Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex.

BACKGROUND: Sex-related differences in colorectal (CRC) incidence and mortality are well-documented. However, the impact of sex on metabolic pathways that drive cancer growth is not well understood. High expression of asparagine synthetase (ASNS) is associated with inferior survival for female CRC patients only. Here, we used a CRISPR/Cas9 technology to generate HCT116 ASNS-/- and HCT 116 ASNS+/+ cancer cell lines. We examine the effects of ASNS deletion on tumor growth and the subsequent rewiring of metabolic pathways in male and female Rag2/IL2RG mice. RESULTS: ASNS loss reduces cancer burden in male and female tumor-bearing mice (40% reduction, q < 0.05), triggers metabolic reprogramming including gluconeogenesis, but confers a survival improvement (30 days median survival, q < 0.05) in female tumor-bearing mice alone. Transcriptomic analyses revealed upregulation of G-protein coupled estrogen receptor (GPER1) in tumors from male and female mice with HCT116 ASNS-/- xenograft. Estradiol activates GPER1 in vitro in the presence of ASNS and suppresses tumor growth. CONCLUSIONS: Our study indicates that inferior survival for female CRC patients with high ASNS may be due to metabolic reprogramming that sustains tumor growth. These findings have translational relevance as ASNS/GPER1 signaling could be a future therapeutic target to improve the survival of female CRC patients.

A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease.

PURPOSE OF REVIEW: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. RECENT FINDINGS: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

Neuroethics and neurolaw in forensic neuropsychiatry: A guide for clinicians.

As neuroscience technologies develop, ethical and legal questions arise regarding their use and societal impact. Neuroethics and neurolaw are growing interdisciplinary fields that address these questions. This review article presents the research agenda of both areas, examines the use and admissibility of neuroscience in expert testimony and legal settings, and discusses ethical issues related to forensic neuropsychiatrists claiming expertise in neuroscience, formulating medical opinions based on neuroscience, and considering its relevance to criminal responsibility. Forensic neuropsychiatrists should be aware of emerging neuroscientific evidence, its utility and limits in rendering diagnoses and explaining behavior, and, before seeking such evidence for legal purposes, its availability and admissibility. When testifying in matters involving neuroscientific evidence, ensuring truthfulness and balance, having sufficient and validated knowledge (including openness with confirming and disconfirming evidence), understanding standards of practice, and drawing relevant and appropriate conclusions remain important.

Engineered models of the lymphatic vascular system: Past, present, and future.

The lymphatic vascular system is crucial for optimizing body fluid level, regulating immune function, and transporting lipid. Relative to the experimental models to investigate blood vasculature, there are significantly fewer tools to explore lymphatics. Although in vivo studies have contributed to major discoveries in the field, finding and characterizing lymphatic specific markers has opened the door to isolating lymphatic vessels and cells for building ex vivo and in vitro platforms. These preparations have enabled the study and analysis of lymphatic vasculature in various physiological and pathophysiological conditions leading to a better understanding of cellular expressions and signaling. In this review, a broad range of ex vivo and in vitro engineered models are highlighted and categorized based on the major lymphatic function they model including contractile function, inflammation, drainage and immune regulation, lymphangiogenesis, and tumor-lymphatic interactions. Then, the novel 3D engineered tissues are introduced consisting of acellularized scaffolds and hydrogels to form vessels and cellular structures close to in vivo morphology. This paper also compares traditional in vitro methods with recent technologies and elaborates on the inherent advantages and limitations of each preparation by critically discussing simplest to most complex tissue-cellular structures. It concludes with an outlook of the lymphatic vasculature models and the possible future direction of contemporary tools, such as organ-on-chips.

Assessment of Lactobacillus rhamnosus mediated protection against arsenic-induced toxicity in zebrafish: a qPCR-based analysis of Firmicutes and Bacteroidetes groups and embryonic development.

Arsenic poses a significant health risk worldwide, impacting the gut microbiota, reproductive health, and development. To address this issue, a cost-effective method like probiotic supplementation could be beneficial. However, the interplay between arsenic toxicity, probiotics, gut microbiota, and maternal transcript modulation remains unexplored. This study investigates the impact of Lactobacillus rhamnosus (L. rhamnosus) DSM 20021 on the proportions of Firmicutes and Bacteroidetes, as well as its effects on embryonic development in zebrafish induced by arsenic trioxide (As2O3). Adult zebrafish were exposed to both high and environmentally relevant concentrations of As2O3 (10, 50, and 500 ppb) for 1, 6, and 12 weeks. qPCR analysis revealed increased proportions of Firmicutes and Bacteroidetes in all As2O3-exposed and As2O3 + L. rhamnosus-exposed groups, while no significant changes were observed in groups exposed only to L. rhamnosus DSM 20021. The larvae, exposed to 500 ppb of As2O3 for 12 weeks, exhibited low growth, decreased survival rates, and morphological deformities. However, these adverse effects were reversed upon exposure to only L. rhamnosus DSM 20021. Furthermore, the expression of DVR1 and ABCC5, which are involved in defense against xenobiotics and embryo development, decreased significantly in As2O3 (500 ppb) and As2O3 (500 ppb) + L. rhamnosus-exposed groups, whereas ameliorative effects were observed in only L. rhamnosus DSM 20021-exposed groups.

The prospects of microphysiological systems in modeling platelet pathophysiology in cancer.

The contribution of platelets is well recognized in thrombosis and hemostasis. However, platelets also promote tumor progression and metastasis through their crosstalk with various cells of the tumor microenvironment (TME). For example, several cancer models continue to show that platelet functions are readily altered by cancer cells upon activation leading to the formation of platelet-tumor aggregates, triggering release of soluble factors from platelet granules and altering platelet turnover. Further, activated platelets protect tumor cells from shear forces in circulation and assault of cytotoxic natural killer (NK) cells. Platelet-secreted factors promote proliferation of malignant cells, metastasis, and chemoresistance. Much of our knowledge of platelet biology in cancer has been achieved with animal models, particularly murine. However, this preclinical understanding of the complex pathophysiology is yet to be fully realized and translated to clinical trials in terms of new approaches to treat cancer via controlling the platelet function. In this review, we summarize the current state of knowledge of platelet physiology obtained through existing in vivo and in vitro cancer models, the complex interactions of platelets with cancer cells in TME and the pathways by which platelets may confer chemoresistance. Since the FDA Modernization Act recently passed by the US government has made animal models optional in drug approvals, we critically examine the existing and futuristic value of employing bioengineered microphysiological systems and organ-chips to understand the mechanistic role of platelets in cancer metastasis and exploring novel therapeutic targets for cancer prevention and treatment.

The recent passage of the FDA Modernization Act by the US government has removed the requirement of the use of animal models in disease modeling and drug discovery process. This has resulted in a much-renewed excitement within engineers, scientists, and industry in applying in vitro cell biosystems as a platform technology that assists or replaces animals in reproducing human biology. The contribution of platelets is well recognized in thrombosis and hemostasis. However, platelets also promote tumor progression and metastasis through their crosstalk with various cells of the tumor microenvironment. In this review, we summarize the current state of knowledge of platelet physiology obtained through existing cancer models and also critically examine the existing and futuristic value of employing bioengineered organ-chips to improve the knowledge of the underlying biology.

Intracellular calcium dynamics of lymphatic endothelial and muscle cells co-cultured in a Lymphangion-Chip under pulsatile flow.

The lymphatic vascular function is regulated by pulsatile shear stresses through signaling mediated by intracellular calcium [Ca2+]i. Further, the intracellular calcium dynamics mediates signaling between lymphatic endothelial cells (LECs) and muscle cells (LMCs), including the lymphatic tone and contractility. Although calcium signaling has been characterized on LEC monolayers under uniform or step changes in shear stress, these dynamics have not been revealed in LMCs under physiologically-relevant co-culture conditions with LECs or under pulsatile flow. In this study, a cylindrical organ-on-chip platform of the lymphatic vessel (Lymphangion-Chip) consisting of a lumen formed with axially-aligned LECs co-cultured with transversally wrapped layers of LMCs was exposed to step changes or pulsatile shear stress, as often experienced in vivo physiologically or pathologically. Through real-time analysis of intracellular calcium [Ca2+]i release, the device reveals the pulsatile shear-dependent biological coupling between LECs and LMCs. Upon step shear, both cell types undergo a relatively rapid rise in [Ca2+]i followed by a gradual decay. Importantly, under pulsatile flow, analysis of the calcium signal also reveals a secondary sinusoid within the LECs and LMCs that is very close to the flow frequency. Finally, LMCs directly influence the LEC calcium dynamics both under step changes in shear and under pulsatile flow, demonstrating a coupling of LEC-LMC signaling. In conclusion, the Lymphangion-Chip is able to illustrate that intracellular calcium [Ca2+]i in lymphatic vascular cells is dependent on pulsatile shear rate and therefore, serves as an analytical biomarker of mechanotransduction within LECs and LMCs, and functional consequences.

SLAP Injury and the Superior Labrum.

Injuries around the superior labrum are a common cause of shoulder dysfunction and pain. The injuries sustained result mainly from repetitive microtrauma but can also occur following a fall on outstretched hand. Both athletic and general populations can be affected. Injuries to the superior labrum are called superior labrum anterior and posterior (SLAP) tears. Based on cross-sectional imaging findings, the literature defines four main SLAP tears (I-IV) and six extended types (V-X). An accurate description of imaging findings of the SLAP tear type, along with concomitant findings, aids clinicians in treatment planning. We also briefly discuss management options, postoperative appearance of superior labral repair, and the diagnosis of a retear.

Gender-Affirming Surgeries: A National Surgical Quality Improvement Project Database Analyzing Demographics, Trends, and Outcomes.

BACKGROUND: Gender affirmation surgery is an exponentially growing field within plastic surgery. The aim of our study is to analyze demographics, procedure type, trends, and outcomes in the surgical management of gender identity disorder in the past few years. METHODS: The American College of Surgeons NSQIP database was queried for the years 2015 to 2019. International Classification of Diseases codes were used to identify all gender-affirming cases. Patients were categorized by procedure type using Current Procedural Terminology codes for feminizing/masculinizing top, bottom and head/neck procedures. Patient demographics, comorbidities, and postoperative complications were analyzed using SPSS statistics software. A comparative analysis was performed among the procedure type. RESULTS: From 2015 to 2019, 4114 patients underwent a gender-affirming surgery (GAS) increasing the number of surgeries by over 400%, according to the NSQIP database. Demographics include age (mean = 32 years), body mass index (mean = 28 kg/m2), race (60% White, 22% unknown, 13% African American, 4% Asian, 1% other). Female to male procedures represented the most commonly performed (n = 2647; 64%), followed by male to female (n = 1278; 31%) with head/neck procedures representing 5% (n = 189) of all procedures. Top surgeries were also the most common (n = 2347, 57%), followed by bottom surgeries (n = 1578, 38%). The overall complication rate was 6% (n = 247), 2.1% (n = 4) for head/neck procedures, 8% (n = 134) for bottom procedures, and 3.5% (n = 84) for top surgeries.A reoperation within 30 days and related to the initial GAS occurred for 52 patients. Postoperative complication rates were statistically different between bottom surgeries compared with the top and head/neck procedure groups (P < 0.001). Increasing age and body mass index showed a significantly higher odds of having a complication. CONCLUSIONS: Gender-affirming procedures have significantly increased over the past 5 years. Increased exposure through literature and research, as well as an improvement in social climates, including increasing insurance coverage have contributed to the expansion of these procedures. Low serious complication rates within 30 days prove GAS to be safe.

A Comparison of Applicant and Resident Physician Demographics Among Surgical Subspecialties From 2009 to 2019: Trends in Gender and Underrepresented Minorities in Medicine.

BACKGROUND: The purposes of this study were to compare applicant statistics to resident physician demographics among several surgical subspecialties (SSSs), to identify trends of gender and underrepresented minorities in medicine (UIM), and to evaluate current diversity among these specialties. METHODS: Graduate medical education reports from 2009 to 2019 were queried to determine trends among programs. Further identification of gender and UIM statistics was obtained in 4 several SSSs: integrated plastic surgery, orthopedic surgery (OS), otolaryngology surgery (ENT), and neurosurgery (NS). These were compared with Association of American Medical Colleges data of residency applicants for the respective years. RESULTS: Significant differences were seen among gender and UIM(s) of the applicant pool when compared with resident data. All specialties had significantly fewer American Indian and African American residents compared with applicants. Significant differences between applicants and residents were also found among Hispanic, Native Hawaiian, and female demographics. All SSSs had a significant positive trend for the percentage of female residents. Significant differences between specialties were identified among African American, Hispanic, and female residents. Orthopedic surgery and NS had significantly higher percentage of African American residents compared with ENT and integrated plastic surgery. Neurosurgery had significantly higher percentage of Hispanic residents compared with OS and ENT. Integrated plastic surgery and ENT had significantly higher percentage of female residents compared with OS and NS. CONCLUSIONS: There has been significant increase in number of residency programs and resident positions since 2009. However, increase in female residents and UIM(s) among SSSs has not matched the pace of growth.

Engineering new microvascular networks on-chip: ingredients, assembly, and best practices.

Tissue engineered grafts show great potential as regenerative implants for diseased or injured tissues within the human body. However, these grafts suffer from poor nutrient perfusion and waste transport, thus decreasing their viability post-transplantation. Graft vascularization is therefore a major area of focus within tissue engineering because biologically relevant conduits for nutrient and oxygen perfusion can improve viability post-implantation. Many researchers utilize microphysiological systems as testing platforms for potential grafts due to an ability to integrate vascular networks as well as biological characteristics such as fluid perfusion, 3D architecture, compartmentalization of tissue-specific materials, and biophysical and biochemical cues. While many methods of vascularizing these systems exist, microvascular self-assembly has great potential for bench-to-clinic translation as it relies on naturally occurring physiological events. In this review, we highlight the past decade of literature and critically discuss the most important and tunable components yielding a self-assembled vascular network on chip: endothelial cell source, tissue-specific supporting cells, biomaterial scaffolds, biochemical cues, and biophysical forces. This article discusses the bioengineered systems of angiogenesis, vasculogenesis, and lymphangiogenesis, and includes a brief overview of multicellular systems. We conclude with future avenues of research to guide the next generation of vascularized microfluidic models and future tissue engineered grafts.

Log ODDS (LODDS) of positive lymph nodes as a predictor of overall survival in squamous cell carcinoma of the penis.

OBJECTIVE: To evaluate the role of logarithmic ODDS (LODDS) in the number of positive lymph nodes and the number of negative lymph nodes as a prognostic metric in the squamous cell carcinoma (SCC) penis. METHODS: Data were retrospectively collected from 96 cases of SCC penis that underwent bilateral groin dissection between 2010 and 2015 at our institute. Lymph node density (LND) and LODDS were calculated for all the patients and classified according to American Joint Committee on Cancer (AJCC) pN staging. Thresholds for LND (24% and 46%) and LODDS (-0.75 and 0) were established. Multivariate analysis of various cofactors was done with overall survival (OS) as a dependent factor. Three classification systems were compared using receiver operative characteristic (ROC) curve analysis. RESULTS: Univariate analysis showed that AJCC pN, LND, and LODDS were all significantly correlated with OS. However, only LODDS (HR, 11.185; p = .023) remained an independent prognostic factor through multivariate analysis. LODDS (log-likelihood = 3832 vs. 3798; p < .001) had better prognostic performance than pN and better discriminatory ability than LND (AIC = 3902 vs. 3928). LODDS had better power of discrimination than LND and pN. LODDS could predict survival in lymph node yield (LNY) < 15 (p < .001). CONCLUSION: LODDS is an independent predictor of OS in the SCC penis and has superior prognostic significance than the AJCC pN and LND classification systems.

PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury.

Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gßγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB-mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling.

Cost Analysis and National Trends in the Treatment of Thumb Basal Arthritis: Comparing Ligament Reconstruction/Tendon Interposition and Trapeziectomy/Hematoma Distraction Arthroplasty.

BACKGROUND: Thumb basal arthritis (TBA) is a common form of arthritis characterized by wearing away of cartilage in the crarpometacarpal joint at the base of the thumb. The purpose of the study was to analyze cost trends of the 2 common surgical treatments options: ligament reconstruction/tendon interposition (LRTI) and trapeziectomy/hematoma distraction arthroplasty (THDA). METHODS: The Vizient Clinical Data/Resource Manager electronic database was reviewed for the 3 treatment procedures of TBA from January 1, 2016, to December 31, 2019. Cases were placed into 1 of 2 categories: LRTI or THDA. Total and direct costs were averaged and compared nationally and regionally. One-tailed t test and Pearson correlation analyses were performed (P < 0.05 and r > 0.9 or r < -0.9 was considered significant). RESULTS: A total of 28,887 total cases (26,405 LRTI, 2482 THDA) were analyzed. There was a 49% increase in number of surgical procedures to treat TBA between 2015 and 2018. Ligament reconstruction/tendon interposition (91%) had larger market share than THDA (9%). However, market share percentage of each procedure stayed the same over time. Trapeziectomy/hematoma distraction arthroplasty had lower average cost (US $4157) compared with that of LRTI (US $4446, P = 0.06) However, THDA had a significant positive trend in cost, increasing 14% in 4 years. In 2019, 30% of procedures performed were in the Midwestern United States, 27% Northeastern United States, 24% Southern United States, and 19% Western United States. CONCLUSIONS: Most patients with TBA seem to be treated with LRTI. The market share seems to be greatest for LRTI and lowest for THDA nationally and regionally. Although the average cost for THDA was less than that of LRTI, this difference was not significant.

Cost Analysis and National Trends in the Treatment of Dupuytren Contracture Comparing Collagenase Injection, Needle Fasciotomy, and Open Fasciectomy Procedures.

BACKGROUND: Dupuytren contracture (DC) is a common disorder characterized by progressive fibrosis of palmar fascia. This study analyzed cost trends of 3 common treatments for DC: fasciotomy, fasciectomy, and collagenase injection (CI)/cord manipulation. METHODS: The Vizient Clinical Data/Resource Manager electronic database was reviewed for all procedures for the treatment of DC at participating hospitals in the United States (US) from October 1, 2015, to September 1, 2019. Cases were placed into 1 of 3 categories: (1) CI, (2) needle fasciotomy (NF), and (3) open fasciectomy (OF). Total and direct costs were averaged for each procedure and compared nationally and regionally. Temporal trends and specific market share were analyzed. One-tailed t test and Pearson correlation analysis was performed (P < 0.05 and r > 0.9 or r < -0.9 was considered significant). RESULTS: A total of 22,974 total cases were identified. A total of 16,966 OF, 3962 NF, and 2046 CI were performed. There was a nearly a 4-fold increase in number of procedures to treat DC from 2015 to 2018. Market share percentage of each procedure stayed relatively similar over time. However, market share percentage differed between procedures. Needle fasciotomy had the lowest market share percentage approximately 7%. Collagenase injection had the highest average cost at US $4453.66 and was significantly higher than OF at US $3394.90 and NF at US $2010.75. Cost and distribution of procedures were further analyzed by geographic regions. In 2018, 32% of procedures performed were in the Northeastern US, 29% in the Midwestern US, 23% in the Southern US, and 16% in the Western US. Total number of Dupuytren procedures increased more than 300% in all regions across the US from 2015 to 2018. In every region, NF was the lowest cost intervention. Cost of OF and CI varied between regions and was often the most expensive intervention. CONCLUSIONS: Treatment of DCs with NF seems to be the least costly treatment option. Needle fasciotomy seems to be the least commonly performed procedure. Regional data show variations in the cost of OF and CI. However, OF has the majority market share nationally and regionally. Although the cost of these procedures seems to vary regionally, the type of procedures being performed seem to be similar across regions.

Cholera outbreak in an informal settlement at Shahpur huts, Panchkula District, Haryana State, India, 2019.

In September 2019, after a reported death due to acute diarrheal disease in Shahpur village, Panchkula district, Haryana state, India, we conducted an outbreak investigation to identify the etiological agent, estimate the burden of disease, and make recommendations to prevent future outbreaks. The suspected cholera case was a resident of Shahpur huts, ≥1 year of age having ≥3 loose stools within a 24-h period between September 1 and 28, 2019 and a laboratory-confirmed cholera case, whose stool specimen tested positive for Vibrio cholerae. We identified 196 suspected cholera cases with a median age of 18 years (range: 1-65 years); 54% (106) being female. The overall attack rate was 8% (196/2,602), and the case fatality rate was 1% (2/196). Tested samples of water from tanks (n = 6), sewage effluent (n = 2), and 22% (4/18) of stool specimens collected from suspected cases were positive for V. cholerae. Strengthening surveillance, improving water, and sanitation systems are recommended to prevent future cholera outbreaks.

Microengineered Human Vein-Chip Recreates Venous Valve Architecture and Its Contribution to Thrombosis.

Deep vein thrombosis (DVT) and its consequences are lethal, but current models cannot completely dissect its determinants-endothelium, flow, and blood constituents-together called Virchow's triad. Most models for studying DVT forego assessment of venous valves that serve as the primary sites of DVT formation. Therefore, the knowledge of DVT formed at the venous cusps has remained obscure due to lack of experimental models. Here, organ-on-chip methodology is leveraged to create a Vein-Chip platform integrating fully vascularized venous valves and its hemodynamic, as seen in vivo. These Vein-Chips reveal that vascular endothelium of valve cusps adapts to the locally disturbed microenvironment by expressing a different phenotype from the regions of uniform flow. This spatial adaptation of endothelial function recreated on the in vitro Vein-Chip platform is shown to protect the vein from thrombosis from disturbed flow in valves, but interestingly, cytokine stimulation reverses the effect and switches the valve endothelium to becoming prothrombotic. The platform eventually modulates the three factors of Virchow's triad and provides a systematic approach to investigate the determinants of fibrin and platelet dynamics of DVT. Therefore, this Vein-Chip offers a new preclinical approach to study venous pathophysiology and show effects of antithrombotic drug treatment.

Aetiology and outcome of acute diarrhoea in children with severe acute malnutrition: a comparative study.

OBJECTIVE: To compare the microbiological profile, clinical course and outcome of acute diarrhoea in children aged <5 years having severe acute malnutrition (SAM) with those of children having normal nutritional status. DESIGN: Cross-sectional comparative study. SETTING: Tertiary-care hospital catering mainly to the urban poor of East Delhi, India. PARTICIPANTS: Children aged <5 years (n 140; seventy with SAM (cases) and seventy with normal anthropometry (controls)) with acute diarrhoea (duration < 14 d). Stool samples were collected for conventional culture, microscopy, acid-fast staining, rotavirus and Cryptosporidium antigen detection, and subtyping of diarrhoeagenic Escherichia coli (DEC). We followed-up these children for persistent diarrhoea and subsequent diarrhoeal episode in the next 3 months. RESULTS: Rotavirus was detected in six (9 %) cases and in fifteen (21 %) controls (P = 0·03; OR = 0·34; 95 % CI 0·12, 0·94). DEC was isolated significantly more in cases compared with controls (93 v. 64 %; P < 0·001; OR = 7·25; 95 % CI 2·57, 20·4). Cryptosporidium was detected in seven (10 %) cases and five (7 %) controls. Total duration of diarrhoea and percentage change in weight after resolution of diarrhoea were comparable between cases and controls. At 3-month follow-up, number of subsequent episodes of diarrhoea and persistent diarrhoea were comparable between the two groups. CONCLUSIONS: Rotavirus was found significantly less frequently, whereas DEC was detected more frequently in children with SAM in comparison to non-malnourished children. To further reduce diarrhoea-related mortality, preventive and therapeutic interventions need to be designed against organisms causing diarrhoea in children with SAM.

Hand Surgery Referral Pattern Preferences Among Primary Care Physicians in Academic Centers in the Southeastern United States.

BACKGROUND: Board-certified hand surgeons undergo an additional 1 year of fellowship training after completing 1 of 3 residencies, either orthopedic surgery (OS), plastic surgery (PS), or general surgery (GS). The purpose of our study was to examine primary care physician's referral patterns for hand surgery in the Southeastern United States. METHODS: Primary care physicians across 38 academic medical institutions in the Southeastern United States were queried. A survey questionnaire was sent to their corresponding email address. The Questionnaire allowed the surveyor to enter demographic information and their choice in referral, either to OS, PS, or GS, for each particular hand pathology. RESULTS: Two-hundred twenty-eight of 1526 surveys were completed (15% response rate). One-hundred twenty-four were male respondents, and 105 were female. For treatment of arthritis, 94.7% selected OS; 5.3%, PS; and 0%, GS. For treatment of nerve decompression, 84.0% selected OS; 14.4%, PS; and 1.6%, GS. For treatment of nerve injuries, 64.2% selected OS; 34.6%, PS; and 1.2%, GS. For treatment of tendon injuries, 84.4% selected OS; 15.6%, PS; and 0%, GS. For treatment of congenital deformities, 55.1% selected OS; 44.9%, PS; and 0%, GS. For treatment of fractures, 98.8% selected OS; 1.2%, PS; and 0%, GS. For treatment of sports-related injuries, 99.2% selected OS; 0.4%, PS; and 0.4%, GS. For treatment of soft tissue masses, 65.5% selected OS; 23.0%, PS; and 11.5%, GS. For treatment of soft tissue coverage, 8.6% selected OS; 87.7%, PS; and 3.7%, GS. For treatment of skin cancer-related problems, 8.2% selected OS; 72.4%, PS; and 19.4%, GS. CONCLUSIONS: Referrals for arthritis, nerve decompressions, tendon injuries, fractures, and sports injuries are more likely to be referred to OS. Referrals for soft tissue coverage and skin cancers are more likely to be referred to PS. Nerve injuries and congenital deformities referrals were similar between orthopedic and PS. Further research should be conducted to determine why referral patterns vary among specialties with similarly trained hand surgeons.

Cholinesterase inhibition and its association with hematological, biochemical and oxidative stress markers in chronic pesticide exposed agriculture workers.

The present study investigated the pesticide induced adverse health effects, hematological and biochemical alterations among agriculture workers. A cross sectional study of 51 agriculture workers and 54 unexposed subjects was carried out to evaluate hematological and biochemical alterations in blood. Pesticide exposed individuals were reported adverse clinical outcomes, including tingling, muscle pain, headache, skin disease, etc. A significant alterations in the level of hematological parameters, liver and renal dysfunctions markers and lipid profile suggested hematological, hepatic and renal dysfunctions. A significant decrease in the activity of acetylcholinesterase, reduced glutathione, superoxide dismutase, catalase and increased level of lipid peroxidation was also observed in these agriculture workers. Correlation coefficient analysis showed a positive correlation of chronic exposure with most of the hematological and biochemical parameters. The results demonstrate that the chronic exposure of pesticides cause reduction in the acetylcholinesterase activity and enhanced the risk of adverse clinical outcomes in agriculture workers.