. Overtrained rats could not anticipate upcoming context switches but used context boundaries to their advantage. Hippocampal ensembles showed neither evidence of alternating between stable contexts nor sensitivity to boundaries, but showed robust temporal drift.


Evaluation of patients with Alzheimer's disease before and after dental treatment.
Oral infections may play a role in Alzheimer's disease (AD). Objective To describe the orofacial pain, dental characteristics and associated factors in patients with Alzheimer's Disease that underwent dental treatment. Method 29 patients with mild AD diagnosed by a neurologist were included. They fulfilled the Mini Mental State Exam and Pfeffer's questionnaire. A dentist performed a complete evaluation: clinical questionnaire; research diagnostic criteria for temporomandibular disorders; McGill pain questionnaire; oral health impact profile; decayed, missing and filled teeth index; and complete periodontal investigation. The protocol was applied before and after the dental treatment. Periodontal treatments (scaling), extractions and topic nystatin were the most frequent. Results There was a reduction in pain frequency (p=0.014), mandibular functional limitations (p=0.011) and periodontal indexes (p<0.05), and an improvement in quality of life (p=0.009) and functional impairment due to cognitive compromise (p<0.001) after the dental treatment. Orofacial complaints and intensity of pain also diminished. Conclusion The dental treatment contributed to reduce co-morbidities associated with AD and should be routinely included in the assessment of these patients.


Nurse scholars program.
The Nurse Scholars Program was developed for two reasons: to attract highly qualified students to nursing, and to increase the retention of graduates as they enter employment in local agencies following graduation. Scholars receive dollar 10,000 for each of their junior and senior years and are asked to work for 1 year at the agency for each dollar 10,000 received. Additional monies are set aside to assist graduate and doctoral students through stipends. Scholars are paired with Mentors, nurses selected for their expertise and experience and brought into the "family" of the hospital through special events. Mentors are included in educational activities and related programs. To date, dollar 840,000 has been committed to the program, and data regarding the success of the program are continually being assessed.


Maternal Prepregnancy 5-Hydroxytryptamine Exposure Affects the Early Development of the Fetus.
In recent decades, the increasing incidence of depression has contributed to an increase in the use of serotonergic drugs, such as antidepressants, which predisposes humans to serotonin syndrome. Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. It has been well documented that the development of offspring can be affected by maternal exposure to environmental challenges, such as stress, diseases, or an unhealthy diet during pregnancy. Serotonin, also called 5-hydroxytryptamine (5-HT), is widely expressed in the female reproductive system and plays an important role in the development of follicles and embryos. However, whether the suffering of the mother from serotonin syndrome before pregnancy affects fetal development is still uncertain. In the present study, to explore the effect of maternal prepregnancy 5-HT exposure on the fetus, intraperitoneal injection of 5-HT was used to change maternal prepregnancy 5-HT levels. It was found that maternal prepregnancy 5-HT exposure significantly reduced the body weight and liver weight and the levels of estrogen and progesterone in female mice. Although there was no significant difference in the cleavage rate and blastocyst rate between the 5-HT and control groups, maternal prepregnancy 5-HT exposure increased the percentage of embryo resorption, decreased placental weight, and led to placental inflammation at E13.5. Notably, 5-HT exposure caused weight loss in the offspring at 2 weeks. These results suggested that maternal prepregnancy 5-HT exposure could affect the development of the offspring, which was partly caused by reduced hormonal secretion and placental inflammation.


'One-size doesn't fit all': Understanding healthcare practitioners' perceptions, attitudes and behaviours towards sexual and reproductive health and rights in low resource settings: An exploratory qualitative study.
Although progress has been made to improve access to sexual and reproductive health services globally in the past two decades, in many low-income countries, improvements have been slow. Discrimination against vulnerable groups and failure to address health inequities openly and comprehensively play a role in this stagnation. Healthcare practitioners are important actors who, often alone, decide who accesses services and how. This study explores how health care practitioners perceive sexual and reproductive health and rights (SRHR) and how background factors influence them during service delivery. Participants were a purposefully selected sample of health practitioners from five low income countries attending a training in at Lund University, Sweden. Semi-structured interviews and qualitative content analysis were used. Three themes emerged. The first theme, "one-size doesn't fit all' in SRHR" reflects health practitioners' perception of SRHR. Although they perceived rights as fundamental to sexual and reproductive health, exercising of these rights was perceived to be context-specific. The second theme, "aligning a pathway to service delivery", illustrates a reflective balancing act between their personal values and societal norms in service delivery, while the third theme, "health practitioners acting as gatekeepers", describes how this balancing act oscillates between enabling and blocking behaviours. The findings suggest that, even though health care practitioners perceive SRHR as fundamental rights, their preparedness to ensure that these rights were upheld in service delivery is influenced by personal values and society norms. This could lead to actions that enable or block service delivery.


The reduction clamp: a simple device for closed reduction during intramedullary nailing.
Reduction of femoral shaft fractures prior to passing the guide pin during intramedullary fixation may be a challenging problem, especially in delayed reductions or obese patients. We describe a simple and useful instrument for obtaining and maintaining reduction for closed intramedullary fixation. It provides a three-point fixation that may be locked into position to maintain the reduction. The surgeon is not required to hold the device in position while passing the guide pin, the reamer, or the nail. It frees the surgeon's hands, minimizes the need for an assistant, and reduces harmful x-ray exposure to the hands.


Scattering from suspended sediments having different and mixed mineralogical compositions: comparison of laboratory measurements and theoretical predictions.
Laboratory measurements of the acoustic scattering properties of aqueous suspensions of non-cohesive sands having different and mixed mineralogical compositions are presented. Four different types of sand are examined: quartz, crushed shell, magnetite, and muscovite mica. The experimental data obtained for each type of sand are compared with theoretical scattering predictions for spheres having the same physical properties. The results show that for each type of sand, scattering is enhanced in the geometric regime relative to the sphere predictions, and for mica, scattering in the Rayleigh regime is reduced. To provide a theoretical framework for the observations, the applicability of two different modified sphere scattering models previously reported in the literature is evaluated. Measurements of the ensemble scattering properties obtained from mixtures of the different sands are also presented and compared with theoretical predictions. The results show that to accurately predict the scattering properties of compositionally diverse mixed sediment suspensions, it is necessary to know the relative proportions of each mineral present at each size within the size distribution; however, the scattering properties can be approximated for the suspensions studied by considering only the dominant mineral by mass.


Acute oral toxicities of wildland fire control chemicals to birds.
Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.


Soft tissue sarcomas in agriculture and forestry workers.
The National Cancer Register maintained by the Office of Population Censuses and Surveys (OPCS) was used to investigate the relative risks of soft tissue sarcomas among farmers, agricultural workers, and related occupational groups. The relative risk for the group as a whole was 1.15 (95% confidence limits 0.83-1.59). One of the four subgroups (which comprises farmers, farm managers, and market gardeners) experienced a relative risk of 1.7 which just achieves significance at the 5% level (95% confidence limits 1.00-2.88). The risks in the other three subgroups were respectively 1.0 (agricultural workers, 003), 0.7 (gardeners and groundsmen, 005), and 1.0 (foresters and woodmen, 006). No attempt has been made in this study to determine exposure to phenoxy herbicides in cases or controls. The significance of these findings is discussed.


Inhibition of chondrogenesis by integrin antibody in vitro.
Integrins mediate cell attachment to a variety of extracellular matrix proteins. These interactions play an important role in morphogenesis and differentiation. The mediating functions of integrins during chondrogenesis in vitro were investigated by using mesenchymal cells from limb buds of day 12 mouse embryos. The cells were treated with anti-beta 1, -alpha 1, and -alpha 5 integrin antibodies (a) from day 1 to day 3 and (b) from day 3 to day 7 of cultivation. The total culture period was 7 days. The presence of exogenous anti-beta 1, but not -alpha 1 and -alpha 5 integrin antibodies, from day 1 to 3 completely inhibited the differentiation of blastemal cells to chondroblasts and the formation of cartilage matrix. On the other hand, the presence of exogenous anti-beta 1, -alpha 1, and -alpha 5 integrin antibodies from day 3 of cultivation onwards had no effect. Immunoblotting and immunomorphological findings in the cultures treated with anti-beta 1 antibody from day 1 to day 3 revealed a pattern of integrins and collagen composed of beta 1, alpha 1, alpha 5 beta 1 integrins and collagen type I. The cartilage-specific chondroitin sulfate proteoglycan (CSPG) could not be demonstrated in these cultures. The cultures treated later (day 3 to day 7) showed a pattern of beta 1, alpha 3, alpha 5 beta 1, and alpha v beta 3 integrins, collagen types I and II, and CSPG identical to that of the untreated controls. These findings indicate that beta 1-integrins play a crucial role in early cartilage differentiation and point to a possible important cell-matrix interaction in the induction of chondrogenesis.


High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution.
Nonmyeloablative conditioning is increasingly used for transplantation in a wide range of diseases, but little is known about its impact on the incidence of infections and immune reconstitution. We examined the pattern and outcome of cytomegalovirus (CMV) infections monitored by polymerase chain reaction-based assays and treated preemptively in 101 patients following nonmyeloablative conditioning containing in vivo Campath-1H. Fifty-one patients (50%) had a CMV infection at a median of 27 days after transplantation with a probability of 84.8% in patients at risk of CMV infection. The probability of recurrence of CMV infection before and after 100 days was 53.6% and 46.6%, respectively, and was more common in unrelated donor transplant recipients. All 3 patients who developed CMV disease died of this complication. The 2 patients with late CMV disease had grade III to IV graft-versus-host-disease (GVHD), which occurred de novo in only 4% of patients and in another 10% following donor lymphocyte infusions. The median time to CD4(+) T-cell count more than 200/microL was 9 months in the 48 patients studied. The probabilities of overall survival and nonrelapse mortality at 18 months were 65% and 27.8%, respectively, with no significant difference in survival between CMV-infected and -uninfected patients. The use of Campath-1H appeared to be associated with a low incidence of GVHD but a high incidence of CMV infections and prolonged immune paresis.


Small intestinal manometry in healthy elderly subjects.
Small intestinal manometry was performed on ten healthy elderly subjects (mean age, 72 years) and ten healthy young-adult subjects (mean age 25 years). All three phases of the migrating motor complex were observed in both groups during fasting. There were no differences in the motility index between the two groups, the frequency and the mean amplitude of contractions of phases 2 and 3, or the duration and the velocity of propagation of phase 3. After a meal the motility index and the frequency of contractions were significantly lower (P less than 0.05) in the elderly group. The results suggest that intestinal motility after a meal is less in the elderly than in young adults.


Environmental Specification of Pluripotent Stem Cell Derived Endothelial Cells Toward Arterial and Venous Subtypes.
Endothelial cells (ECs) are required for a multitude of cardiovascular clinical applications, such as revascularization of ischemic tissues or endothelialization of tissue engineered grafts. Patient derived primary ECs are limited in number, have donor variabilities and their in vitro phenotypes and functions can deteriorate over time. This necessitates the exploration of alternative EC sources. Although there has been a recent surge in the use of pluripotent stem cell derived endothelial cells (PSC-ECs) for various cardiovascular clinical applications, current differentiation protocols yield a heterogeneous EC population, where their specification into arterial or venous subtypes is undefined. Since arterial and venous ECs are phenotypically and functionally different, inappropriate matching of exogenous ECs to host sites can potentially affect clinical efficacy, as exemplified by venous graft mismatch when placed into an arterial environment. Therefore, there is a need to design and employ environmental cues that can effectively modulate PSC-ECs into a more homogeneous arterial or venous phenotype for better adaptation to the host environment, which will in turn contribute to better application efficacy. In this review, we will first give an overview of the developmental and functional differences between arterial and venous ECs. This provides the foundation for our subsequent discussion on the different bioengineering strategies that have been investigated to varying extent in providing biochemical and biophysical environmental cues to mature PSC-ECs into arterial or venous subtypes. The ability to efficiently leverage on a combination of biochemical and biophysical environmental cues to modulate intrinsic arterio-venous specification programs in ECs will greatly facilitate future translational applications of PSC-ECs. Since the development and maintenance of arterial and venous ECs in vivo occur in disparate physio-chemical microenvironments, it is conceivable that the application of these environmental factors in customized combinations or magnitudes can be used to selectively mature PSC-ECs into an arterial or venous subtype.


Tumor lysis syndrome associated with chemotherapy in primary retroperitoneal soft tissue sarcoma by ex vivo ATP-based tumor chemo-sensitivity assay (ATP-TCA).
Tumor lysis syndrome (TLS), a result of rapid cell lysis following tumor therapy, is a well recognized complication during the treatment of rapidly growing tumors. TLS rarely occurs in solid tumors. We present a case report of TLS in a patient with primary retroperitoneal soft tissue sarcoma. TLS occurred in the patient after four days' combinational chemotherapy with cisplatin, adriamycin, and dacarbazine. These drugs were selected on the basis of an ex vivo ATP-based tumor sensitivity assay. TLS was properly controlled in the patient with concomitant remission of the sarcoma. Therefore, precautions should be taken to avoid this potentially fatal complication during treatment of solid tumors, especially with tumors highly sensitive to drugs.


Nutritional and functional properties of fishmeal produced from fresh by-products of cod (Gadus morhua L.) and saithe (Pollachius virens).
Fresh by-products of whitefish such as cod and saithe is processed to fishmeal (FM) on-board seagoing Norwegian trawlers. The aim of this study was to document the properties of whitefish FM (WFM) protein with respect to, physicochemical and bioactive properties. Analysis of the proximate composition of representative seasonal WFM batches show that the production is robust without much variance. The mean protein (61.9 ± 1.2), fat (8.9 ± 1.1%), moisture (5 ± 1.2%) and ash content (22.4 ± 0.8%), reflect the use of lean and bony raw-material. The WFM has a low content of free amino acids (0.7%) and biogenic amines (< 1000 mg/kg) that confirm the high quality and freshness of the raw material. Amino-acid analysis identified the presence of all nutritionally essential amino acids. The WFM physicochemical properties was comparable to soy-bean meal (SBM) by analysis of solubility, water-holding capacity (WHC), the emulsion stability (ES). Proteolytic degradation of the WFM was used to demonstrate the presence of bioactive peptides with inhibiting activity against angiotensin-converting enzyme (ACE) activity, in vitro. Taken together, WFM produced from fresh by-products is an excellent protein source with attributes of interest beyond the aquafeed-market.


Investigation of the correlation between internet addiction, obesity risk and sleep disorder in children.
This study was performed with the aim of investigating the correlation and the effective factors between internet addiction, obesity risk and sleep disorders in children. The sample for this descriptive and relational search type study comprised the parents of 458 children aged 7-10 years attending a primary school in Turkey. Data were collected the Parent and Child Descriptive Information Form, Family Child Internet Addiction Scale (FCIAS), Family Nutrition and Physical Activity Tool (FNPAT) and Sleep Disturbance Scale for Children (SDSC). There was a statistically significant, positive and weak correlation between the Body Mass Index (BMI) and FCIAS scores of children (p < 0.001). There was a statistically significant, negative and very weak correlation between FNPAT total score with FCIAS total score (p = 0.007). There was a statistically significant, positive and moderate correlation between SDSC total score and FCIAS total score (p < 0.001). According to regression analysis, FCIAS was a determinant at significant levels for FNPAT and SDSC (p < 0.05). There was a relationship between internet addiction and obesity and sleep quality. As a result of the study, the increase in internet use was determined to negatively impact physical activity and health nutrition behavior, and to increase sleep disturbance. Pediatric nurses are recommended to give counseling to children and families about preventing obesity and the risk of sleep disorders by identifying children at risk in terms of internet addiction in the early period.


Association of insomnia and daytime sleepiness with low back pain: A bidirectional mendelian randomization analysis.
Purpose: Observational research has indicated the presence of a causal relationship between sleep disturbances and low back pain (LBP). However, the link may have been biased by confounding factors. The purpose of this study was to examine the potential causal association of insomnia and daytime sleepiness with LBP by using mendelian randomization (MR). Methods: Genome-wide association study (GWAS) summary statistics of insomnia were obtained from a large-scale GWAS meta-analysis (n = 1,331,010; individuals from UK Biobank and 23andMe) or UK Biobank alone (n = 453,379). The summary statistics of daytime sleepiness were from UK Biobank (n = 452,071) and LBP were provided by the FinnGen Release 6 (210,645 individuals with 16,356 LBP cases and 194,289 controls) or UK Biobank (5,423 cases versus 355,771 controls). Linkage disequilibrium score (LDSC) regression and bidirectional MR analysis was employed to estimate genetic correlation and causal relationship. In the MR analysis, the inverse variance weighted method (IVW) was utilized as the main analysis procedure, while MR-Egger, Weighted median and Robust adjusted profile score (RAPS) were utilized for supplementary analyses. Results: LDSC analysis showed that LBP were significantly genetically correlated with insomnia (rg = 0.57, p = 2.26e-25) and daytime sleepiness (rg = 0.18, p = 0.001). The MR analysis revealed that genetically predicted insomnia was significantly associated with an increased risk of LBP (OR = 1.250, 95% CI: 1.186-1.318; p = 1.69e-16). However, the reverse causality was not confirmed. No evidence was identified supporting causality of daytime sleepiness and LBP. Conclusion: This study demonstrates a putative causal link of insomnia on LBP and a null causal effect of LBP on insomnia. Furthermore, a causal link between daytime sleepiness and LBP were not reported. This finding may stimulate new strategies for patient management in clinical practice, benefiting public health.


Optimization of the design and preparation of nanoscale phospholipid bilayers for its application to solution NMR.
Despite arduous efforts and recent technological developments structural investigation of integral membrane proteins remains a challenge. The primary deterrents include difficulties with their expression, low inherent solubility, and problems associated with existing membrane mimicking systems. A relatively new class of membrane mimetics, nanodiscs, is emerging as a promising alternative. Although nanodiscs have been proven successful for several biophysical applications, they yet remain to become the system of preferred choice for structure determination. We have hereby made nanodiscs more suitable for solution NMR applications by reducing the diameter of the self-assembly complex to its potential limit. We achieved a noticeable improvement in the quality of NMR spectra obtained for the transmembrane and cytoplasmic domains of integrin αIIb incorporated into these smaller discs rendering them susceptible for a thorough structural investigation. In addition, we also present an on-column method for a rapid, efficient, single-step preparation of protein incorporated nanodiscs at high concentrations. These discs have been fully characterized by transmission electron microscopy, dynamic light scattering, and differential scanning calorimetry.


Structural evolution of colloidal gels during constricted microchannel flow.
We investigate the structure of colloidal gels flowing through constrictions in microchannels using confocal microscopy. As the gel traverses the constricted region, both the average velocity and particle density increase downstream. While the average flow profile is smoothly varying, stagnation zones develop at the constriction entry, leading to markedly nonuniform local flow profiles. Dense clusters undergo shear-induced yielding at intercluster boundaries, which enhances the structural heterogeneity of the suspension at the constriction outlet.


Muscarinic supersensitivity in the rat urinary bladder after capsaicin pretreatment.
The effects of capsaicin on urinary bladder function have been investigated in adult rats. Ten days after capsaicin treatment immunocytochemical investigations showed a nearly complete disappearance of substance P (SP) and calcitonin gene-related peptide (CGRP) in all parts of the bladder. Recordings of micturition patterns and cytometrical investigations in conscious animals revealed no functional effects of capsaicin treatment. In-vitro experiments showed that the contractile response to substance P was similar before and after capsaicin treatment and CGRP exerted no contractile effects on the urinary bladder in either group of rats. The concentration-response curve to carbachol as well as the frequency-response curve to electrical stimulation were significantly shifted to the left in bladder muscle after capsaicin treatment. However, the maximal responses were similar in control and capsaicin-treated bladders. In the presence of scopolamine the maximal response to electrical stimulation was clearly lower in bladders subjected to capsaicin treatment than in controls. In conclusion, depletion of substance P and CGRP in the rat urinary bladder by capsaicin induced no supersensitivity to these peptides. However, the increased sensitivity to carbachol and to electrical stimulation seen after capsaicin treatment indicates the development of a supersensitivity to muscarinic receptor stimulation. Despite this supersensitivity in vitro no functional effects of capsaicin treatment were found in vivo.


[HPV vaccination].
Human Papilloma Viruses are associated with genital carcinoma (of the cervix, anus, vulva, vagina and the penis) as well as with non-genital carcinoma (oropharyngeal carcinoma) and genital warts. In Switzerland two highly efficient and safe vaccines are available. The safety of these vaccines has been repeatedly subject of controversial discussions, however so far post marketing surveillance has always been able to confirm the safety. In Switzerland girls and young women have been offered the HPV vaccination within cantonal programmes since 2008. 2015 the recommendation for the HPV-vaccination for boys and young men was issued, and starting July 1, 2016 they as well will be offered vaccination free of charge within the cantonal programmes. This article discusses the burden of disease, efficacy and safety of the vaccines and presents facts which are important for vaccinating these young people. Specifically, aspects of the decisional capacity of adolescents to consent to the vaccination are presented. Finally, the future perspective with a focus on a new vaccine with an enlarged spectrum of HPV-types is discussed.


Comparative research on neural dysfunction in children with dyslexia under different writing systems: A meta-analysis study.
Developmental dyslexia is a special learning disorder which is prevalent in all languages. A central question in dyslexia is whether the neural mechanism of their defects is universal or distinct in different writing systems. Using meta-analytic approach, we created meta-images using activation abnormalities in Chinese and alphabetic children with dyslexia to find convergence and divergence under different writing systems. The results revealed that dyslexic children have a universal attention-related dysfunction with hypoactivation in the left inferior frontal cortex (IFC) and the anterior cingulate cortex (ACC) under different writing systems, in spite of differences of degree and spatial extent in those regions. Alphabetic dyslexic children additionally showed hypoactivation in the left occipito-temporo-parietal regions. Chinese dyslexic children showed specific hyperactivation in the right postcentral gyrus, the left rectus, and the right middle temporal gyrus. The present meta-analysis for the first time showed both shared and distinct abnormalities in children with dyslexia under Chinese and alphabetic writing systems.


Living with lipoedema: reviewing different self-management techniques.
At present, there is no proven cure for lipoedema. Nevertheless, much can be done to help improve symptoms and prevent progression. Many of these improvements can be achieved by patients using self-management techniques. This article describes the range of self-management techniques that community nurses can discuss with patients, including healthy eating, low-impact exercise, compression garments, self-lymphatic drainage, and counselling.


Effect of Acromioplasty on Postoperative Pain Following Rotator Cuff Repair.
Background: The surgical treatment of rotator cuff tears traditionally involves rotator cuff repair (RCR) with concomitant acromioplasty. However, there is some doubt as to whether acromioplasty is of value to this procedure. Questions/Purpose: We sought to evaluate whether RCR with acromioplasty provided better outcomes than RCR without acromioplasty in a cohort of more than 1000 patients. Methods: This retrospective cohort study involved 1320 patients with rotator cuff tears who subsequently received a primary arthroscopic RCR, with acromioplasty (n = 160) or without acromioplasty (n = 1160), performed by a single surgeon. Acromioplasty was performed if there was significant mechanical impingement on the rotator cuff. To assess outcomes, all patients completed a standardized, modified L'Insalata questionnaire in which they reported the level and severity of pain at rest and during activities. An examiner assessed shoulder strength and range of motion before and 1 week, 6 weeks, 12 weeks, and 6 months after surgery. Results: Patients who had RCR with concurrent acromioplasty had a greater level of pain and more frequent pain 1 week after surgery. However, at 6 months there were no differences between patients who underwent RCR with or without acromioplasty in any patient-reported outcome (level of pain with overhead activity, at rest and during sleep; frequency of pain with activity, sleep and extreme pain, difficulty of activity overhead and behind back, level of shoulder stiffness; and overall shoulder satisfaction). The postoperative re-tear rate in both groups was 13%. Conclusion: This study showed no additional benefit to acromioplasty in patients undergoing RCR.


Tracing of fluoro-gold prelabeled microglia injected into the adult rat brain.
In light of a recent interest in the transplantation of cultured microglial cells, we have examined the use of the fluorescent dye Fluoro-Gold (FG) as a tracer for these cells. Following injection into the adult rat brain, FG prelabeled microglial cells were readily traceable for up to 2 weeks with minimal labeling of endogenous cell populations. Some of the injected cells differentiated into ramified microglial cells as a result of exposure to the adult CNS environment. Injection of free FG into the adult rat brain resulted in the widespread labeling of neurons and perivascular cells, but not endogenous microglial cells, indicating that perivascular cells, but not resting microglia, are actively pinocytotic cells of the CNS. Our results show that FG is an effective label for the tracing of transplanted microglial cells.


Predicting outcomes after total knee arthroplasty using intraoperative knee kinematics measured by navigation.
The objective of the study is to evaluate the relationship between clinical results following posterior-stabilized total knee arthroplasty (TKA) and intraoperative kinematic pattern determined from navigation. Participants were patients with knee osteoarthritis and varus deformity who underwent primary posterior-stabilized TKA. Preoperative and post-implantation kinematic data were recorded, and all kinematic patterns were divided into two types: medial pivot (MP) or non-MP. Knees with MP and non-MP patterns after implantation were compared in terms of postoperative flexion angle, pain, patient satisfaction, expectations, and activity using the new Knee Society Score 2011 at 1 year postoperatively. This study involved 55 patients (12 men, 43 women) with a mean age of 73.1 years and mean body mass index of 26.5 kg/m2. Preoperative kinematic measurements showed MP in 23 knees and non-MP in 32 knees. After implantation, navigation showed MP in 25 knees and non-MP in 30 knees. No significant differences were found between kinematic patterns preoperatively and after implantation. Postoperative flexion angle, pain, patient satisfaction, expectations, and activity using Knee Society Score 2011 showed no differences between MP and non-MP knees. Intraoperative knee kinematics as measured by navigation could not predict postoperative outcomes of TKA.


Moral asymmetries in judgments of agency withstand ludicrous causal deviance.
Americans have been shown to attribute greater intentionality to immoral than to amoral actions in cases of causal deviance, that is, cases where a goal is satisfied in a way that deviates from initially planned means (e.g., a gunman wants to hit a target and his hand slips, but the bullet ricochets off a rock into the target). However, past research has yet to assess whether this asymmetry persists in cases of extreme causal deviance. Here, we manipulated the level of mild to extreme causal deviance of an immoral versus amoral act. The asymmetry in attributions of intentionality was observed at all but the most extreme level of causal deviance, and, as we hypothesized, was mediated by attributions of blame/credit and judgments of action performance. These findings are discussed as they support a multiple-concepts interpretation of the asymmetry, wherein blame renders a naïve concept of intentional action (the outcome matches the intention) more salient than a composite concept (the outcome matches the intention and was brought about by planned means), and in terms of their implications for cross-cultural research on judgments of agency.


Development and evaluation of methods to detect nucleopolyhedroviruses in larvae of the Douglas-fir tussock moth, Orgyia pseudotsugata (McDunnough).
Various molecular methods are used to detect pathogenic microorganisms and viruses within their hosts, but these methods are rarely validated by direct comparison. Southern hybridization, enzyme-linked immunosorbent assay (ELISA), and a novel DNA extraction/PCR assay were used to detect Orgyia pseudotsugata multiple nucleopolyhedrovirus (OpMNPV) in Douglas-fir tussock moth larvae. PCR was more sensitive than Southern hybridization and ELISA at detecting semipurified virus. ELISA, however, was the most accurate method for detecting virus within larvae, given that Southern hybridization and PCR produced false-negative results (31% and 2.5%, respectively). ELISA may be preferable in some applications because virus infections can be quantified (r(2) = 0.995). These results may be applicable to both applied and academic research that seeks to accurately identify the incidence of viruses and microorganisms that regulate insect populations.


Impact of chronic unpredicted mild stress-induced depression on repaglinide fate via glucocorticoid signaling pathway.
Chronic unpredicted mild stress (CUMS)-induced depression could alter the pharmacokinetics of many drugs in rats, however, the underlying mechanism is not clear. In this work we studied the pharmacokinetics of repaglinide, and explored the role of glucocorticoid and adrenergic signaling pathway in regulating drug metabolizing enzymes (DMEs) in GK rats and BRL 3A cells. The plasma cortisol and epinephrine levels were increased, meanwhile the pharmacokinetics of repaglinide were altered significantly in depression model rats. Forty-nine genes in liver of model rats displayed significant difference comparing to control rats. The differentially expressed genes enriched in the drug metabolism and steroid hormone biosynthesis pathway significantly, and Nr1i3 matched 335 connectivity genes. CAR and Ugt1a1 protein expression were enhanced significantly in liver of model rats. The mRNA expression of Ugt1a1 and Nr1i2 were increased 2 and 4 times respectively with dexamethasone (DEX) and 8-Br-cAMP co-treatment in BRL 3A cells. The protein expression of PXR was up-regulated, too. However, RU486 reversed the up-regulated effect. The adrenergic receptor agonists had little impact on the DMEs in BRL 3A. Our data suggested that CUMS-induced depression might up-regulate DMEs expression via glucocorticoid signaling pathway, and accelerate the fate of the repaglinide in spontaneous diabetes rats.


Long-term durability of one-step adhesive-composite systems to enamel and dentin.
This study evaluated the long-term durability of three one-step adhesive-composite systems to ground enamel and dentin. Twenty-seven teeth were randomly divided into three groups of nine. The first group had its crowns sectioned to expose superficial dentin, which was then ground with 600 grit SiC paper. One of three one-step adhesives: a trial bonding agent, OBF-2; i Bond or Adper Prompt L-Pop was applied to the dentin of three teeth and built-up with the corresponding resin composite (Estelite sigma, Venus or Filtek Supreme). The second group of nine teeth had their enamel approximal surfaces ground with wet 600-grit SiC paper, then one of the three one-step adhesives was applied and built-up with resin composite. The bonded specimens were sliced into 0.7 mm-thick slabs. After 24 hours and one year of water storage at 37 degrees C, the slabs were sectioned into beams for the microtensile bond strength test. Failure modes were observed using optical and electron scanning microscopy. The third group of nine teeth had approximal wedge-shaped cavities prepared above the CEJ into dentin. Two-to-three grains of rhodamine B were added to each of the three adhesives prior to restoring the cavities with resin composite. After 24 hours storage, the teeth were sectioned and their interfaces examined with a laser scanning confocal microscope. The bond strengths of the three adhesive-composite systems to both enamel and dentin significantly lessened after one year of water storage, however, there was no significant difference between the materials.


Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease.
1,3-beta-D-glucan (BG) is a ubiquitous cell wall component of gut micro-organisms. We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease. To determine whether the serum BG concentrations correlate with intestinal inflammation. A prospective observational study was performed in a tertiary referral center, from 2016 to 2019, in which serum BG was determined in 115 patients with Crohn's disease (CD), 51 with ulcerative colitis (UC), and 82 controls using a photometric detection kit. Inflammatory activity was determined by ileocolonoscopy, histopathology, magnetic resonance enterography, and biomarkers, including fecal calprotectin (FC), C-reactive protein, and a panel of cytokines. The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve. In subgroup analysis, serial BG was used to assess the response to therapeutic interventions. The serum BG levels were higher in CD patients than in controls (P = 0.0001). The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients. The area under the curve (AUC) in receiver operating characteristic analysis to predict endoscopic activity was 0.694 [95% confidence interval (CI): 0.60-0.79; P = 0.001] in CD, and 0.662 (95%CI: 0.51-0.81; P = 0.066) in UC patients. The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860 (95%CI: 0.77-0.95; P < 0.001) in CD, and 0.786 (95%CI: 0.57-0.99; P = 0.015) in UC patients. The cut-off values of BG for both endoscopic and histologic activity were 60 µg/mL in CD, and 40 µg/mL in UC patients. Performance analysis showed that the results based on BG of 40 and 60 µg/mL were more specific for predicting endoscopic activity (71.8% and 87.2% for CD; and 87.5% and 87.5% for UC, respectively) than FC (53.3% and 66.7% for CD; and 20% and 80% for UC, respectively); and also histologic activity (60.5% and 76.3% for CD; and 90.0% and 95.0% for UC, respectively) than FC (41.7% and 50.0% for CD; and 25% and 50% for UC, respectively). Regarding the clinical, endoscopic, and histologic activities, the BG levels were reduced following therapeutic intervention in patients with CD (P < 0.0001) and UC (P = 0.003). Compared with endoscopic (AUC: 0.693; P = 0.002) and histologic (AUC: 0.868; P < 0.001) activity, no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography (AUC: 0.576; P = 0.192). Positive correlations were detected between BG and IL-17 in the CD (r: 0.737; P = 0.001) and the UC group (r: 0.574; P = 0.005), and between BG and interferon-gamma in the CD group (r: 0.597; P = 0.015). Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases, particularly in CD.


Quality of life in inflammatory bowel disease: background and definitions.
Defining and measuring quality of life is a relatively new dimension of health care for many clinicians. The traditional method of evaluating clinical status and response to treatment has been to look at disease-specific symptoms, global assessments (e.g., impressions of the good, better, or worse condition of a patient), days missed at school, and a variety of disease activity scores. These impressions and techniques may or may not reflect how patients are functioning day to day and how they feel about the illness. To address these issues, health-related quality of life questionnaires have been developed to measure the functional effect of an illness and its treatment on a patient, as perceived by the patient. There are four broad domains that are considered part of a health-related quality-of-life questionnaire: 1) physical and occupational function, 2) psychologic state, 3) social interaction, and 4) somatic sensation. In the case of children, the perception of parents or caretakers may be added to complete the picture. Significant social and psychiatric problems have been described in children with IBD, including absenteeism from school, depression, suicide, and major disruption of family patterns. To understand fully the impact of inflammatory bowel disease and its treatment on patient and family function requires one or more quality-of-life instruments that are sensitive to the full range of symptoms, growth and development, and response (including side effects) to many new therapies.


[Molecular diagnostic methods of respiratory infections. Has the scheme diagnosis changed?].
Lower respiratory tract infections remain one of the most common causes of mortality worldwide, which is why early diagnosis is crucial. Traditionally the microbiological diagnosis of these infections has been based on conventional methods including culture on artificial media for isolation of bacteria and fungi and cell cultures for virus and antibody or antigen detection using antigen-antibody reactions. The main drawback of the above mentioned methods is the time needed for an etiological diagnosis of the infection. The techniques based on molecular biology have drawn much attention in recent decades as tools for rapid diagnosis of infections. Some techniques are very expensive, especially those that can detect various microorganisms in the same reaction, therefore the question that arises is whether the cost of such testing is justified by the information obtained and by the clinical impact that its implementation will determine. In this article we make a review of the various techniques of molecular biology applied to the diagnosis of pneumonia and focus primarily on analysing the impact they may have on the management of patients with acute respiratory tract infections.


Chronic disease and chronic disease risk factors among First Nations, Inuit and Métis populations of northern Canada.
Aboriginal populations in northern Canada are experiencing rapid changes in their environments, which may negatively impact on health status. The purpose of our study was to compare chronic conditions and risk factors in northern Aboriginal populations, including First Nations (FN), Inuit and Métis populations, and northern non-Aboriginal populations. Data were from the Canadian Community Health Survey for the period from 2005 to 2008. Weighted multiple logistic regression models tested the association between ethnic groups and health outcomes. Model covariates were age, sex, territory of residence, education and income. Odds ratios (ORs) are reported and a bootstrap method calculated 95% confidence intervals (CIs) and p values. Odds of having at least one chronic condition was significantly lower for the Inuit (OR = 0.59; 95% CI: 0.43-0.81) than for non-Aboriginal population, but similar among FN, Métis and non-Aboriginal populations. Prevalence of many risk factors was significantly different for Inuit, FN and Métis populations. Aboriginal populations in Canada's north have heterogeneous health status. Continued chronic disease and risk factor surveillance will be important to monitor changes over time and to evaluate the impact of public health interventions.


Functional Relationship between Sucrose and a Cariogenic Biofilm Formation.
Sucrose is an important dietary factor in cariogenic biofilm formation and subsequent initiation of dental caries. This study investigated the functional relationships between sucrose concentration and Streptococcus mutans adherence and biofilm formation. Changes in morphological characteristics of the biofilms with increasing sucrose concentration were also evaluated. S. mutans biofilms were formed on saliva-coated hydroxyapatite discs in culture medium containing 0, 0.05, 0.1, 0.5, 1, 2, 5, 10, 20, or 40% (w/v) sucrose. The adherence (in 4-hour biofilms) and biofilm composition (in 46-hour biofilms) of the biofilms were analyzed using microbiological, biochemical, laser scanning confocal fluorescence microscopic, and scanning electron microscopic methods. To determine the relationships, 2nd order polynomial curve fitting was performed. In this study, the influence of sucrose on bacterial adhesion, biofilm composition (dry weight, bacterial counts, and water-insoluble extracellular polysaccharide (EPS) content), and acidogenicity followed a 2nd order polynomial curve with concentration dependence, and the maximum effective concentrations (MECs) of sucrose ranged from 0.45 to 2.4%. The bacterial and EPS bio-volume and thickness in the biofilms also gradually increased and then decreased as sucrose concentration increased. Furthermore, the size and shape of the micro-colonies of the biofilms depended on the sucrose concentration. Around the MECs, the micro-colonies were bigger and more homogeneous than those at 0 and 40%, and were surrounded by enough EPSs to support their structure. These results suggest that the relationship between sucrose concentration and cariogenic biofilm formation in the oral cavity could be described by a functional relationship.


Synthesis and Pharmacological Evaluation of Heterocyclic Carboxamides: Positive Allosteric Modulators of the M1 Muscarinic Acetylcholine Receptor with Weak Agonist Activity and Diverse Modulatory Profiles.
Targeting allosteric sites at M1 muscarinic acetylcholine receptors is a promising strategy for the treatment of Alzheimer's disease. Positive allosteric modulators not only may potentiate binding and/or signaling of the endogenous agonist acetylcholine (ACh) but also may possess direct agonist activity (thus referred to as PAM-agonists). Recent studies suggest that PAM-agonists with robust intrinsic efficacy are more likely to produce adverse effects in vivo. Herein we present the synthesis and pharmacological evaluation of a series of pyrrole-3-carboxamides with a diverse range of allosteric profiles. We proposed structural modifications at top, core, or pendant moieties of a prototypical molecule. Although generally there was a correlation between the degree of agonist activity and the modulatory potency of the PAMs, some derivatives displayed weak intrinsic efficacy yet maintained strong allosteric modulation. We also identified molecules with the ability to potentiate mainly the affinity or both affinity and efficacy of ACh.


[A case of gastric cancer accompanied by disseminated carcinomatosis of the bone marrow successfully controlled by S-1 and cisplatin combination therapy].
We report a case of gastric cancer accompanied by disseminated carcinomatosis of the bone marrow treated with S-1 and cisplatin( CDDP) combination chemotherapy. The patient was a 68-year-old woman who was detected as having disseminated intravascular coagulation( DIC) during an examination for gastric cancer and she was diagnosed as having disseminated carcinomatosis of the bone marrow by lumbar puncture. She was immediately treated with S-1 and CDDP combination chemotherapy( S-1, 80 mg/body orally administered[ po] on days 1-21 and CDDP, 60 mg/body intravenously [iv] administered on day 8) and her DIC improved on the fourth day. Subsequently, the patient was treated with 3 courses of combination chemotherapy and she survived for 184 days from the initiation of the treatment. Although disseminated carcinomatosis of the bone marrow is associated with a poor prognosis, we believe that the duration of survival of our patient was extended due to initiation of chemotherapy at an early stage.


Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways.
Methotrexate (MTX) is widely used as both an anticancer and anti-rheumatoid arthritis drug. Although MTX has been used to inhibit the growth of many cancer cells, it cannot effectively inhibit growth of triple-negative breast cancer cells (TNBC cells). Vitamin C is an antioxidant that can prevent oxidative stress. In addition, vitamin C has been applied as adjunct treatment for growth inhibition of cancer cells. Recent studies indicated that combined treatment with vitamin C and MTX may inhibit MCF-7 and MDA-MB-231 breast cancer cell growth through G2/M elongation. However, the mechanisms remain unknown. The aim of the present study was to determine whether combined treatment with low-dose vitamin C and MTX inhibits TNBC cell growth and to investigate the mechanisms of vitamin C/MTX-induced cytotoxicity. Neither low-dose vitamin C alone nor MTX alone inhibited TNBC cell growth. However, combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.


Tendons from non-diabetic humans and rats harbor a population of insulin-producing, pancreatic beta cell-like cells.
Diabetes mellitus is a risk factor for various types of tendon disorders. The mechanisms underlying diabetes associated tendinopathies remain unclear, but typically, systemic factors related to high blood glucose levels are thought to be causally involved. We hypothesize that tendon immanent cells might be directly involved in diabetic tendinopathy. We therefore analyzed human and rat tendons by immunohistochemistry, laser capture microdissection, and single cell PCR for pancreatic β-cell associated markers. Moreover, we examined the short term effects of a single injection of streptozotocin, a toxin for GLUT2 expressing cells, in rats on insulin expression of tendon cells, and on the biomechanical properties of Achilles tendons. Tendon cells, both in the perivascular area and in the dense collagenous tissue express insulin and Glut2 on both protein and mRNA levels. In addition, glucagon and PDX-1 are present in tendon cells. Intraperitoneal injection of streptozotocin caused a loss of insulin and insulin mRNA in rat Achilles tendons after only 5 days, accompanied by a 40% reduction of mechanical strength. In summary, a so far unrecognized, extrapancreatic, insulin-producing cell type, possibly playing a major role in the pathophysiology of diabetic tendinopathy is described. In view of these data, novel strategies in tendon repair may be considered. The potential of the described cells as a tool for treating diabetes needs to be addressed by further studies.


Cooling and control of a cavity optoelectromechanical system.
We implement a cavity optoelectromechanical system integrating electrical actuation capabilities of nanoelectromechanical devices with ultrasensitive mechanical transduction achieved via intracavity optomechanical coupling. Electrical gradient forces as large as 0.40 microN are realized, with simultaneous mechanical transduction sensitivity of 1.5x10{-18} m Hz{-1/2} representing a 3 orders of magnitude improvement over any nanoelectromechanical system to date. Optoelectromechanical feedback cooling is demonstrated, exhibiting strong squashing of the in-loop transduction signal. Out-of-loop transduction provides accurate temperature calibration even in the critical paradigm where measurement backaction induces optomechanical correlations.


Radiation-induced autophagy contributes to cell death and induces apoptosis partly in malignant glioma cells.
Radiation-induced autophagy has been shown to play two different roles, in malignant glioma (MG) cells, cytocidal or cytoprotective. However, neither the role of radiation-induced autophagy for cell death nor the existence of autophagy-induced apoptosis, a well-known cell-death pathway after irradiation, has been verified yet. We observed both temporal and dose-dependent response patterns of autophagy and apoptosis to radiation in MG cell lines. Additionally, we investigated the role of autophagy in apoptosis through knockdown of autophagy-related proteins. Autophagic activity measured by staining of acidic vesicle organelles and Western blotting of LC-3 protein increased in proportion to radiation dose from day 1 to 5 after irradiation. Apoptosis measured by annexin-V staining and Western blotting of cleaved poly(ADP-ribose) polymerase demonstrated relatively late appearance 3 days after irradiation that increased for up to 7 days. Blocking of pan-caspase (Z-VAD-FMK) did not affect apoptosis after irradiation, but silencing of Atg5 effectively reduced radiation-induced autophagy, which decreased apoptosis significantly. Inhibition of autophagy in Atg5 knockdown cells was shown to be beneficial for cell survival. Stable transfection of GFP-LC3 cells was observed after irradiation. Annexin-V was localized in cells bearing GFP-LC3 punctuated spots, indicating autophagy in immunofluorescence. Some of these punctuated GFP-LC3 bearing cells formed conglomerated spots and died in final phase. These findings suggest that autophagy appears earlier than apoptosis after irradiation and that a portion of the apoptotic population that appears later is autophagy-dependent. Thus, autophagy is a pathway to cell death after irradiation of MG cells.


Establishing a master's degree programme in bioinformatics: challenges and opportunities.
The development of the Bioinformatics MS degree program at the University of Illinois, the challenges and opportunities associated with such a process, and the current structure of the program is described. This program has departed from earlier University practice in significant ways. Despite the existence of several interdisciplinary programs at the University, a few of which grant degrees, this is the first interdisciplinary program that grants degrees and formally recognises departmental specialisation areas. The program, which is not owned by any particular department but by the Graduate College itself, is operated in a franchise-like fashion via several departmental concentrations. With four different colleges and many more departments involved in establishing and operating the program, the logistics of the operation are of considerable complexity but result in significant interactions across the entire campus.


Age-stage, two-sex life table of Parapoynx crisonalis (Lepidoptera: Pyralidae) at different temperatures.
Parapoynx crisonalis is an important pest of many aquatic vegetables including water chestnuts. Understanding the relationship between temperature variations and the population growth rates of P. crisonalis is essential to predicting its population dynamics in water chestnuts ponds. These relationships were examined in this study based on the age-stage, two-sex life table of P. crisonalis developed in the laboratory at 21, 24, 27, 30, 33 and 36°C. The results showed that the values of Sxj (age-stage-specific survival rate), fxj (age-stage-specific fecundity), lx (age specific survival rate) and mx (age-specific fecundity) increased as the temperature rose from 21 to 27°C, then decreased from 30 to 36°C. Temperature also had a significant effect on the net reproductive rate (R0), gross reproductive rate (GRR), intrinsic rate of increase (r) and finite rate of increase (λ). The value of these parameters were at low levels at 21, 33, and 36°C. Further, the r value decreased as the temperature rose from 24 to 30°C, while the GRR reached its highest level at 27°C. The results indicated that optimal growth and development of P. crisonalis occurred at temperatures between 24°C to 30°C when compared to the lowest temperature (21°C) and higher temperatures of 33°C and 36°C.


Decoy Receptor 3 Promotes Preosteoclast Cell Death via Reactive Oxygen Species-Induced Fas Ligand Expression and the IL-1α/IL-1 Receptor Antagonist Pathway.
Interleukin-1α (IL-1α) is a potent cytokine that plays a role in inflammatory arthritis and bone loss. Decoy receptor 3 (DCR3) is an immune modulator of monocytes and macrophages. The aim of this study was to investigate the mechanism of DCR3 in IL-1α-induced osteoclastogenesis. We treated murine macrophages with DCR3 during receptor activator of nuclear factor kappa Β ligand- (RANKL-) plus IL-1α-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed using a pit formation assay. The mechanisms of inhibition were studied by biochemical analyses, including RT-PCR, immunofluorescent staining, flow cytometry, an apoptosis assay, immunoblotting, and ELISA. DCR3 suppresses IL-1α-induced osteoclastogenesis in both primary murine bone marrow-derived macrophages (BMM) and RAW264.7 cells as it inhibits bone resorption. DCR3 induces RANKL-treated osteoclast precursor cells to express IL-1α, secretory IL-1ra (sIL-1ra), intracellular IL-1ra (icIL-1ra), reactive oxygen species (ROS), and Fas ligand and to activate IL-1α-induced interleukin-1 receptor-associated kinase 4 (IRAK4). The suppression of DCR3 during RANKL- or IL-1α-induced osteoclastogenesis may be due to the abundant secretion of IL-1ra, accumulation of ROS, and expression of Fas ligand in apoptotic osteoclast precursor cells. We concluded that there is an inhibitory effect of DCR3 on osteoclastogenesis via ROS accumulation and ROS-induced Fas ligand, IL-1α, and IL-1ra expression. Our results suggested that the upregulation of DCR3 in preosteoclasts might be a therapeutic target in inflammatory IL-1α-induced bone resorption.


Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines.
Breast cancer progression is composed of multiple steps that are influenced by tumor cell adaptations to survive under acidic conditions in the tumor microenvironment. Regulation of this cell survival behavior is a promising strategy to avoid cancer development. Melatonin is a natural hormone produced and secreted by the pineal gland capable of modulating different biological pathways in cancer. Although the anti-cancer effects of melatonin are currently widespread, its role in the acid tumor microenvironment remains poorly understood. The aim of the present study was to investigate the effect of low pH (6.7) on human breast cancer cell lines MCF-7 and MDA-MB-231, and the effectiveness of melatonin in acute acidosis survival mechanisms. Cell viability was measured by a MTT assay and the protein expression of glucose transporter (GLUT)-1, Ki-67 and caspase-3 was evaluated by immunocytochemical (ICC) analysis following low pH media and melatonin treatment. In both cell lines the viability was decreased after melatonin treatment (1 mM) under acidosis conditions for 24 h. ICC analysis showed a significant increase in GLUT-1 and Ki-67 expression at pH 6.7, and a decrease after treatment with melatonin for 12 and 24 h. The low pH media decreased the expression of caspase-3, which was increased after melatonin treatment for 12 and 24 h. Overall, the results of the present study revealed melatonin treatment increases apoptosis, as indicated by changes in caspase-3, and decreases proliferation, indicated by changes to Ki-67, and GLUT-1 protein expression under acute acidosis conditions in breast cancer cell lines.


[An economic evaluation of low dose recombinant human tissue-type plasminogen activator for the treatment of acute pulmonary thromboembolism].
To compare and evaluate the cost and effectiveness between recombinant human tissue-type plasminogen activator (rt-PA) 50 mg and 100 mg regimen for the treatment acute pulmonary thromboembolism (PTE). Based on a randomized clinical trial data, 118 cases were enrolled, 65 cases in group 50 mg and 53 cases in group 100 mg, which showed the similar efficacy and safety of rt-PA 50 mg and 100 mg. Progressive improvement in pulmonary artery obstructions was found to be similarly significant in both treatment groups, but there was no significant differences between the two groups (89.1% vs 89.6%, chi(2) = 0.007, P = 0.936). The rates of adverse events in two groups were same as well (17% vs 32%, chi(2) = 3.704, P = 0.054). We compared the cost directly and the cost-effective rate of the two groups. Based the cost saving of individual patient, prevalence rate of acute PTE, and co-pay rate of reimbursement, we calculated the cost saving of societal and payer's perspective. The cost of group 50 mg is 6352 RMB/person, and the cost of group 100 mg is 12,704 RMB/person. The cost-effect rates of the two groups were 7129 and 14,179 separately. With the same effect, each patient in 50 mg group can save 7050 RMB. If the PTE patients in China were treated with rt-PA 50 mg instead of 100 mg, the society cost saving would be 443,604,624 RMB. rt-PA 50 mg/2 h regimen, compared with 100 mg/2 h, can not only provide similar efficacy and safety, but also show a good health economic saving.


Self-regressing S100-negative CD1a-positive cutaneous histiocytosis.
In the skin, the antigen-presenting cells are mainly represented by Langerhans cells, indeterminate cells, and interstitial dendritic cells, which show distinctive immunophenotype and/or ultrastructure. We report a case of a cutaneous-limited self-regressing histiocytosis with a peculiar immunohistochemical profile (CD1a-positive and S100 protein-negative) that is not observed in any of the known cutaneous antigen-presenting cell or nowadays recognized neoplasm. This lesion is probably related to indeterminate dendritic cell tumors, but very few cases with such immunoprofile have been reported up-to-date, and their exact nosologic position and outcome remain to be clarified.


University-affiliated venture capital funds.
This paper briefly reviews university/industry licensing and research collaborations and focuses on three university-affiliated venture capital funds, which represent the most direct participation by academic institutions in creating new ventures based on technologies invented by their faculty members. The paper provides an early perspective on these funds as mechanisms for bringing new biomedical technologies into use. Although the new models have not existed long enough to fully evaluate their effectiveness, the early evidence is sufficient to suggest helpful guidelines for development of more efficient initiatives in the future.


High-Resolution Tissue Mass Spectrometry Imaging Reveals a Refined Functional Anatomy of the Human Adult Adrenal Gland.
In the adrenal gland, neuroendocrine cells that synthesize catecholamines and epithelial cells that produce steroid hormones are united beneath a common organ capsule to function as a single stress-responsive organ. The functional anatomy of the steroid hormone-producing adrenal cortex and the catecholamine-producing medulla is ill defined at the level of small molecules. Here, we report a comprehensive high-resolution mass spectrometry imaging (MSI) map of the normal human adrenal gland. A large variety of biomolecules was accessible by matrix-assisted laser desorption/ionization-Fourier transform-ion cyclotron resonance MSI, including nucleoside phosphates indicative of oxidative phosphorylation, sterol and steroid metabolites, intermediates of glycolysis and the tricarboxylic acid cycle, lipids, and fatty acids. Statistical clustering analyses yielded a molecularly defined adrenal anatomy of 10 distinct molecular zones including a highly structured corticomedullary interface. By incorporating pathway information, activities of carbohydrate, amino acid, and lipid metabolism as well as endocrine bioactivity were revealed to be highly spatially organized, which could be visualized as different molecularly defined zones. Together, these findings provide a molecular definition of human adult adrenal gland structure beyond classical histological anatomy.


Choice of dental care among 16--18 year olds in Oslo.
One of the objectives of organized school dental service is to create ability and willingness among young adults to maintain a preventive oral health care, e.g. regular dental visits. In order to investigate the decisions about and plans for dental care among school dental service leavers a questionnaire was sent to a probability sample of 258 young adults who had finished ninth grade eight months earlier. The participation rate of the Youth Dental Program (YDP) was approximately 90%. The drop-outs were made up of at least two rather distinct groups. One of them was dominated by subjects with a high social background and they chose to a great extent care in private practice. The other group was dominated by young men with a low social background. They finished school early and expressed pessimistic expectations to the life-time of their own teeth.


[A discussion on influence of philosophical idea of Guan Zi on TCM].
Guan Zi has substantial content and deep idea, being paid great attention among the various ancient schools of thought. After discussing the influence of its philosophical idea on TCM, it can be concluded that Guan Zi raised Yin Yan concept to a natural law earlier after Lao Zi first philosophized it. Meanwhile discussed the relationship between Yin and Yang systematically such as respecting Yang, Yang can control Yin, and relativity of Yin and Yang. It first setup Jing -Qi Theory, discussing materiality of the Nature and life from the sense of ontology. But it confused Jing Shen and Jing Qi, and could not weep the primitive color of Xing-Shen Monism. It emphasized on self-cultivation and embodied Xu (voidness), Yi (unity), Jing (tranquility) and Yin (cause) on preserving health.


A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.
BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.


Anticoagulation for the Pregnant Patient with a Mechanical Heart Valve, No Perfect Therapy: Review of Guidelines for Anticoagulation in the Pregnant Patient.
Heart valve replacement with a mechanical valve requires lifelong anticoagulation. Guidelines currently recommend using a vitamin K antagonist (VKA) such as warfarin. Given the teratogenic effects of VKAs, it is often favorable to switch to heparin-derived therapies in pregnant patients since they do not cross the placenta. However, these therapies are known to be less effective anticoagulants subjecting the pregnant patient to a higher chance of a thrombotic event. Guidelines currently recommend pregnant women requiring more than 5 mg a day of warfarin be switched to alternative therapy during the first trimester. This case report highlights a patient who was switched to alternative therapy during her first pregnancy and suffered a devastating cerebrovascular accident (CVA). Further complicating her situation was during a subsequent pregnancy; this patient continued warfarin use during the first trimester and experienced multiple transient ischemic attacks (TIAs). This case highlights the increased risk of thrombotic events in pregnant patients with mechanical valves. It also highlights the difficulty of providing appropriate anticoagulation for the pregnant patient who has experienced thrombotic events on multiple anticoagulants.


In vivo 31P nuclear magnetic resonance measurements in canine heart using a catheter-coil.
We have developed a new method of obtaining high resolution 31P nuclear magnetic resonance spectra from canine heart without the need for major surgery. This is done by passing an elliptical nuclear magnetic resonance receiver coil through a peripheral blood vessel into the right or left ventricle. This technique enables spectra to be obtained from a defined region of myocardium in less than 7 minutes (for the right ventricle) with a signal:noise ratio of greater than 9:1. With this catheter-coil, useful cardiac metabolic information will be obtainable, not only from specified regions of the heart, but also from various layers of myocardium.


Extreme electric fields power catalysis in the active site of ketosteroid isomerase.
Enzymes use protein architecture to impose specific electrostatic fields onto their bound substrates, but the magnitude and catalytic effect of these electric fields have proven difficult to quantify with standard experimental approaches. Using vibrational Stark effect spectroscopy, we found that the active site of the enzyme ketosteroid isomerase (KSI) exerts an extremely large electric field onto the C=O chemical bond that undergoes a charge rearrangement in KSI's rate-determining step. Moreover, we found that the magnitude of the electric field exerted by the active site strongly correlates with the enzyme's catalytic rate enhancement, enabling us to quantify the fraction of the catalytic effect that is electrostatic in origin. The measurements described here may help explain the role of electrostatics in many other enzymes and biomolecular systems.


[Univentricular heart; angiocardiographic study].
Authors present angiocardiographic study of 19 patients with univentricular heart. It was realized during the neonatal period in 13 cases and between the six first six months in the rest. To determine the existence of an only ventricle contrast was injected in the right and left atrium and the ventricle through the right and left atrioventricular valve. The bulbo-ventricular foramen was orientated in all cases from back-front wards. Those of left ventricle type had a right anterior, anterior-superior or left-anterior rudimentary chamber. Depending on its' morphology they were classified in three types: left, right or indeterminate. In these series fourteen patients had left ventricle morphology. All cases had a rudimentary chamber: 10 with transposition great vessel and four with normal related great vessels. Six presented normal situs (five with levocardia , and eight ambiguous situs (six with asplenia, four with dextrocardia). In nine atrio ventricular valves were anomalous. In the indeterminate type, two had a normal situs, two with polysplenia and two asplenia. Cardiac apex was oriented to the right in two (one asplenia). The two patients with polysplenia and one with normal situs and single atrium had a common ventricular valve. Four had an anterior aorta and three pulmonary obstruction.


Endemic palm species shed light on habitat shifts and the assembly of the Cerrado and Restinga floras.
Species expansions into new habitats are often associated with physiological adaptations, for instance when rain forest lineages colonize dry habitats. Although such shifts have been documented for the Brazilian savanna (Cerrado), little is known about the biogeographic origin of species occupying an extreme South American habitat type, the coastal dunes (Restinga). We examined the formation of this poorly known, endangered habitat by reconstructing the evolutionary history of two endemic species. Due to the proposed recency and uniqueness of this habitat, we hypothesized that Restinga species of the palm genus Allagoptera to be recently evolved and to present derived morphological characters. To detect habit shifts in absolute time, we used one plastid and nine nuclear genes to reconstruct the phylogenetic and biogeographic history of Allagoptera. We used light microscopy and stable isotope analysis to explore whether morphological adaptations occurred concomitantly with habitat shifts. Phylogenetic relationships were well supported and we found ancestral lineages of Allagoptera to be widely distributed throughout habitats that are currently occupied by extant species. Over the last ca. 7Ma Allagoptera has shifted its preference to increasingly dry habitats. Coincident with the colonization of the Cerrado and Restinga, morphological adaptations also evolved, including subterranean stems that are fire-resistant and long underground stem and root systems that facilitate water access. We did not find differences in metabolic pathway or modifications to pollen morphology when compared to other palm lineages. Assuming that the evolutionary history of Allagoptera is indicative of the habitat in which it occurs, our results infer a recent origin for Cerrado species. Although little is known about the formation of the Restinga habitat, our results also suggest a longer history than currently proposed; with an origin of Restinga habitats dating back to the Late Pliocene.


Patterns and economic effects of drug overdose mortality in Texas: 1980-1986.
Drug overdose mortality and its economic consequences are explored for ten different drug categories in this article. Data on drug overdose mortality in Texas for the years 1980-1986 are examined and a cost of mortality analysis is presented using the human capital methodology. In addition, mortality rates per 100,000 population are presented for each drug category. The results indicate that the cost of drug overdose mortality has more than doubled over the six-year period. The greatest growth in mortality cost has been for narcotics and cocaine, with commonly prescribed psychoactive drugs remaining fairly constant. The results suggest that men are at far greater risk of drug overdose than women with respect to illicit drugs. Women, however, appear to be at greater risk for overdose from commonly prescribed drugs.


First paralytic shellfish poison (PSP) infestation of bivalves due to toxic dinoflagellate Alexandrium tamiyavanichii, in the southeast coasts of the Seto Inland Sea, Japan.
The mussel Mytilus edulis and the cultured ark shell Anadara broughtonii in the southeast coasts of the Seto Inland Sea were contaminated with paralytic shellfish poison (PSP) following the appearance of the dinoflagellate Alexandrium tamiyavanichii in early December 1999. A. tamiyavanichii plankton collected around the Straits of Naruto on December 3, 1999 showed PSP toxicity, of which 83 mol% was accounted for by GTX2, GTX3 and GTX4. Its specific toxicity was 112.5 fmol/cell, and one MU was equivalent to 7,200 cells. Toxicity values at the beginning of toxification were 4.7 MU/g for the ark shell and 7.3 MU/g for the mussel. In the former, the value remained at almost 4 MU/g, resulting in prohibition of marketing for about two months. In the latter, it sharply decreased to less than 4 MU/g. These bivalves collected during the toxification period were dissected into five tissues, mantle, adductor muscle, hepatopancreas, gills and "others", and submitted to high-performance liquid chromatography (HPLC). The cultured ark shell accumulated GTX2, GTX3 and STX as major components and GTX1, GTX4, GTX5, neoSTX, dcSTX and PX1-3 (C1-C3) as minor ones. The amount of GTX3 decreased with time, while STX tended to increase. At the early stage of PSP toxification, toxins were accumulated in the gills and "others", most of which were quickly detoxified. On the other hand, PSP of the toxified mussel consisted of GTX4 as a main component, and GTX1, GTX2, GTX3, GTX5, STX and PX1-2 (C1-C2) as minor ones. Its toxin composition pattern was similar to that of the ingested causative plankton. Its total toxin decreased soon after disappearance of the dinoflagellate. During the decrease of toxicity, PSP tended to be retained in the hepatopancreas, resulting in accumulation of 50 mol% of total toxin.