Three‑time point view of mild brain injuries' structural alteration and their association with cognitive domains.
Mild traumatic brain injury (mTBI) accounts for 70‑80% of total neurotrauma, majority among them manifest with cognitive deficits. Till date there are few/or no 3‑time‑point longitudinal studies that have evidenced brain volume changes. The current study has investigated volume changes at 3‑time‑points and their association with cognitive sequel. Twenty‑one mTBI patients with normal imaging and 15 GCS were recruited. Initially these patients were evaluated with magnetic resonance imaging (MRI) scan ≤36hours and neuropsychological test (NPT) during 2‑3weeks after‑injury. All the patients were available for follow‑up for repeat MRI and NPT on 3‑4 and 6‑7months. The imaging and test scores were analyzed using repeated measures of analysis (P<0.05). The brain volumes were correlated with respective test‑scores using partial‑correlation. Left frontal lobe (P<0.029) and thalamus (P=0.049) showed significant increase in mean volume overtime, whereas corpus callosum (mid‑anterior [P=0.011] and central [P=0.04]) and left cerebellum (P=0.043) showed significant decrease in mean volume overtime. Clinically cognitive scores improved with time. Eventual improvements in attention and memory scores were positively associated with increase in cingulate gyrus volume. The 3‑time‑point longitudinal study illustrates brain areas that changes with time and their association with improving cognitive scores. The study provides hint about the pattern of natural recovery.


Black/white differential use of health services by young children in a rural Mississippi community.
Use of health services in rural communities has not been well studied. We explored how black and white children used health services in a rural Mississippi community. Data were prospectively collected for 396 children attending a private practice to determine if race was associated with the use of health services in this community. White children made more sick contacts than black children (P < 0.001). Black children (36%) were more likely to be treated in the emergency room than white children (24%; P = 0.013). There was no black-white difference in the hospitalization rates, although white children were more likely to undergo ear-nose-throat (ENT) surgery for pressure equalizing tube (PET) placement, and/or tonsillectomy and adenoidectomy (T and A; P < 0.001). Even after controlling for various confounders, the frequency of all physician sick contacts was twice as high for white children than for black children (RR = 2.17; 95% C.I. = 1.32-3.58). Overall, black children used disproportionately fewer health services than their white counterparts, but used significantly higher emergency room services. Private insurance coverage was the single most significant variable that accounted for the black-white differential use of the emergency room.


Use of fan beam dual energy x-ray absorptiometry to measure body composition of piglets.
A piglet model was used to determine whether the fan beam dual energy X-ray absorptiometry technique (DXA) could be adapted for the measurement of body composition of small subjects. Commercial domestic swine piglets (n = 14) with weights between 1.95 and 21.1 kg had duplicate fan beam-DXA scans followed by chemical analysis of body composition. Each scan required 2-3 min to complete. DXA-measured total body weight was validated against scale weights of the piglets (with and without blanket and other covering), DXA bone mineral content validated against carcass ash and calcium, and DXA lean and fat mass validated against chemical lean and fat contents. Measurements from duplicate DXA scans were highly reproducible with adjusted r(2) values from 0.992 to 1.000. Each DXA measurement was highly predictive of the scale weight or specific chemical body composition with adjusted r(2) values from 0.974 to 0.999. The intraclass reliability coefficient among measurements from individual scans with scale weight or the weight of individual chemical components was extremely high at > or =0.99 for all comparisons. The SD of residuals for DXA prediction of scale weights (with and without covering) were 168 and 157 g, respectively, and were 27, 8.8, 122 and 72 g for the prediction of carcass ash, calcium, lean and fat tissue content, respectively. We conclude that rapid scan acquisition, accurate and precise prediction of scale weight and components of body composition would support the use of fan beam-DXA for body composition studies in growing humans or animals.


Comparison of salivary gland MRI and ultrasonography findings among patients with Sjögren's syndrome over a wide age range.
This retrospective study compared MRI and US findings among patients with SS over a wide age range. Ninety patients with SS aged 8-84 years who had undergone both MRI and US examinations were divided into four groups according to age, as follows: <18 years (juvenile SS, JSS), 9 patients; 18-39 years, 12 patients; 40-69 years, 53 patients; >69 years, 16 patients. Imaging findings of parotid glands (PGs) and submandibular glands (SMGs) were compared among the four groups. Furthermore, the relationships within and between imaging findings and various clinical findings were examined. On MRI, patients with JSS commonly exhibited multiple high-intensity spots in the PGs on MR sialography and fat-suppressed T2-weighted imaging. With increasing SS group age, the frequencies and numbers of the high-intensity spots were lower. Fat areas on MRI and hyperechoic bands on US were rarely observed in the PGs and SMGs of patients with JSS, whereas they were more common in patients with adult SS. In addition, the presence of hyperechoic bands on US, the presence of fat areas on MRI, and decreased salivary flow were associated with one another. Salivary gland imaging findings in patients with JSS were characterized by punctate sialectasis, whereas those findings in patients with adult SS were characterized by fatty degeneration. Distinct findings in patients with JSS and adult SS are likely to reflect differences in glandular lesion stage. MRI and US are presumably useful for evaluation of glandular lesion severity during follow-up.


A custom mandibular distraction device for the rat.
In the last several years, the rat model has been used as a reliable means of studying distraction osteogenesis (DO). This model has several benefits, including lower cost, the availability of molecular reagents for the rat, and the ability to perform a large number of operations in a short time. We have recently developed an external device that is custom-made for the rat mandible and secured at the mandibular ramus. The device consists of a Leone (Florence, Italy) jackscrew distraction assembly (0.2 mm per one-quarter turn), 2 Luhr L-shaped 0.8-mm five-hole microplates, and four 0.8-mm x 3-mm microscrews (Stryker-Leibinger Corp., Kalamazoo, MI) for fixation. Additionally, there is a methylmethacrylate block that is placed on the lingual surface of the angle of the mandible to support the posterior screws. Sterile surgical technique was used, and the same two surgeons performed all operations. To date, we have operated on 153 Sprague-Dawley rats. The procedure has been well tolerated by the animals. We had 17 postoperative deaths (11% mortality), largely as a result of anesthetic complications. There were no wound infections or dehiscence. A mandible fracture was noted in 6 rats (4%), which occurred at the time of device placement. There were no device dislodgments. Postmortem examination showed the device to be well positioned in all rats, with good callous formation at the distraction site. The rats surpassed their preoperative weight after an average of 9.2 days. These results compare favorably with those of other models currently in use. We have developed a device that is currently being used in the study of DO in the rat mandible. Our device is small in size, does not require wide undermining for its placement, and has had a low incidence of device dislodgment or infection. This model has shown great reproducibility and thus should be effective in its application for the histologic and biochemical investigation of DO in the rat.


Tunable Ambipolar Polarization-Sensitive Photodetectors Based on High-Anisotropy ReSe2 Nanosheets.
Atomically thin 2D-layered transition-metal dichalcogenides have been studied extensively in recent years because of their intriguing physical properties and promising applications in nanoelectronic devices. Among them, ReSe2 is an emerging material that exhibits a stable distorted 1T phase and strong in-plane anisotropy due to its reduced crystal symmetry. Here, the anisotropic nature of ReSe2 is revealed by Raman spectroscopy under linearly polarized excitations in which different vibration modes exhibit pronounced periodic variations in intensity. Utilizing high-quality ReSe2 nanosheets, top-gate ReSe2 field-effect transistors were built that show an excellent on/off current ratio exceeding 10(7) and a well-developed current saturation in the current-voltage characteristics at room temperature. Importantly, the successful synthesis of ReSe2 directly onto hexagonal boron nitride substrates has effectively improved the electron motility over 500 times and the hole mobility over 100 times at low temperatures. Strikingly, corroborating with our density-functional calculations, the ReSe2-based photodetectors exhibit a polarization-sensitive photoresponsivity due to the intrinsic linear dichroism originated from high in-plane optical anisotropy. With a back-gate voltage, the linear dichroism photodetection can be unambiguously tuned both in the electron and hole regime. The appealing physical properties demonstrated in this study clearly identify ReSe2 as a highly anisotropic 2D material for exotic electronic and optoelectronic applications.


Successful tracheal weaning.
In 1994, neuroscience nurses and neurosurgeons at St. Boniface General Hospital and the Health Sciences Centre in Winnipeg completed a study on tracheostomy weaning. This collaborative effort was initiated in response to a perceived clinical need--weaning difficulties in our neurological and neurosurgical patients--and was the first step along the road to implementing a standardized weaning procedure.


Prognostic role of inflammatory biomarkers in metastatic breast cancer.
The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (β2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). Serum CRP, ferritin and β2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.


Evaluating clinician-led quality improvement initiatives: A system-wide embedded research partnership at Stanford Medicine.
Many healthcare delivery systems have developed clinician-led quality improvement (QI) initiatives but fewer have also developed in-house evaluation units. Engagement between the two entities creates unique opportunities. Stanford Medicine funded a collaboration between their Improvement Capability Development Program (ICDP), which coordinates and incentivizes clinician-led QI efforts, and the Evaluation Sciences Unit (ESU), a multidisciplinary group of embedded researchers with expertise in implementation and evaluation sciences. To describe the ICDP-ESU partnership and report key learnings from the first 2 y of operation September 2019 to August 2021. Department-level physician and operational QI leaders were offered an ESU consultation to workshop design, methods, and overall scope of their annual QI projects. A steering committee of high-level stakeholders from operational, clinical, and research perspectives subsequently selected three projects for in-depth partnered evaluation with the ESU based on evaluability, importance to the health system, and broader relevance. Selected project teams met regularly with the ESU to develop mixed methods evaluations informed by relevant implementation science frameworks, while aligning the evaluation approach with the clinical teams' QI goals. Sixty and 62 ICDP projects were initiated during the 2 cycles, respectively, across 18 departments, of which ESU consulted with 15 (83%). Within each annual cycle, evaluators made actionable, summative findings rapidly available to partners to inform ongoing improvement. Other reported benefits of the partnership included rapid adaptation to COVID-19 needs, expanded clinician evaluation skills, external knowledge dissemination through scholarship, and health system-wide knowledge exchange. Ongoing considerations for improving the collaboration included the need for multi-year support to enable nimble response to dynamic health system needs and timely data access. Presence of embedded evaluation partners in the enterprise-wide QI program supported identification of analogous endeavors (eg, telemedicine adoption) and cross-cutting lessons across QI efforts, clinician capacity building, and knowledge dissemination through scholarship.


An economic evaluation of asthma action plans for children with asthma.
The costs and effectiveness of asthma action plans for children were evaluated in a cross-sectional economic analysis. Direct health care and indirect costs, nights with symptoms, and asthma attacks were measured in 879 Ontario children with asthma. From a societal perspective, the total annual costs of the asthma action plan and the control groups were CDN$6,948 and CDN$6,140 per patient, respectively. Health outcomes were similar. The difference in cost was attributable to greater medication and health services use in the intervention group. Prospective randomized trials are necessary to measure potential improvements in control of asthma using asthma action plans.


Plasma cyclic nucleotide levels in acute leukemia patients.
To verify the clinical usefulness of extracellular cyclic nucleotide determination as a tumor marker, plasma cyclic AMP (cAMP) and cyclic GMP (cGMP) levels were measured in 70 normal subjects and 173 acute leukemia patients studied in different stages of their disease. Mean plasma cAMP levels were similar in leukemic and normal subjects, although in 48 patients in the active stage of the disease, first diagnosis, or relapse, the cAMP values were below the normal range, and most of these patients failed to respond to chemotherapy. Plasma cGMP levels were markedly elevated in untreated patients, normalized in all patients who attained complete remission, and increased promptly to pretreatment values in patients who relapsed, suggesting that their determination may be useful to monitor the patients' response to treatment.


'Gastro' of Mirpur Khas (Sindh) is resolved.
Diarrhoeal disease is a common cause of major public health concern in many parts of the world including Pakistan. Eighteen stool samples were received from Civil Hospital Mirpur Khas (Sindh). All the specimens were processed for culture and antimicrobial susceptibility according to Clinical Laboratory Standards Institute (CLSI) guidelines. Eight out of eighteen (44.4%) samples were positive for Vibrio cholerae. The isolates were gram negative rods, showed darting motility and were Oxidase positive. Contact with distilled water immobilized all these strains (Mdw). API 20NE was used for the biochemical identification and serological confirmation was done with 'difco' antisera. Kirby-Bauer disc diffusion method was performed for their respective susceptibility to various antibiotics. All these isolates were confirmed to be Vibrio cholerae O1 Biotype El Tor Serotype Ogawa. The isolates were generally sensitive to majority of the antibiotics but resistant to nalidixic acid except one strain. Six out of eight isolates were resistant to co-trimoxazole. Cholera must be suspected in outbreaks of such kind of 'gastro'.


Mechanism of Photoredox-Initiated C-C and C-N Bond Formation by Arylation of IPrAu(I)-CF3 and IPrAu(I)-Succinimide.
Herein, we report on the photoredox-initiated gold-mediated C(sp2)-CF3 and C(sp2)-N coupling reactions. By adopting gold as a platform for probing metallaphotoredox catalysis, we demonstrate that cationic gold(III) complexes are the key intermediates of the C-C and C-N coupling reactions. The high-valent gold(III) intermediates are accessed by virtue of photoredox catalysis through a radical chain process. In addition, the bond-forming step of the coupling reactions is the reductive elimination from cationic gold(III) intermediates, which is supported by isolation and crystallographic characterization of key Au(III) intermediates.


Micron and submicron patterning of dicyanopyrazine-linked porphyrin molecules using micro-contact printing and Langmuir-Blodgett assembly.
We describe a method to conveniently fabricate micron- and submicron-sized patterns of well-ordered and densely-packed dicyanopyrazine-linked porphyrin (4-TDCPP) molecules by using micro-contact printing (micro-CP) in conjunction with Langmuir-Blodgett (LB) deposition. SEM and AFM images reveal that the sizes and shapes of the 4-TDCPP patterns are well-matched with the geometric features of the polydimethylsiloxane (PDMS) stamps used for micro-CP. Fluorescence images show strong, red emission from the 4-TDCPP patterns. However, the thicknesses of the 4-TDCPP patterns transferred onto a silicon substrate by micro-CP are not the same, even though the same amount of 4-TDCPP layers are deposited on the surface of PDMS stamps in the LB process. The thicknesses of the 10 microm line, 2 microm dot and 300 nm line patterns of 10-layered 4-TDCPP molecules are 34.6, 26.7 and 5.9 nm, respectively. These differences may be due to variations in adhesion forces between the silicon substrate and 4-TDCPP on PDMS stamps having different size patterns. Larger patterns have greater contact areas compared to smaller patterns. This phenomenon can cause stronger adhesion forces, resulting in greater pattern thickness.


Acquired ornithine transcarbamylase deficiency in pediatric and adolescent patients with fibrolamellar hepatocellular carcinoma.
Ornithine transcarbamylase deficiency (OTCD) disrupts the metabolic pathway responsible for converting nitrogenous waste to urea, allowing for excretion. When impaired, ammonia levels accumulate in the blood resulting in severe, sometimes life-threatening toxicities. Abnormalities of the urea cycle are often inherited, though there are some rarer acquired forms. We describe two cases of acquired OTCD in pediatric patients with fibrolamellar hepatocellular carcinoma (FL-HCC). We detail its presentation and management, explore potential underlying pathophysiology, and propose a practice change to optimize care of FL-HCC patients.


Mechanisms of H1o accumulation in mouse neuroblastoma cells differ with different treatments.
The accumulation of histone H1o in mouse NIE-115 neuroblastoma cells was measured during the course of three treatments that block cell division. Over the course of 12 days, these treatments, 5 mM butyrate, 2% dimethyl sulfoxide, and serum withdrawal, all resulted in decreased levels of DNA synthesis and increased levels of H1o (in absolute terms and relative to the other H1 histones, H1abc). However, the increase in H1o differed comparing butyrate treatment, where there was a 6-fold increase in the H1o/H1abc ratio, with the other two treatments which both had only 3-fold increases in the H1o/H1abc ratio. The mechanism for increasing H1o differed for each of the three treatments and involved differential changes in both synthesis and degradation of the H1 subfractions to favor H1o accumulation on the chromatin. Despite the obvious correlation of the increase in H1o levels with the inhibition of DNA replication, we also showed that increases in H1o can occur without any change in DNA synthesis when cells are switched from media containing dimethyl sulfoxide to media with butyrate as the blocking agent. Finally, there was no correlation between the production of neurites in this cell line and H1o accumulation, arguing against simple, direct involvement of H1o in differentiation.


Measurement of dabigatran and rivaroxaban in primary prevention of venous thromboembolism in 106 patients, who have undergone major orthopedic surgery: an observational study.
No routine coagulation laboratory test is recommended during rivaroxaban or dabigatran treatment. However measuring drug concentration and/or anticoagulant activity can be desirable in some special clinical settings, such as bleeding, thrombosis recurrence or emergency surgery. The effects of dabigatran etexilate and rivaroxaban on various coagulation assays have been previously studied in normal plasma spiked with increasing concentrations of the drug. In contrast, few data are available in routinely treated patients. In order to perform and to interpret the results of these tests, it is necessary to determine the usual responses of patient's plasma. We have used several coagulation tests in a prospective study including 106 patients receiving thromboprophylactic treatment with dabigatran 150 or 220 mg od and rivaroxaban 10 mg od for major orthopaedic surgery. The most common tests--prothrombin time (PT) and activated partial thromboplastin time (aPTT)--give results, which vary according to the reagent used. To overcome this limitation, we advocate the use of plasma calibrators, which decreases the inter-laboratory heterogeneity of results. Anti-Xa measurement and Hemoclot, a thrombin diluted clotting assay, are specific assays which have been proposed for rivaroxaban and dabigatran respectively. These tests, conventional PT, aPTT and thrombin generation (TG) have been performed. We demonstrated that measurements of both drugs can determine reliably the drug concentration in patients' plasmas. PT is more prolonged with rivaroxaban than with dabigatran. Interestingly, the pattern of TG was clearly different in relation to the difference in the mechanism of action of the two new anticoagulants. A significant inter-individual variability of response is detected. Rivaroxaban--mean Cmax 140 ng/mL (extremes 0-412) induces a greater increase of PT than dabigatran. aPTT is sensitive to dabigatran. Rivaroxaban concentrations were in good agreement with two other studies while unexplained lower than expected concentrations were found in dabigatran patients receiving 220 mg once a day [mean Cmax 60 ng/mL (extremes 0-320)]. An interference by pantoprazole, a drug which reduces dabigatran absorption, could explain the observed lower than expected results.


[Preparation and identification of monoclonal antibodies against SARS-CoV putative protein X4].
To obtain monoclonal antibodies against putative protein X4 of SARS-CoV for further study of the structure and function of protein X4. Balb/c mice were immunized with recombinant Protein X4, hybridoma cell lines secreting monoclonal antibodies against protein X4 were screened by regular cell fusion and subcloning approach. The specificities of these monoclonal antibodies were determined by Western blotting and Immunofluorescence assay. Three hybridoma cell lines (8A5, 8H6 and 4A2) stable in secreting specific monoclonal antibodies were successfully obtained. They could bind specifically to protein X4 proved by Western blotting. All of them belonged to the IgG2a isotype proved by antigen mediated ELISA. Indirect Immunofluorescence assay indicated that they could specifically bind to protein X4 expressed in SARS-CoV infected Vero E6 cells. Monoclonal antibodies of high specificity against protein X4 have been successfully prepared, which laid the foundation for the further study of protein X4.


A high-molecular mass derivative of trypsin-kallikrein inhibitor for potential medical use. II. Study of inhibitory activity.
Three derivatives of poly[alpha-N beta-(2-hydroxyethyl)-DL-asparagine, beta-N alpha-(2-hydroxyethyl)-DL-asparagine] were used as soluble carrier polymers for binding the trypsin-kallikrein inhibitor (TKI). In addition to the parent polymer an anionic derivative with 19.2 mol of carboxyl groups/100 mol of residues and a hydrophobized derivative with 18.0 mol of butyl groups/100 mol of residues were also used. All carriers contained 6.6 mol of 2-(4-aminobenzamido)ethyl residues/100 mol which were used for the binding after diazotation. All derivatives retained a high inhibitory activity toward trypsin and chymotrypsin whereas the effect on kallikrein was substantially reduced. The kinetic constants were estimated under the simplifying assumption, that classical kinetic equations for the enzyme-inhibitor interaction may be applied. The equilibrium dissociation constants (5 X 10(-9) mol/l) and association rate constants (1 X 10(5) l X mol-1 X s-1) with respect to trypsin are unaffected by the two chemical modifications of the carrier. The increase in the equilibrium dissociation constant (compared to native TKI) is probably a result of the decreasing strength of the enzyme-inhibitor complex rather than a manifestation of reduced rate of diffusion of the enzyme to the active center of the polymer-bound inhibitor.


Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension.
Inflammatory cytokines may affect pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH). CC chemokine ligand 2 (CCL2) is synthesized by vascular cells and can stimulate monocyte/macrophage migration and smooth muscle cell (SMC) proliferation. To investigate the role of CCL2 in IPAH. CCL2 levels in plasma, monocytes, lungs, and medium from pulmonary endothelial cell (P-EC) or pulmonary artery SMC (PA-SMC) cultures were measured by ELISA and Western blot analysis. CCL2 receptor CCR2 mRNA levels in monocytes, P-ECs, and PA-SMCs were measured by real-time polymerase chain reaction. Effect of CCL2 on PA-SMC proliferation and migration was assessed using [3H]thymidine incorporation and a modified Boyden's chamber. The effect of endothelial cell-derived CCL2 on monocyte migration was measured using a modified Boyden's chamber. Compared with control subjects, we found the following in patients with IPAH: elevated CCL2 protein levels in plasma and lung tissue, whereas monocyte CCL2 levels were similar between patients and control subjects, and elevated CCL2 release by P-ECs or PA-SMCs. P-ECs released twice as much CCL2 than did PA-SMCs. Monocyte migration was markedly increased in the presence of P-ECs, and the increase was larger with P-ECs from patients with IPAH. CCL2-blocking antibodies reduced P-ECs' chemotactic activity by 60%. Compared with controls, PA-SMCs from patients exhibited stronger migratory and proliferative responses to CCL2, in keeping with the finding that CCR2 was markedly increased in PA-SMCs from patients. These results suggest that CCL2 overproduction may be a feature of the abnormal P-EC phenotype in IPAH, contributing to the inflammatory process and to pulmonary vascular remodeling.


Association of Demyelinating and Inflammatory Bowel Diseases: A Case Series and Overview of the Literature.
Neurological complications of inflammatory bowel diseases (i.e., ulcerative colitis and Crohn's disease) can be summarized as a combination of neuromuscular manifestations, cerebrovascular and demyelinating diseases that can be seen in approximately 3% of patients. In addition, asymptomatic cerebral white matter lesions may be detected in these patients. Clustering of diseases within families may be explained by the exposure to similar environmental factors, shared genes, or complex interactions between genetic and environmental factors. Here we report an epileptic patient with Crohn's disease and cerebral white matter lesions, a family with ulcerative colitis and multiple sclerosis and two patients who have both multiple sclerosis and Crohn's disease.


Discovery of 1,4-Benzodiazepine-2,5-dione (BZD) Derivatives as Dual Nucleotide Binding Oligomerization Domain Containing 1/2 (NOD1/NOD2) Antagonists Sensitizing Paclitaxel (PTX) To Suppress Lewis Lung Carcinoma (LLC) Growth in Vivo.
Nucleotide-binding oligomerization domain-like receptors (NLRs) are intracellular sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Previously, we reported nucleotide-binding oligomerization domain-containing protein 1 (NOD1) antagonists (11, 12) and a NOD2 antagonist (9) that sensitized docetaxel (DTX) or paclitaxel (PTX) treatment for breast or lung cancer. In this article, we describe for the first time a 1,4-benzodiazepine-2,5-dione (BZD) derivative (26bh) that acts as a dual NOD1/NOD2 antagonist and inhibits both nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory signaling, thereby sensitizing PTX to suppress Lewis lung carcinoma (LLC) growth. After investigation of the compound's cytotoxicity, a systematic structure-activity relationship (SAR) was completed and revealed several key factors that were necessary to maintain antagonistic ability. This study establishes the possibility for using adjuvant treatment to combat cancer by antagonizing both NOD1 and NOD2 signaling.


Bone response to jumping is site-specific in children: a randomized trial.
Skeletal loading during growth may be one way of increasing bone mass early in life. We hypothesized that children randomized to a jumping program (25 jumps/day from a 45-cm box, 5 days/week for 12 weeks) would have greater increases in hip and spine bone mineral content (BMC) and 4% distal tibia volumetric bone density than children randomized to the control group. Our secondary hypothesis was that jumping would not be as beneficial among peripubertal children as compared to prepubertal or pubertal children due to the relatively high growth rate that occurs during the peripubertal period. Fifty-four children (31 girls) ages 3-5, 7-8, 11-12, and 15-18 years were enrolled. We performed bone, anthropometric, and force plate measurements at baseline and 12 weeks. Twenty-four-hour diet recall and Tanner's self-report of pubertal development were completed at baseline. Jumpers had a lower calcium intake than nonjumpers at baseline (965 +/- 403 vs 1295 +/- 465 mg/day, P < 0.01), but the groups were otherwise similar. Overall, jumpers had greater increases in total body BMC (45.0 +/- 4.9 vs 29.4 +/- 5.3 g, P = 0.03) and regional dual energy x-ray absorptiometry leg BMC (19.8 +/- 2.6 vs 11.5 +/- 2.8 g, P = 0.03) than nonjumpers at all pubertal stages. However, the 4% distal tibia bone response to jumping appeared to be modified by pubertal stage, with the greatest bone benefit from jumping observed in pubertal children (interaction of jumping group by pubertal stage, P < 0.05, for both BMC and volumetric BMD). A similar pattern was observed for spine BMC (interaction, P = 0.10). We conclude that skeletal loading increases total body and leg BMC in children, but may not have a positive effect at sites that are predominantly trabecular bone during periods of rapid growth (i.e., peripubertal period).


[Clinical observation on chronic severe hepatitis B treated by principles of cooling-blood and detoxicating combined with clearing-heat and resolving-damp or combined with strengthening-Pi and warming-yang].
To observe the therapeutic efficacy on chronic severe hepatitis B (CSH) patients of Yanghuang and Yinhuang syndrome type by principles of cooling-blood and detoxicating combined with clearing-heat and resolving dampness (PA) or with strengthening-Pi and warming-yang (PB), respectively. Forty-three patients with CSH were randomly divided into two groups, group A (22 cases) treated with PA and group B (21 cases) with PB. The therapeutic efficacy, laying stress on the effect in eliminating jaundice, was observed. The efficacy in group B was effective in 19 cases (90.5%), and ineffective in 2 (9.5%), while in group A, effective in 16 (72.7%) and ineffective in 6 (27.3%). Levels of TBIL and ALT were significantly lower in both groups (P < 0.05 or P < 0.01), and the descending extent was greater, the thrombinogen activity was higher in group B than that in group A after treatment (P < 0.05), no significant difference in ALT was found between the two groups. The efficacy of PB is better than that of PA on CSH with Yanghuang and Yinghuang syndrome.


Disseminated cryptococcosis with recurrent multiple abscesses in an immunocompetent patient: a case report and literature review.
Cryptococcus neoformans is frequently present as an opportunistic pathogen mainly affecting immunocompromised populations. Disseminated C. neoformans infection in immunocompetent population is rare and usually involves lung and central nerve system. Cryptococcus from biologic samples can easily grow on routine fungal and bacterial culture media. Besides, cryptococcal latex agglutination test has been established as a reliable diagnostic tool with overall sensitivities of 93-100%. We report a rare disseminated cryptococcosis case which presented with chronic recurrent multiple abscess in an immunocompetent male involving skin, lung, spine and iliac fossa without evidence of central nerve system involving. The results of serum cryptococcal latex agglutination tests and standard microbial cultures were negative. The patient underwent empirical anti-bacterial and anti-tuberculosis therapy which turned out to be effectless. Finally, bedside inoculation of the pus was carried out and revealed Cryptococcus neoformans, which was confirmed by polymerase chain reaction. After the administration of anti-fungal drugs including liposomal amphotericin B, the patient recovered from fever and paraplegia. This case reveals an uncommon pattern of disseminated C. neoformans infection in immunocompetent population presented with chronic multiple abscess and without central nerve system involving. Negative routine microbial cultures may not necessarily rule out cryptococcosis, especially in early stage. Besides, cryptococcal latex agglutination test does have a chance of false negative, which might be related with "capsule-deficiency". Moreover, this phenomenon could be related with low-grade virulence and relative long illness duration.


A neuroscience approach to managing athletes with low back pain.
Low back pain (LBP) is a common complaint within the athletic population and is commonly managed through a biomedical approach. The injured or damaged structure causing the LBP is identified and treated, and complete recovery from the episode is expected. Clinical experience shows us that often, athletes with LBP will not recover from their episode and may continue their sports participation despite persistent pain, or they may limit participation. Recent neuroscience research into the biology of pain suggests that clinicians involved in the management of athletes with LBP should embrace a biopsychosocial approach by engaging the brain and nervous system. This manuscript provides an overview of such a biopsychosocial approach, and presents information on the neurobiology of the athlete's pain experience.


The A protein of the filamentous bacteriophage Cf of Xanthomonas campestris pv. citri.
Filamentous bacteriophages have very strict host specificities. Experiments were performed to investigate whether the A protein of the filamentous phage Cf, which infects Xanthomonas campestris pv. citri but not X. campestris pv. oryzae, is involved in determining Cf's host specificity. The gene encoding the A protein of Cf was cloned and expressed in X. campestris pv. citri. The genomic DNA of another filamentous bacteriophage, Xf, which infects X. campestris pv. oryzae but not X. campestris pv. citri, was then introduced by electroporation into X. campestris pv. citri that had expressed the A protein of Cf. The progeny phages thus produced were able to infect both X. campestris pv. oryzae and X. campestris pv. citri, indicating that the A protein of Cf was incorporated into the viral particles of Xf and conferred upon Xf the ability to infect the host of Cf. Inactivation of the A protein gene abolished the infectivity of Cf. The results of this study indicate that the A protein of Cf is responsible for controlling the host specificity of Cf.


Beyond the antibody: B cells as a target for bacterial infection.
It is well established that B cells play an important role during infections beyond antibody production. B cells produce cytokines and are APCs for T cells. Recently, it has become clear that several pathogenic bacterial genera, such as Salmonella, Brucella, Mycobacterium, Listeria, Francisella, Moraxella, and Helicobacter, have evolved mechanisms such as micropinocytosis induction, inflammasome down-regulation, inhibitory molecule expression, apoptosis induction, and anti-inflammatory cytokine secretion to manipulate B cell functions influencing immune responses. In this review, we summarize our current understanding of B cells as targets of bacterial infection and the mechanisms by which B cells become a niche for bacterial survival and replication away from extracellular immune responses such as complement and antibodies.


Contrasting effects of reward expectation on sensory and motor memories in primate prefrontal neurons.
The value of reward obtained with successful behavior is important for guiding purposeful behavior. The lateral prefrontal cortex (LPFC) has been implicated in working memory that guides goal-directed behavior. However, mechanism that integrates the reward value into the working memory for goal-directed behavior is not understood. To help clarify this issue, we examined the effect of reward expectation on the neuronal process in the LPFC associated with memory-based sensorimotor processing. By temporally dissociating visuospatial sensory and saccade-directional motor memories in the LPFC, we here show that reward expectation significantly enhanced the directional selectivity of sensory working memory but did not affect the directional selectivity of motor memory. The enhancement of sensory working memory in the neuronal population was sustained during the delay but extinguished soon after the motor memory appeared. These results suggest that the expectation of high reward value primarily affects the sensory working memory that may be used for behavioral guidance rather than preparation for forthcoming saccades. It thus appears that the LPFC is a neuronal substrate for working memory used to guide a reward-oriented behavior, rather than reflecting an efficient control of motor action in motivated states.


Meta-analysis of genetic-linkage analysis of quantitative-trait loci.
Meta-analysis is an important tool in linkage analysis. The pooling of results across primary linkage studies allows greater statistical power to detect quantitative-trait loci (QTLs) and more-precise estimation of their genetic effects and, hence, yields conclusions that are stronger relative to those of individual studies. Previous methods for the meta-analysis of linkage studies have been proposed, and, although some methods address the problem of between-study heterogeneity, most methods still require linkage analysis at the same marker or set of markers across studies, whereas others do not result in an estimate of genetic variance. In this study, we present a meta-analytic procedure to evaluate evidence from several studies that report Haseman-Elston statistics for linkage to a QTL at multiple, possibly distinct, markers on a chromosome. This technique accounts for between-study heterogeneity and estimates both the location of the QTL and the magnitude of the genetic effect more precisely than does an individual study. We also provide standard errors for the genetic effect and for the location (in cM) of the QTL, using a resampling method. The approach can be applied under other conditions, provided that the various studies use the same linkage statistic.


Inhibition of hypoxia-induced cyclooxygenase-2 by Korean Red Ginseng is dependent on peroxisome proliferator-activated receptor gamma.
Korean Red Ginseng (KRG) is a traditional herbal medicine made by steaming and drying fresh ginseng. It strengthens the endocrine and immune systems to ameliorate various inflammatory responses. The cyclooxygenase-2 (COX-2)/prostaglandin E2 pathway has important implications for inflammation responses and tumorigenesis. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates not only adipogenesis and lipid homeostasis, but also angiogenesis and inflammatory responses. The effects of the KRG on inhibition of hypoxia-induced COX-2 via PPARγ in A549 cells were determined by luciferase assay, Western blot, and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The antimigration and invasive effects of KRG were evaluated on A549 cells using migration and matrigel invasion assays. We previously reported that hypoxia-induced COX-2 protein and mRNA levels were suppressed by KRG. This study examines the possibility of PPARγ as a cellular target of KRG for the suppression of hypoxia-induced COX-2. PPARγ protein levels and PPARγ-responsive element (PPRE)-driven reporter activities were increased by KRG. Reduction of hypoxia-induced COX-2 by KRG was abolished by the PPARγ inhibitor GW9662. In addition, the inhibition of PPARγ abolished the effect of KRG on hypoxia-induced cell migration and invasion. Our results show that KRG inhibition of hypoxia-induced COX-2 expression and cell invasion is dependent on PPARγ activation, supporting the therapeutic potential for suppression of inflammation under hypoxia. Further studies are required to demonstrate whether KRG activates directly PPARγ and to identify the constituents responsible for this activity.


Machine Learning Consensus To Predict the Binding to the Androgen Receptor within the CoMPARA Project.
The nuclear androgen receptor (AR) is one of the most relevant biological targets of Endocrine Disrupting Chemicals (EDCs), which produce adverse effects by interfering with hormonal regulation and endocrine system functioning. This paper describes novel in silico models to identify organic AR modulators in the context of the Collaborative Modeling Project of Androgen Receptor Activity (CoMPARA), coordinated by the National Center of Computational Toxicology (U.S. Environmental Protection Agency). The collaborative project involved 35 international research groups to prioritize the experimental tests of approximatively 40k compounds, based on the predictions provided by each participant. In this paper, we describe our machine learning approach to predict the binding to AR, which is based on a consensus of a multivariate Bernoulli Naive Bayes, a Random Forest, and N-Nearest Neighbor classification models. The approach was developed in compliance with the Organization of Economic Cooperation and Development (OECD) principles, trained on 1687 ToxCast molecules classified according to 11 in vitro assays, and further validated on a set of 3,882 external compounds. The models provided robust and reliable predictions and were used to gather novel data-driven insights on the structural features related to AR binding, agonism, and antagonism.


Complete Obstruction of Endotracheal Tube in an Infant with a Retropharyngeal and Anterior Mediastinal Abscess.
Intraoperative ventilatory failure is not an uncommon complication; however, acute endotracheal obstruction by a foreign body or blood clot can be difficult to quickly discriminate from other causes. Once the diagnosis is made, quick action is needed to restore ventilation. The ultimate solution is to exchange the endotracheal tube; however, there can be other ways of resolving this in situations where reintubation would be difficult or unsafe. This case report discusses such an event in an infant with multiple airway challenges including a retropharyngeal and anterior mediastinal abscess. We have also formulated a pathway based on various case reports involving complete ETT obstruction.


Gender inequalities in maternal perception of healthy child body shape and their association with child body mass and blood pressure.
To investigate whether maternal perception of child body shape is different for boys and girls and whether this subjective parameter is associated with objective indices of cardiovascular health. Cross-sectional survey (the ARCA Project). Southern Italy. Body mass index, waist circumference and blood pressure were measured according to standardised procedures in 3551 children (Boys = 1778; Girls = 1773) aged 6-11 years. Maternal perception of child body shape was investigated by inviting mothers to choose, within two sets of seven, 9-year-old child silhouettes (one set for boys and one set for girls), the body shape they perceived as that of a healthy child. Although the majority of mothers indicated the median silhouette as 'healthy', mothers of girls chose a fatter silhouette as 'healthy' more often than the mothers of boys (P = 0.001). By regression analysis, mothers' perception of a child's body shape was a significant determinant (P < 0.01) of blood pressure in both genders, and of anthropometric indices in girls only, independently of parental overweight, education, birth weight and physical activity. Our study suggests that maternal perception of a healthy body shape in children is associated with her child's blood pressure and degree of adiposity; with regard to the latter, differences between genders are apparent.


Retransplantation after BK virus nephropathy in prior kidney transplant: an OPTN database analysis.
BK virus (BKV) has emerged as a major complication of kidney transplantation. Since June 30, 2004, the OPTN in the USA collects BKV as a primary or secondary cause of graft loss and also if treatment for BK virus (TBKV) is administered. In this study, we determined characteristics of those recipients of repeat kidney transplants from the OPTN database, where either (a) a graft loss occurred between June 30, 2004 and December 31, 2008 and database recorded prior TBKV in that allograft or (b) a graft loss between June 30, 2004 and December 31, 2008 was attributed primarily or secondarily due to BKV. In the study time period, 823 graft losses have occurred where TBKV or graft failure attributable to BKV was reported in prior transplant; of these, 126 have received a retransplant as of June 5, 2009. Induction and maintenance immunosuppression usage mirrored current trends. As of June 5, 2009, 118/126 grafts are still functioning, one graft failure attributed to BKV. TBKV was reported in 17.5% of the retransplants. In the retransplants performed through December 31, 2007, 1-year acute rejection rate was 7%, 1-year and 3-year Kaplan-Meier graft survival rates and median GFR were 98.5%, 93.6%, 65.5 and 68.4 mL/min, respectively. Retransplantation after BKV appears to be associated with good results.


Improving access to home phototherapy for patients with psoriasis: current challenges and future prospects.
Although the treatment burden for phototherapy in the outpatient setting is considerable, prescription of home-based phototherapy has not been instigated. Home-based phototherapy seems more patient friendly in terms of avoiding the thrice-weekly hospital visits. So why are most treatments still given in a hospital setting? Is home-based treatment less effective? Are there financial barriers? Is the treatment not available? To answer these questions, a literature search was done. A literature search of PubMed, Embase, and Cochrane Library databases was performed, using the search terms "psoriasis" and "phototherapy". Selection was based on two rounds; the first round involved screening the title and abstract of all records and second involved evaluating the full text of the remaining articles for eligibility according to inclusion and exclusion criteria. In total, 23 publications were included with consensus of both researchers. Overall, the patients reported being very satisfied with home-based phototherapy. Results regarding effectivity in terms of improvement from disease severity and in quality of life were variable but generally positive. Reasons for reluctance varied from medicolegal and social aspects to lack of reimbursement and unfamiliarity on the side of the prescriber. In the treatment for psoriasis, home-based phototherapy is as effective and safe as phototherapy in an outpatient setting. Patients were more satisfied with home-based phototherapy. Factors that negatively influence the prescription of or choice for home-based phototherapy can be summarized in terms of lack of control, lack of knowledge, and lack of a good reimbursement system.


Strabismus in patients with neurofibromatosis type 1-associated optic pathway glioma.
To characterize the incidence, type, natural history, and treatment outcomes of strabismus in pediatric patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). The medical records of consecutive patients diagnosed with NF1 and OPG at our neurofibromatosis clinic since 1985 were reviewed retrospectively. We noted age at diagnosis, reason for referral to our clinic, ophthalmologic examination results, presence or absence of strabismus, strabismus type and treatment, and final results of treatment. A total of 76 patients were included. Of these, 22 (28.9%) had strabismus: 5 (22.7%) had esotropia and 17 (77.2%) had exotropia; of those with exotropia, 10 (45%) also had hypotropia. In 12 patients (54.5%), strabismus was present at the first ophthalmologic examination. The development of strabismus preceded the diagnosis of both NF1 and OPG in 4 (5.3%) patients and the diagnosis of OPG in another 2 (2.6%) patients with known NF1. In 16 (76%) patients, the strabismus was sensory. Five patients (22.7%) underwent surgery, which resulted in a deviation angle of <10(Δ) in 1 patient, <20(Δ) in 2 patients, and >20(Δ) in 2 patients. Strabismus was the presenting symptom and led to the diagnosis of OPG in a subset of patients, including those who did not have a previous diagnosis of NF1. Exotropia, especially associated with a hypotropia, was the most common strabismic deviation seen in these patients. Sensory strabismus was the most common type seen in this population. Deviations of <10(Δ) may be difficult to achieve with strabismus surgery.


SLM, a novel carbazole-based fluorophore attenuates okadaic acid-induced tau hyperphosphorylation via down-regulating GSK-3β activity in SH-SY5Y cells.
Phosphorylated tau dissociates from microtubules and aggregates to form neurofibrillary tangles resulting in neuronal toxicity and cognitive deficits. Attenuating tau hyperphosphorylation is considered as an effective therapeutic approach for Alzheimer's disease (AD). From our previous study, SLM, a carbazole-based fluorophore prevents Aβ aggregation, reduced glycogen synthase kinase-3β (GSK-3β) activity and tau hyperphosphorylation in triple transgenic mouse model of AD. However, the mechanism by which SLM attenuates tau hyperphosphorylation warrants further investigation. In the current study, we intend to evaluate the effects of SLM against okadaic acid (OA)-induced tau hyperphosphorylation and microtubules instability in human neuroblastoma (SH-SY5Y) cells. The results showed that, SLM reduced the OA-induced cell neurotoxicity and tau hyperphosphorylation in SH-SY5Y cells. SLM treatment down-regulated GSK-3β activity. However, in the presence of GSK-3β inhibitor (SB216763, 10μM), SLM treatment could not reduce GSK-3β activity and tau hyperphosphorylation as compared with SB216763 treatment alone. Furthermore, SLM treatment also ameliorated OA-induced microtubules instability and cytoskeleton damage. Collectively, SLM attenuated OA-induced tau hyperphosphorylation via down-regulating GSK-3β activity in SH-SY5Y cells. Therefore, this study supports SLM as a potential compound for AD and other tau pathology-related neurodegenerative disorders.


Indirect Fitness Benefits Enable the Spread of Host Genes Promoting Costly Transfer of Beneficial Plasmids.
Bacterial genes that confer crucial phenotypes, such as antibiotic resistance, can spread horizontally by residing on mobile genetic elements (MGEs). Although many mobile genes provide strong benefits to their hosts, the fitness consequences of the process of transfer itself are less clear. In previous studies, transfer has been interpreted as a parasitic trait of the MGEs because of its costs to the host but also as a trait benefiting host populations through the sharing of a common gene pool. Here, we show that costly donation is an altruistic act when it spreads beneficial MGEs favoured when it increases the inclusive fitness of donor ability alleles. We show mathematically that donor ability can be selected when relatedness at the locus modulating transfer is sufficiently high between donor and recipients, ensuring high frequency of transfer between cells sharing donor alleles. We further experimentally demonstrate that either population structure or discrimination in transfer can increase relatedness to a level selecting for chromosomal transfer alleles. Both mechanisms are likely to occur in natural environments. The simple process of strong dilution can create sufficient population structure to select for donor ability. Another mechanism observed in natural isolates, discrimination in transfer, can emerge through coselection of transfer and discrimination alleles. Our work shows that horizontal gene transfer in bacteria can be promoted by bacterial hosts themselves and not only by MGEs. In the longer term, the success of cells bearing beneficial MGEs combined with biased transfer leads to an association between high donor ability, discrimination, and mobile beneficial genes. However, in conditions that do not select for altruism, host bacteria promoting transfer are outcompeted by hosts with lower transfer rate, an aspect that could be relevant in the fight against the spread of antibiotic resistance.


Advancements in Neighboring-Based Energy-Efficient Routing Protocol (NBEER) for Underwater Wireless Sensor Networks.
Underwater wireless sensor networks (UWSNs) have gained prominence in wireless sensor technology, featuring resource-limited sensor nodes deployed in challenging underwater environments. To address challenges like power consumption, network lifetime, node deployment, topology, and propagation delays, cooperative transmission protocols like co-operative (Co-UWSN) and co-operative energy-efficient routing (CEER) have been proposed. These protocols utilize broadcast capabilities and neighbor head node (NHN) selection for cooperative routing. This research introduces NBEER, a novel neighbor-based energy-efficient routing protocol tailored for UWSNs. NBEER aims to surpass the limitations of Co-UWSN and CEER by optimizing NHNS and cooperative mechanisms to achieve load balancing and enhance network performance. Through comprehensive MATLAB simulations, we evaluated NBEER against Co-UWSN and CEER, demonstrating its superior performance across various metrics. NBEER significantly maximizes end-to-end delay, reduces energy consumption, improves packet delivery ratio, extends network lifetime, and enhances total received packets analysis compared to the existing protocols.


Surgical treatment for acute small intestinal obstruction caused by Parascaris equorum infection in 15 horses (2002-2011).
There is a consensus in the veterinary literature that Parascaris equorum (ascarid) impaction carries a poor prognosis. Hence surgery is often delayed and foals are often subjected to euthanasia after diagnosis of ascarid impaction is established. Our clinical impression was that ascarid impaction carries a better prognosis than previously reported. Our expectation was that manually evacuating the impaction into the caecum, thus refraining from opening the small intestine, would improve the prognosis for survival of horses with ascarid impaction. The aim of this study was to examine medical records of horses treated surgically for ascarid impaction, record their clinical findings and evaluate the association of outcome with the method of relieving the impaction. The medical records of all horses presented to our hospital between October 2002 and December 2011 that underwent exploratory celiotomy for ascarid impaction were reviewed. Information retrieved from the medical record included surgical findings, surgical technique, complications, short- and long-term survival. The association between categorical variables was assessed using the Fisher's exact test. A P value < 0.05 was considered statistically significant. Fifteen horses fulfilled the inclusion criteria. Eighty percent of horses (12/15) survived to discharge and 60% (6/10) survived for at least one year. Five horses are doing well but are still in convalescence. Horses that underwent small intestinal enterotomy or resection and anastomosis (n = 5) were less likely to survive to discharge (P = 0.022). In our study, manual evacuation of ascarid impaction into the caecum, while refraining from opening the small intestine resulted in significantly improved survival in horses with ascarid impaction. Refraining from opening the small intestine may be the key to improving surgical outcome in horses with ascarid impaction.


Post-transplant infections: single center experience from the developing world.
To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.


Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.
To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.


Analysis of human papillomavirus type 18 load and integration status from low-grade cervical lesion to invasive cervical cancer.
The clinical value of viral load and integration testing for human papillomavirus (HPV) remains unclear. Data on HPV type 18 (HPV18) is limited. We examined the HPV18 viral load and integration status of 78 women with normal cervix or neoplasia. While the crude viral load appeared to increase with lesion severity, the association was not significant after normalization with sample cellularity. Unlike reports for HPV16, the amino-terminal 1 region of HPV18 E2 was most frequently (71.0%) disrupted, representing the best marker for integration. A substantial proportion (57.1%) of invasive cancers harbored only the episomal genome, thus jeopardizing the clinical value of integration testing. A large proportion (41.7%) of normal/low-grade lesions showed viral integration, suggesting that integration of HPV18 starts early and is unlikely to be a sole determinant for progression. Interpretation of viral load should take into account the form of HPV infection as single infections had significantly higher viral loads than coinfections (P = 0.046). More data generated from routinely collected samples are warranted to verify the clinical value of viral load and integration testing. Viral load quantitation for HPV18 is premature for clinical use at this stage.


Exercise testing criteria to diagnose lower extremity peripheral artery disease assessed by computed-tomography angiography.
The sensitivity and specificity of exercise testing have never been studied simultaneously against an objective quantification of arterial stenosis. Aims were to define the sensitivity and specificity of several exercise tests to detect peripheral artery disease (PAD), and to assess whether or not defined criteria defined in patients suspected of having a PAD show a difference dependent on the resting ABI. In this prospective study, consecutive patients with exertional limb pain referred to our vascular center were included. All patients had an ABI, a treadmill exercise-oximetry test, a second treadmill test (both 10% slope; 3.2km/h speed) with post-exercise pressures, and a computed-tomography-angiography (CTA). The receiver-operating-characteristic curve was used to define a cut-off point corresponding to the best area under the curve (AUC; [CI95%]) to detect arterial stenosis ≥50% as determined by the CTA. Sixty-three patients (61+/-11 years-old) were included. Similar AUCs from 0.72[0.63-0.79] to 0.83[0.75-0.89] were found for the different tests in the overall population. To detect arterial stenosis ≥50%, cut-off values of ABI, post-exercise ABI, post-exercise ABI decrease, post-exercise ankle pressure decrease, and distal delta from rest oxygen pressure (DROP) index were ≤0.91, ≤0.52, ≥43%, ≥20mmHg and ≤-15mmHg, respectively (p<0.01). In the subset of patients with an ABI >0.91, cut-off values of post-exercise ABI decrease (AUC = 0.67[0.53-0.78]), and DROP (AUC = 0.67[0.53-0.78]) were ≥18.5%, and ≤-15mmHg respectively (p<0.05). Resting ABI is as accurate as exercise testing in patients with exertional limb pain. Specific exercise testing cut-off values should be used in patients with normal ABI to diagnose PAD.


Atomic layer deposition in nanometer-level replication of cellulosic substances and preparation of photocatalytic TiO2/cellulose composites.
TiO2 replicas of filter paper with nanometer-level accuracy were prepared by atomic layer deposition of thin conformal TiO2 coating, followed by a removal of the paper by air-anneal at 450 degrees C. Photocatalytic anatase TiO2/cellulose composites were also made by leaving the paper intact. The TiO2 films were deposited from Ti(OMe)4 and H2O at 150-250 degrees C. The photocatalytic activity of the TiO2/cellulose composite was verified by photocatalytic reduction of Ag(I) from an aqueous solution to Ag nanoparticles on the TiO2 surface. The TiO2/cellulose composites are mechanically more stable than the free-standing TiO2 replicas and are therefore potentially suitable as lightweight, high surface area photocatalysts.


Antibody-mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice.
Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg2+ balance in patients and only have a mild effect on Mg2+ homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (Pi) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at Pi excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg2+ and/or Pi in the kidney remains controversial. Here, we inject mice with the anti-EGFR monoclonal antibody ME-1 for 2 weeks and observe a significant increase in serum Pi and mild hypomagnesemia, but no changes in Pi or Mg2+ excretion. In contrast, a single injection of ME-1 resulted in hyperphosphatemia and a significant reduction in Pi excretion 2 days after treatment, while no changes in serum Mg2+ or Mg2+ excretion were observed. Dietary Mg2+ deprivation is known to trigger a rapid Mg2+ conservation response in addition to hyperphosphatemia and hyperphosphaturia. Interestingly, one dose of ME-1 did not significantly modify the response of mice to 2 days of Mg2+ deprivation. These data show that EGFR plays a significant role in regulating Pi reabsorption in the kidney PCT, but suggest only a minor role in long-term regulation of Mg2+ transport in the distal convoluted tubule.


Effect of 2% Chlorhexidine Gluconate-Impregnated Cloth on Surgical Site Infections in Vascular Surgery.
Surgical site infections (SSIs) are a significant burden to patients and health care systems. This retrospective study evaluates the observed rates of SSI after our institution implemented chlorhexidine gluconate-impregnated (CHG) cloth as a preoperative antiseptic preparation in elective vascular surgery. Between March 2011 and January 2012, we reviewed 250 patients who underwent elective vascular surgery who used the CHG cloth preoperatively. Their rate of SSIs was compared with 252 control patients who received the CHG shower preoperatively during the preintervention period. Urgent and emergent cases were excluded. The primary outcome measured was SSI within 30 days of index operation. There was no baseline difference in mean age, gender distribution, smoking status, diabetes, chronic obstructive pulmonary disease, and the number of patients with body mass index >40 between the cohorts. There was no difference in the overall rate (5.6% vs. 5.6%, P = 1.00) and type of SSIs between the 2 groups, but the control group trended toward deeper infections (4 deep incisional and 2 organ space vs. none and 1, respectively). The control group also had more dirty or infected wound categories (10 vs. 21.4%, P < 0.01) and more perioperative antibiotic errors and hypothermia (P < 0.02). There was no observed difference in SSI rates before and after implementation of the CHG as the preoperative method of skin decontamination in our retrospective case-control cohorts.


Insular dysfunction of interoception in major depressive disorder: from the perspective of neuroimaging.
Interoception plays a crucial role in maintaining bodily homeostasis and promoting survival, and is considered the basis of human emotion, cognition, and self-formation. A malfunction of interoception is increasingly suggested to be a fundamental component of different mental health conditions, and depressive disorders have been especially closely associated. Interoceptive signaling and processing depends on a system called the "interoceptive pathway," with the insula, located in the deep part of the lateral fissure, being the most important brain structure in this pathway. Neuroimaging studies have revealed alterations in the structure and function of the insula in a large number of individuals with depression, yet the precise relationship between these alterations and interoceptive dysfunction remains unclear. The goal of this review is to examine the evidence that exists for dysfunction of interoception in people with Major Depressive Disorder (MDD), and to determine the associated specific alterations in the structure and function of the insula revealed by neuroimaging. Overall, three aspects of the potential relationship between interoceptive dysfunction and alterations in insular function in people with depression have been assessed, namely clinical symptoms, quantitative measures of interoceptive function and ability, and interoceptive modulation. To conclude, several specific limitations of the published studies and important lines of enquiry for future research are offered.


The hidden crisis of nurse suicide.
This article discusses the epidemiology of suicide, the suicide rates among the general population and nurses, suicide risk factors and barriers to reporting mental health issues among healthcare professionals, strategies to recognize nurses at risk for suicide, and interventions to prevent nurse suicide.


The use of proton therapy in the treatment of head and neck cancers.
External beam radiation therapy is a commonly utilized treatment modality in the management of head and neck cancer. Given the close proximity of disease to critical normal tissues and structures, the delivery of external beam radiation therapy can result in severe acute and late toxicities, even when delivered with advanced photon-based techniques, such as intensity-modulated radiation therapy. The unique physical characteristics of protons make it a promising option in the treatment of advanced head and neck cancer, with the potential to improve sparing of normal tissues and/or safely escalate radiation doses. Clinical implementation will require the continued development of advanced techniques such as intensity-modulated proton therapy, using pencil beam scanning, as well as rigorous methods of quality assurance and adaptive techniques to accurately adjust to changes in anatomy due to disease response. Ultimately, the widespread adaptation and implementation of proton therapy for head and neck cancer will require direct, prospective comparisons to standard techniques such as intensity-modulated radiation therapy, with a focus on measures such as toxicity, disease control, and quality of life.


The anti-apoptotic and anti-oxidant effect of eriodictyol on UV-induced apoptosis in keratinocytes.
Recently, considerable scientific and therapeutic interest has focused on the structure and functions of the flavonoids. In a previous study, we suggested that hydroxyl (OH) substitutions on specific carbons in the skeleton of the flavonoids might significantly affect their apoptosis-modulating properties. Here, to investigate the effect of various OH substitutions on their diphenylpropane (C6C3C6) skeleton carbons, we selected 10 different flavonoids and assessed their role on UV-induced apoptosis of human keratinocytes, the principal cell type of epidermis. The results showed that 5,7,3',4'-tetrahydroxylflavanone (eriodictyol) and 3,4'-dihydroxy flavone (3,4'-DHF) had a positive effect on cell proliferation of human HaCaT keratinocytes. Treatment with eriodictyol in particular resulted in significant suppression of cell death induced by ultraviolet (UV) light, a major skin-damaging agent. We found that eriodictyol treatment apparently reduced the percentage of apoptotic cells and the cleavage of poly(ADP-ribose) polymerase, concomitant with the repression of caspase-3 activation and reactive oxygen species (ROS) generation. The anti-apoptotic and anti-oxidant effects of eriodictyol were also confirmed in UV-induced cell death of normal human epidermal keratinocyte (NHEK) cells. Taken together, these findings suggest that eriodictyol can be used to protect keratinocytes from UV-induced damage, implying the presence of a complex structure-activity relationship (SAR) in the differential apoptosis-modulating activities of various flavonoids.


Imaging in Vascular Access.
This review examines four imaging modalities; ultrasound (US), digital subtraction angiography (DSA), magnetic resonance imaging (MRI) and computed tomography (CT), that have common or potential applications in vascular access (VA). The four modalities are reviewed under their primary uses, techniques, advantages and disadvantages, and future directions that are specific to VA. Currently, US is the most commonly used modality in VA because it is cheaper (relative to other modalities), accessible, non-ionising, and does not require the use of contrast agents. DSA is predominantly only performed when an intervention is indicated. MRI is limited by its cost and the time required for image acquisition that mainly confines it to the realm of research where high resolution is required. CT's short acquisition times and high resolution make it useful as a problem-solving tool in complex cases, although accessibility can be an issue. All four imaging modalities have advantages and disadvantages that limit their use in this particular patient cohort. Current imaging in VA comprises an integrated approach with each modality providing particular uses dependent on their capabilities. MRI and CT, which currently have limited use, may have increasingly important future roles in complex cases where detailed analysis is required.


Effectiveness of early and aggressive administration of fresh frozen plasma to reduce massive blood transfusion during cytoreductive surgery.
Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been consistently associated with high volume blood loss and red blood cell (RBC) transfusion. This study evaluates the effectiveness of the introduction of a novel protocol to reduce blood loss and subsequent intra-operative transfusion in patients with high volume disease. One hundred and thirty-one consecutive patients with high volume disease (peritoneal cancer index ≥16) who underwent CRS and PIC were evaluated. Group I consisted of the sixty patients (46%) treated before June 2006. Group II consistent of the seventy-one (54%) patients treated after June 2006 under the new protocol. The clinical and treatment-related data of patients in the two groups were compared. Group II was associated with reduced intra-operative red blood cell transfusion (P<0.001), reduced cryoprecipitate transfusion (P=0.020), reduced platelet transfusion (P<0.001), reduced fresh frozen plasma transfusion (P=0.024), reduced operation length (P<0.001), reduced crystalloid administration (P<0.001) and reduced colloid administration (P<0.001). Group II was also associated with increased transfusion of FFP in the first half of the surgical intervention relative to the second half [FFP1(st)(:)FFP2(nd) ratio >1 (P<0.001)] and increased transfusion of RBC in the first half of the surgical intervention relative to the second half [RBC1(st)(:)RBC2(nd) ratio ≥1 (P=0.016)]. Early administration of fresh frozen plasma combined with restrictive fluid resuscitation may reduce overall intra-operative transfusion of RBC and other blood components.


No effect of energy supply during childbirth on delivery outcomes in nulliparous women: a randomised, double-blind, placebo-controlled trial.
The effect of providing oral energy supplements of energy on duration of labour and labour outcomes remains to be clarified. The purpose of this study was to examine whether extra energy supply beyond a self-regulated dietary intake during labour would shorten duration of labour in nulliparous women. A total of 213 healthy women at gestational age >36 weeks received either 1 litre of isotonic energy-drink (n = 111) or placebo-drink (n = 102) at the start of labour. A total of 61% in the intervention group gave birth within the hospital median of 9 hours, compared with 58% in the placebo group (p = 0.68). The mean (SD) durations of labour were 528 (240) minutes and 506 (233) minutes in the intervention and placebo group (p = 0.50), respectively. Extra oral supply of 1 litre energy drink beyond self-regulated intake of food and drink to healthy nulliparous women in birth does not affect the duration of labour.


[Kaufmann syndrome or VACTERL association? Discussion of a differential diagnosis].
The authors describe a dysmature female newborn, with multiple birth defects, who died soon after birth. At first polydactyly and hydrometrocolpos let think of a Kaufman syndrome, with autosomal recessive inheritance. But due to the presence of other malformations and since polydactyly is preaxial, the whole clinical and anatomical picture may be put into the frame of VACTERL association, mainly sporadic. Thus seemingly hydrometrocolpos and urogenital sinus have to be added, although rarely, to the other known defects of the VACTERL association.


Persistence Rate with Tadalafil for Treatment of Male Lower Urinary Tract Symptoms.
We examined the persistence rate with tadalafil for treatment of male lower urinary tract symptoms (LUTS) and explored the factors relevant to withdrawal. We retrospectively collected the data of male patients who received tadalafil treatment for LUTS. The persistence rate and the reason for withdrawal were investigated. A total of 155 patients were examined. Mean age and mean observation period were 71.9 (48-93) years and 15.1 (1-52) months, respectively. During the observation period, 74 patients (48%) withdrew tadalafil. The Kaplan-Meier curve indicated a 58% persistence rate at 1 year. The reasons for withdrawal included insufficient efficacy (31 patients, 42%), adverse events (21 patients, 28%), or symptom improvement (8 patients, 11%). Patients who continued tadalafil were significantly younger than those who withdrew it due to insufficient efficiency (71.4 ± 9.6 vs. 74.9 ± 9.1 years). Most patients withdrew tadalafil due to insufficient efficacy. Older patients are likely to withdraw the treatment because of insufficient efficacy, thus, tadalafil for male LUTS could be more effective for younger patients.


ADAMTS13 phenotype in plasma from normal individuals and patients with thrombotic thrombocytopenic purpura.
The activity of ADAMTS13, the von Willebrand factor cleaving protease, is deficient in patients with thrombotic thrombocytopenic purpura (TTP). In the present study, the phenotype of ADAMTS13 in TTP and in normal plasma was demonstrated by immunoblotting. Normal plasma (n = 20) revealed a single band at 190 kD under reducing conditions using a polyclonal antibody, and a single band at 150 kD under non-reducing conditions using a monoclonal antibody. ADAMTS13 was not detected in the plasma from patients with congenital TTP (n = 5) by either antibody, whereas patients with acquired TTP (n = 2) presented the normal phenotype. Following immunoadsorption of immunoglobulins, the ADAMTS13 band was removed from the plasma of the patients with acquired TTP, but not from that of normal individuals. This indicates that ADAMTS13 is complexed with immunoglobulin in these patients. The lack of ADAMTS13 expression in the plasma from patients with hereditary TTP may indicate defective synthesis, impaired cellular secretion, or enhanced degradation in the circulation. This study differentiated between normal and TTP plasma, as well as between congenital and acquired TTP. This method may, therefore, be used as a complement in the diagnosis of TTP.


A review of cutting-edge therapies for hepatocellular carcinoma (HCC): Perspectives from patents.
Rationale: Hepatocellular carcinoma (HCC) is a challenging disease due to its heterogenous etiology. Several breakthroughs have occurred in treatment of HCC, associated with an enormous number of patent publications for a variety of HCC treatment modalities. As patents can provide valuable information for academic research and commercial development, this study aims to unravel the cutting-edge therapies for HCC by using patents as an indicator. The outcome from this analysis may offer meaningful insights for respective policymaking, strategic plan and research and development (R&D) prioritization. Methods: Derwent Innovation platform was employed to collect the sample data of patents related to HCC treatment technologies worldwide as of December 31, 2019. Data inclusion, screening and exclusion were according to the rules of preferred reporting items for systematic reviews and meta-analyses (PRISMA). Technologies were classified based on Barcelona Clinic Liver Cancer (BCLC) staging system and recent clinical publications. Patent citation network analysis was carried out to identify and understand HCC therapeutic technology flow. Results: A dataset of 2543 patent documents and 528 patent families was generated. 11 technological categories were classified. Numerous researches were focalized on refinements in technologies and innovations within the field of HCC therapy, and the major achievements are technology advancement on molecular target therapy, chemotherapy, locoregional therapy, combination therapy and immunotherapy with demonstrated clinical benefits. In patent citation network, Notch pathway investigation, antibody drug conjugate (ADC) technology development and drug eluting beads trans artery chemoembolization (DEB-TACE) advancement are the major technological communities involving patents with the greatest future exploratory potential. Conclusion: Numerous emerging technologies have been identified in this study, in which exploring novel therapeutic targets in molecular target therapy, more localized and visible locoregional therapy and combination of immunotherapy with target therapy or other traditional therapies are highlighted as the future trends in treating HCC.


Reverse flow in the major infrarenal vessels--a capacitive phenomenon.
The arterial blood flow waveform is shown to change abruptly when passing from the thoracic aorta into the abdominal aorta in humans. Although this change has been accurately predicted by numerical solution of complicated pulse propagation equations, this paper demonstrates the ability of a simple lumped parameter model to explain this change in the waveforms using easily understood physical terms. The model correctly predicts changes in flow waveform under conditions of exercise and peripheral vascular disease. This analysis is useful in understanding abdominal artery physiology and explains the basis for clinical ultrasound Doppler examination of the legs.


The Welcome Baby Program: An Implementation and Outcomes Evaluation.
In 2015, First 5 LA contracted with the RAND Corporation to perform an implementation and outcomes evaluation of its Welcome Baby universal home visitation program. RAND designed and executed a mixed-methods implementation and outcomes evaluation program that examined program fidelity across 12 sites in Los Angeles County, each site's community referral and resource process, staff and participant experiences with the program, factors that may influence program attrition, short-term outcomes, and the relationship between program fidelity and outcomes. Data from multiple sources were used, including interviews with staff and focus groups with participants, quantitative data from staff and participant surveys, data collected by staff and entered into an administrative database, and document review. There was significant variation across the sites in meeting fidelity thresholds. Staff qualifications and training, reflective supervision, enrolling clients in the maternity ward, and service dosage elements were most challenging. Sites performed well in participant perceptions of their home visitor, supervisory requirements, and home visit content. Considerable variation in sites' community referral and resource process was also found. Welcome Baby participants achieved better outcomes compared to local and national benchmarks in more than half of the areas measured, including more positive parenting practices, higher levels of any breastfeeding, and safer sleep environments. Few clear patterns were evident in terms of relationships between meeting fidelity thresholds and outcomes. It is important to note challenges in evaluation, such as the lack of data to assess some of the fidelity and outcome domains.


Pelvic inflammatory disease in the adolescent: a poignant, perplexing, potentially preventable problem for patients and physicians.
The present review considers recent pelvic inflammatory disease literature. It remains a difficult condition to accurately diagnose and manage in the adolescent woman. Failure of accurate diagnosis and prompt management leads to complications, including chronic pelvic pain and infertility. Annual chlamydia screening of sexually active adolescents is an important method for early identification of this common cause of this disorder. Youth with positive screens can be lost for treatment if effective follow-up plans are not in place in clinical practice. The intrauterine device is not a risk factor for this condition in adolescents and is a recommended contraceptive device in sexually active adolescent women. A variety of chlamydial antigens are being used to help differentiate lower genital infection from upper genital disorder. Clinicians are not following established protocols for its diagnosis and management. Sequelae can be reduced in adolescent women if clinicians continue with regular chlamydia screening in sexually active adolescent women, have a low index of suspicion for pelvic inflammatory disease, carefully follow accepted treatment protocols, and teach youth comprehensive sexuality education including regular condom use. Funded research is needed to develop improved diagnosis and management tools as well as a chlamydia vaccine.


Naftifine cream in the treatment of cutaneous candidiasis.
Naftifine, a member of a new class of synthetic antifungal drugs, the allylamines, was evaluated for the treatment of cutaneous candidiasis. In a double-blind, parallel-group clinical trial, sixty patients with cutaneous candidiasis were randomly assigned to receive either naftifine cream 1 percent or its vehicle twice a day for three weeks. Two weeks after the end of therapy, 77 percent of the naftifine-treated patients were mycologically cured (negative results on potassium hydroxide preparations and culture) and had no clinically apparent disease, compared with 3 percent of the patients treated with vehicle (p less than 0.001). Side effects reported with naftifine cream were few and minor.


Coverage of Fertility Preservation and Treatment Among Surgical Trainees in the United States of America.
Surgery trainees spend their prime fertility years in training, which leads to delays in childbearing, accompanying infertility challenges, and high-risk pregnancies. Literature report of institutional support for fertility preservation (egg/sperm freezing) and treatment is lacking. The cost is particularly prohibitive while receiving a resident physician salary. This study aimed to assess availability of fertility resources and institutional coverage of fertility services to US General Surgery Residents (GSR) and Breast Fellows. We composed and distributed a 26-question survey to GS residency and fellowship program directors nationwide to survey residents and fellows. Summary and descriptive statistics were tabulated, and categorical variables were analyzed using Pearson's chi square test. A total of 234 US surgical trainees (male n = 75, female n = 155, unreported n = 4) completed the survey. Total of 12 % of trainees reported having been counseled on family planning/fertility treatment during training, and only 5.1% were counseled on fertility preservation. Perceived lack of support from program (p = 0.027) and counseling of fertility preservation (p = 0.009) were significantly associated with female gender. A minority (12.5%) reported having insurance coverage for fertility preservation and 26% had coverage of fertility treatment. In addition, 2.6% respondents pursued fertility preservation while in training and 33% reported they would pursue fertility preservation if it was covered by insurance. Fertility preservation is rarely discussed in US General Surgery residency programs. The large majority of GSR lacks awareness of insurance coverage of fertility preservation and treatment. Strong efforts are necessary to improve fertility education for GSR and insurance coverage to meet trainee's needs.


Perioperative supply chain management.
Faced with declining revenues and increasing operating expenses, hospitals are evaluating numerous mechanisms designed to reduce costs while simultaneously maintaining quality care. Many facilities have targeted initial cost reduction efforts in the reduction of labor expenses. Once labor expenses have been "right sized," facilities have continued to focus on service delivery improvements by the optimization of the "supply chain" process. This report presents a case study of the efforts of Vanderbilt University Medical Center in the redesign of its supply chain management process in the department of Perioperative Services. Utilizing a multidisciplinary project management structure, 3 work teams were established to complete the redesign process. To date, the project has reduced costs by $2.3 million and enhanced quality patient care by enhancing the delivery of appropriate clinical supplies during the perioperative experience.


Beaumont's contribution to gastric psychophysiology: a reappraisal.
William Beaumont's monograph on the physiology of digestion which was first published in 1833, has become a classic in its field. In a series of experiments over a 10 year period on Alexis St. Martin, a 19 year old Canadian voyageur with a traumatic gastric fistula, Beaumont was the first to describe many important aspects of the digestive process. In two of the 238 experiments Beaumont noted gastric physiological changes induced by emotional arousal, these being bile reflux and delayed gastric emptying. Elsewhere in the book, but not in experimental context, Beaumont referred to non-specific changes in coloration and secretion of the mucous membrane induced by emotion. Modern gastric psychophysiological research has shown that emotional arousal increases, and withdrawal decreases, gastric acid secretion. It has also been shown conclusively that emotion can cause a reflux of bile into the stomach and it may delay gastric emptying. Although the main thrust of Beaumont's work was physiological, he must be credited with being the first investigator to draw attention to the role of emotional arousal in the digestive process.


Peripheral Arterial Disease and Spinal Cord Injury: A Retrospective Nationwide Cohort Study.
The aim of this study was to elucidate the relationship between spinal cord injury (SCI) and the risk of peripheral arterial disease (PAD) in a cohort study with a large representative sample.The National Health Insurance Database was used to select patients who were diagnosed from 2000 to 2010. Patients with a history of PAD were excluded. The SCI group comprised 42,673 patients diagnosed with SCI, and we enrolled 170,389 matched controls (non-SCI group). We used a Cox proportional hazards regression model to analyze the adjusted risk of PAD between the case and control patients.Patients with SCI exhibited a significantly higher risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI] = 1.22-1.53) of PAD than patients without SCI. Patients with diabetes were at the highest risk of developing PAD (adjusted HR = 3.11, 95% CI = 2.80-3.44). Among patients without comorbidity, SCI patients exhibited a significantly higher risk of PAD than non-SCI patients. Furthermore, lumbar, sacral, or coccygeal spine, and multiple spine SCI were significantly associated with an increased risk of PAD (HR = 1.56, 95% CI = 1.33-1.84, HR = 2.11, 95% CI = 1.59-2.79, respectively).SCI is associated with an increased risk of PAD. Future studies should focus on modifying risk factors to reduce PAD risk among patients with SCI.


Effect of NaCl on leaf salt secretion and antioxidative enzyme level in roots of a mangrove, Aegiceras corniculatum.
Short-term salt (NaCl) treatment on Aegiceras corniculatum in roots and leaves showed no change in fresh and dry weight of leaves, roots and leaf area. There was no significant change in total soluble root protein, photosynthetic pigments of leaves and spectral characteristics of thylakoids. However, the activity of antioxidative enzymes (catalase, ascorbate peroxidase and guaiacol peroxidase) in roots decreased by 72, 58 and 80% respectively after 96 hr of treatment (300 mM of NaCl). Secretion of salts from the leaf salt glands and salt accumulation on upper surface of the leaves were quantified that revealed linear increase of salt secretion of leaf with increase in period of salt treatment. It was concluded that loss of activities of antioxidative enzymes at high salt treatment, caused leaf senescence in spite of high rates of salt secretion by Aegiceras corniculatum.


A Novel and Cost-Effective Method for Evaluating Cardiopulmonary Auscultation Skills in Student Physical Therapists.
Sophisticated high-fidelity human simulation (HFHS) manikins allow for practice of both evaluation and treatment techniques in a controlled environment in which real patients are not put at risk. However, due to high demand, access to HFHS by students has been very competitive and limited. In the present study, a basic CPR manikin with a speaker implanted in the chest cavity and internet access to a variety of heart and breath sounds was used. Students were evaluated on their ability to locate and identify auscultation sites and heart/breath sounds. A five-point Likert scale survey was administered to gain insight into student perceptions on the use of this simulation method. Our results demonstrated that 95% of students successfully identified the heart and breath sounds. Furthermore, survey results indicated that 75% of students agreed or strongly agreed that this manner of evaluation was an effective way to assess their auscultation skills. Based on performance and perception, we conclude that a simulation method as described in this paper is a viable and cost-effective means of evaluating auscultation competency in not only student physical therapists but across other health professions as well.


Category-Selectivity in Human Visual Cortex Follows Cortical Topology: A Grouped icEEG Study.
Neuroimaging studies suggest that category-selective regions in higher-order visual cortex are topologically organized around specific anatomical landmarks: the mid-fusiform sulcus (MFS) in the ventral temporal cortex (VTC) and lateral occipital sulcus (LOS) in the lateral occipital cortex (LOC). To derive precise structure-function maps from direct neural signals, we collected intracranial EEG (icEEG) recordings in a large human cohort (n = 26) undergoing implantation of subdural electrodes. A surface-based approach to grouped icEEG analysis was used to overcome challenges from sparse electrode coverage within subjects and variable cortical anatomy across subjects. The topology of category-selectivity in bilateral VTC and LOC was assessed for five classes of visual stimuli-faces, animate non-face (animals/body-parts), places, tools, and words-using correlational and linear mixed effects analyses. In the LOC, selectivity for living (faces and animate non-face) and non-living (places and tools) classes was arranged in a ventral-to-dorsal axis along the LOS. In the VTC, selectivity for living and non-living stimuli was arranged in a latero-medial axis along the MFS. Written word-selectivity was reliably localized to the intersection of the left MFS and the occipito-temporal sulcus. These findings provide direct electrophysiological evidence for topological information structuring of functional representations within higher-order visual cortex.