Research Capacity for Prevention and Control of Non-communicable Diseases and their Risk Factors in Nepal: Findings of a Needs Assessment Study.

Background Despite a high burden, there are limited trainings in non-communicable disease research in Nepal. Objective We conducted a needs assessment to assess existing research training capacity in academic health institutions of Nepal for the prevention and control of noncommunicable diseases, identify gaps in research, and explore the feasibility of developing research training program in Nepal targeting non-communicable diseases. Method We did mixed-method research and reviewed academic institution curricula and scientific articles authored by Nepali researchers. We conducted 14 Focus Group Discussions with bachelor and masters level students of public health and community medicine; 25 In-depth Interviews with department heads and faculties, and government stakeholders. We surveyed medical and public health students on their research knowledge and skills development. Result Research methodology component was addressed differently across academic programs. One-third (33.7%) of students expressed lack of skills for analysis and interpretation of data. They felt that there is a wide scope and career-interest in non-communicable diseases research in Nepal. However, specific objectives in the curriculum and practical aspects regarding non-communicable diseases were lacking. Most of the non-communicable diseases research in Nepal are prevalence studies. Lack of funding, conflicting priorities with curative services, and inadequate training for advanced research tools were reported as major barriers. Conclusion Nepal must strengthen the whole spectrum of research capacity: epidemiological skills, research management, and fund development. Generation of a critical mass of non-communicable disease researchers must go together with improved funding from the government, non-governmental, and external funding organizations.

A National Equity Initiative to Address Noncommunicable Diseases and Injuries: Findings and Recommendation from the Nepal NCDI Poverty Commission.

We aimed to assess the burden of NCDIs across socioeconomic groups, their economic impact, existing health service readiness and availability, current policy frameworks and national investment, and planned programmatic initiatives in Nepal through a comprehensive literature review. Secondary data from Global Burden of Disease estimates from GBD 2015 and National Living Standard Survey 2011 were used to estimate the burden of NCDI and present the relationship of NCDI burden with socioeconomic status. The Commission used these data to define priority NCDI conditions and recommend potential cost-effective, poverty-averting, and equity-promoting health system interventions. NCDIs disproportionately affect the health and well-being of poorer populations in Nepal and cause significant impoverishment. The Commission found a high diversity of NCDIs in Nepal, with approximately 60% of the morbidity and mortality caused by NCDIs without primary quantified behavioral or metabolic risk factors, and nearly half of all NCDI-related DALYs occurring in Nepalese younger than 40 years. The Commission prioritized an expanded set of twenty-five NCDI conditions and recommended introduction or scale-up of twenty-three evidence-based health sector interventions. Implementation of these interventions would avert an estimated 9680 premature deaths per annum by 2030 and would cost approximately $8.76 per capita. The Commission modelled potential financing mechanisms, including increased excise taxation on tobacco, alcohol, and sugar-sweetened beverages, which would provide significant revenue for NCDI-related expenditures. Overall, the Commission's conclusions are expected to be a valuable contribution to equitable NCDI planning in Nepal and similar resource-constrained settings globally.

Neonatal testing leading to the identification of Bh (para-Bombay) phenotype in the mother: case report with review of the literature.

Para-Bombay is a rare phenotype with a homozygous nonfunctional FUT1 gene and a normal FUT2 gene leading to H-deficient red blood cells (RBCs) with or without ABH substances, depending on inheritance of the ABO gene. This case is about a 5-day-old male baby suffering from sepsis who required a 45-mL packed RBC transfusion. The baby's sample tested as A1B, D+ and mother's sample tested as group O, D+ with group 4 discrepancy due to ABO isoagglutinins. Further workup of the mother's sample with anti-H lectin was negative, which suggested the mother to be group Oh, D+. Antibody screening was panreactive with negative autocontrol, suggestive of anti-H. The titer of immunoglobulin (Ig)M anti-H was 64, IgG titer using dithiothreitol was 8, and anti-IH was absent. A negative adsorption and elution test suggested that RBCs were devoid of A and B antigens. The father's sample tested clearly as group A1, D+; hence, the cis-AB blood group was ruled out in the baby. The secretor study of the mother's saliva revealed the presence of B and H substances that neutralized polyclonal B and H antisera. Therefore, we concluded that the mother was of the para-Bombay (Bh) phenotype. This case highlights the importance of reverse grouping and resolving blood grouping discrepancies between mother and child-in this case because of an incongruous ABO blood type of the baby and the mother who was previously tested as group O, D+.Para-Bombay is a rare phenotype with a homozygous nonfunctional FUT1 gene and a normal FUT2 gene leading to H-deficient red blood cells (RBCs) with or without ABH substances, depending on inheritance of the ABO gene. This case is about a 5-day-old male baby suffering from sepsis who required a 45-mL packed RBC transfusion. The baby's sample tested as A1B, D+ and mother's sample tested as group O, D+ with group 4 discrepancy due to ABO isoagglutinins. Further workup of the mother's sample with anti-H lectin was negative, which suggested the mother to be group Oh, D+. Antibody screening was panreactive with negative autocontrol, suggestive of anti-H. The titer of immunoglobulin (Ig)M anti-H was 64, IgG titer using dithiothreitol was 8, and anti-IH was absent. A negative adsorption and elution test suggested that RBCs were devoid of A and B antigens. The father's sample tested clearly as group A1, D+; hence, the cis-AB blood group was ruled out in the baby. The secretor study of the mother's saliva revealed the presence of B and H substances that neutralized polyclonal B and H antisera. Therefore, we concluded that the mother was of the para-Bombay (Bh) phenotype. This case highlights the importance of reverse grouping and resolving blood grouping discrepancies between mother and child­in this case because of an incongruous ABO blood type of the baby and the mother who was previously tested as group O, D+.

A Network Thermodynamic Analysis of Amyloid Aggregation along Competing Pathways.

Aggregation of proteins towards amyloid formation is a significant event in many neurodegenerative diseases. Low-molecular weight oligomers are considered to be the primary toxic agents in many of these maladies. Therefore, there is an increasing interest in understanding their formation and behavior. In this paper, we build on our previously established theoretical investigations on the interactions between Aß and lipids (L) that adopt off-pathway fibril formation under the control of L concentrations. Our previously developed competing game theoretic framework between the on- and off-pathway dynamics has been expanded to understand the underlying network topological structures in the reaction kinetics of amyloid formation. The mass-action based dynamical systems are solved to identify dominant pathways in the system with fixed initial conditions, and variations in the occurrence of these dominant pathways are identified as a function of various seeding conditions. The mechanistic approach is supported by thermodynamic free energy computations which helps identify stable reactions. The resulting analysis provides possible intervention strategies that can draw the dynamics away from the off-pathways and potential toxic intermediates. We also draw upon the classic literature on network thermodynamics to suggest new approaches to better understand such complex systems.

Assessment of Health Service Delivery to Address Cardiovascular Diseases in Nepal.

Background A health care delivery system is the organization of people, institutions, and resources designed to deliver health services. A comprehensive study to explore cardiovascular health service delivery in Nepal is lacking. Objective This study attempted to assess Nepal's health system gap on organization and delivery of cardiovascular disease prevention and management services. Method This mixed-method study used the six building blocks of the World Health Organization health system framework: organization; access; coverage, utilization and demand; equity; quality of services; and outcomes. We conducted the desk reviews of national and international documents, performed several key informant interviews, calculated the relevant indicators, and assessed the Strengths, Weaknesses, Opportunities, and Threats of the cardiovascular health service delivery. Result We found that most of the cardiovascular services are concentrated in urban areas, and suffer from poor access, quality, utilization, and coverage in most of the areas resulting in poor health outcomes. Though the services have recently improved due to increased primary care interventions, there is scope for the development of competent human resources, advancement of technologies, development of national protocols, and improved monitoring and supervision. Improved disease system including the medical recording and reporting mechanism to incorporate and reflect the true burden of CVD in Nepal is lacking. Conclusion Despite having health facilities from grassroots to the central level, availability, access, and quality of cardiovascular health services are poor. Further improvement and equitable expansion of promotive, preventive, diagnostic, referral, and rehabilitative cardiovascular services are needed to ensure universal health coverage.

Determination and Evaluation of Sense of Coherence in Women in Semi-urban Nepal: A part of the Heart-health Associated Research, Dissemination, and Intervention in the Community (HARDIC) Trial.

Background Sense of coherence (SOC) is a core concept of salutogenesis which relates to individuals' overall life orientation. Stronger SOC associates with better coping strategies, better health, and better quality of life. Although the SOC-questionnaire is validated in many cultures and languages, it has not, to date, been applied in Nepal. Objective To determine and evaluate women's SOC before and after a health education intervention. Method This study was conducted as a part of the Heart-health Associated Research, Dissemination, and Intervention in the Community in the semi-urban JhaukhelDuwakot Health Demographic Surveillance Site in Nepal. Jhaukhel and Duwakot were selected as the control and intervention areas, respectively. Participants were women with children aged 1-7 years. Eight hundred and fifty-seven women before and 1,268 women after the health education intervention participated in the study. The statistical analysis was carried out with chi-square tests and one-way uni-variate ANOVA. Result Women's total SOC mean values at baseline were 51.1-57.4 and at follow up 54.4-54.9 in the intervention and control area, respectively. At baseline, SOC was significantly weaker in the intervention area compared to the control area (p < 0.001). At followup three months later, SOC was significantly stronger in the intervention area than in the control area (p < 0.001). Conclusion Nepalese women had weaker SOC than women in high-income countries, but comparable to neighboring country India with similar cultural features. Empowerment of women through community participation and health education strengthened SOC. The SOC-13-questionnaire in its Nepali version is recommended to be further evaluated.

Kinetic evaluation for rapid degradation of dimethylamine enriched with Agromyces and Ochrobactrum sp.

Dimethylamine (DMA) possesses an obnoxious odor which has resulted in public concern during the past several decades. A rare bacterial species proficient to degrade DMA, designated IR-26, was isolated from Indian Oil Corporation Limited (IOCL) and identified as Agromyces and Ochrobactrum sp., which has presented a rapid degradation when compared to other bacterial species which were capable to degrade DMA. The removal efficiency of 100% has been calculated in different concentration of DMA. The kinetic study reveals the maximum reduction rate of DMA was 0.11 per hour and the maximum growth rate of biomass was 0.013 per hour respectively. The saturation constant of DMA was around 1.96 mg/L which shows a high affinity of DMA. The importance of these analyses is offered and conversed in this paper.

Environmental quality monitoring and impact assessment of solid waste dumpsites in high altitude sub-tropical regions.

Solid Waste Management (SWM) in high altitude regions is critically phased because of the non-availability of suitable facilities for the treatment and handling of large quantities of Municipal Solid Waste (MSW). Open burning practices at hill slopes were noticed which affect the surrounding environment. Hence, it became essential to measure the environmental components around the dumpsites to examine the impacts and suggest new technological solutions. The pollution parameters were monitored in and around the dumpsites, and the data was analysed using statistical tools. The assessment of air quality indicated maximum fine suspended particulate matter (PM2.5) concentration of 206.66 µg/m3 followed by respairable particulate matter (PM10), oxides of nitrogen (NOx) and sulphur dioxide (SO2). Among the gaseous emissions, methane (CH4) concentration was very high (38.53 mg/L) followed by carbon monoxide (CO) concentration (0.96 mg/L). Volatile organic compounds (VOCs) were also detected at few dumpsites with highest observed benzene (C6H6) concentration of 157.53 µg/m3. The soil sample analysis indicated that iron (Fe) concentration dominates followed by manganese (Mn), zinc (Zn), chromium (Cr), copper (Cu), and nickel (Ni). For evaluation of different alternatives for the SWM system, Rapid Impact Assessment Matrix (RIAM) was applied.

A longitudinal study of altered taste and smell perception and change in blood pressure.

BACKGROUND AND AIMS: Previous studies suggest that olfactory receptors, which mediate smell chemosensation, are located in the kidney and involved in blood pressure regulation. Mammalian epithelial sodium channels located in taste receptor cells are also found to participate in blood pressure regulation. However, there is currently no human study that has examined the association between taste and smell function and blood pressure. We thus conducted a longitudinal study to examine whether participants with altered taste and smell perception had larger increases in blood pressure compared with those without altered perception in a community-based cohort. METHODS AND RESULTS: The study included 5190 Chinese adults (4058 men and 1132 women) who were normotensive at baseline. Taste and smell perception were assessed via questionnaire in 2012 (baseline). Blood pressure was measured in 2012 and 2014 to determine relative change in blood pressure. Mean differences of 2-year blood pressure change and 95% confidence intervals (CIs) across four categories of taste and smell perception were calculated after adjusting for known risk factors for hypertension. After adjusting for potential confounders, individuals with altered taste and smell perception had larger increases in systolic blood pressure (adjusted mean difference = 5.1 mmHg, 95% CI: 0.1-10.0, p-value: 0.04) and mean arterial pressure (adjusted mean difference = 3.8 mmHg, 95% CI: 0.4-7.1, p-value: 0.03) after two years of follow-up compared with those having neither altered taste nor altered smell perception. No significant association was observed in individuals with altered taste or smell perception only. CONCLUSION: Our results suggest an association between chemosensory function and blood pressure.

Recent advancements in the mitigation of obnoxious nitrogenous gases.

Nitrogenous gaseous emissions commonly have an obnoxious odor associated with it, which when discharged into the environment results in serious environmental problems and health hazards. Several strategies for mitigation of nitrogenous odorants have been reported which include physical, chemical and biological methods. Biological treatments are widely employed because of their efficiency even at low concentration, where physical and chemical methods are not effective. Most commonly used biological treatment methods are biofiltration, biotrickling filters and membrane bioreactors with innovative reactor design, mixing pattern, and air sparging, for example FEBR, ALR, etc. These treatment methods require a critical assessment for the mitigation of obnoxious nitrogen emissions, especially in the context of environmental protection. This review offers a critical evaluation of treatment methods for the mitigation of nitrogenous odorous compound with a key emphasis on biological treatment systems. Also, various mathematical modelling techniques required for optimized operation of biotreatment systems has been discussed.

In vitro macrophage activation: A technique for screening anti-inflammatory, immunomodulatory and anticancer activity of phytomolecules.

Macrophage activation plays a significant role in homeostasis of organisms. Various internal and external stress factors may affect their function, leading to adverse effects on the body. 'In vitro macrophage activation techniques provide us with a window to understand the mechanisms of inflammation and response of macrophages to the modulating interventions. Apart from infectious diseases, inflammation is also the major culprit in pathogenesis of many noncommunicable diseases such as arthritis, obesity, metabolic syndrome, diabetes, cancer, cardiovascular disease etc. In vitro macrophage activation allows us to study the role of polarized macrophages in the process of pathogenesis. This emerging technique leads to newer diagnostics, understanding pathophysiological mechanism/s, drug development and management of chronic inflammatory diseases. We, at MRC-KHS, use this technique for screening of medicinal plant-derived phytomolecules for their anti-inflammatory, immunomodulatory and anticancer activities. This review briefly outlines the different experimental models of in vitro macrophage activation and their applications for understanding the pathophysiological mechanisms of underlying chronic inflammation and screening of therapeutic activity of plant-based phytomolecules.

The Heart-health Associated Research, Dissemination and Intervention in the Community (HARDIC) Trial for Nepalese Mothers regarding Diet and Physical Activity: A Process Evaluation.

Background Mothers with young children in the peri-urban Jhaukhel-Duwakot Health Demographic Surveillance site of Bhaktapur district have misconceptions and poor behavioural practice regarding diet and physical activity. We developed the Hearthealth Associated Research, Dissemination and Intervention in the Community trial - a health promotion intervention for mothers. Objective The objective of this study was to evaluate the intervention's feasibility, acceptability, potential for transferability and scaling up, and to determine its immediate outcome. Method Duwakot and Jhaukhel were randomly selected as the intervention and control communities, respectively. We trained 47 peer mothers from Duwakot, each of whom gave classes with 10 fellow mothers of their neighbourhood. The process evaluation was carried out on a continuous basis at different points of the intervention held from August to November 2016. Result In round one, the participation and completion rates were both > 90% for peer mothers; and 85% and 70%, respectively, for the fellow mothers. However, the participation rates fell in the round two of the intervention. On the whole, the mothers expressed satisfaction and acceptance of the course content and training modality. Immediate evaluation of the intervention showed improvement of knowledge, attitude and practice of diet and physical activity among both groups of mothers. Conclusion The successful implementation of the intervention targeting diet and physical activity clearly demonstrates the feasibility of health promotional activities in the Nepalese community for improvement of cardiovascular health.

Abdominal Wall Transplantation: Skin as a Sentinel Marker for Rejection.

Abdominal wall transplantation (AWTX) has revolutionized difficult abdominal closure after intestinal transplantation (ITX). More important, the skin of the transplanted abdominal wall (AW) may serve as an immunological tool for differential diagnosis of bowel dysfunction after transplant. Between August 2008 and October 2014, 29 small bowel transplantations were performed in 28 patients (16 male, 12 female; aged 41 ± 13 years). Two groups were identified: the solid organ transplant (SOT) group (n = 15; 12 ITX and 3 modified multivisceral transplantation [MMVTX]) and the SOT-AWTX group (n = 14; 12 ITX and 2 MMVTX), with the latter including one ITX-AWTX retransplantation. Two doses of alemtuzumab were used for induction (30 mg, 6 and 24 h after reperfusion), and tacrolimus (trough levels 8-12 ng/mL) was used for maintenance immunosuppression. Patient survival was similar in both groups (67% vs. 61%); however, the SOT-AWTX group showed faster posttransplant recovery, better intestinal graft survival (79% vs. 60%), a lower intestinal rejection rate (7% vs. 27%) and a lower rate of misdiagnoses in which viral infection was mistaken and treated as rejection (14% vs. 33%). The skin component of the AW may serve as an immune modulator and sentinel marker for immunological activity in the host. This can be a vital tool for timely prevention of intestinal graft rejection and, more important, avoidance of overimmunosuppression in cases of bowel dysfunction not related to graft rejection.

Functional outcome of autologous anorectal transplantation in an experimental model.

BACKGROUND: Although anorectal transplantation is a challenging procedure, it is a promising option for patients who have completely lost anorectal function or in whom it failed to develop, as in congenital malformations. The paucity of animal models with which to test functional outcomes was addressed in this study of anorectal manometry in rats. METHODS: Wistar rats were assigned randomly to four groups: orthotopic anorectal transplantation, heterotopic transplantation, sham operation, or normal control. Bodyweight and anal pressure were measured immediately before and after operation, and on postoperative days 7 and 14. ANOVA and Tukey's test were used to compare results for bodyweight, anal manometry and length of procedure. RESULTS: Immediately after the procedure, mean(s.d.) anal pressure in the orthotopic group (n = 13) dropped from 31·4(13·1) to 1·6(13·1) cmH2 O (P < 0·001 versus both sham operation (n = 13) and normal control (n = 15)), with partial recovery on postoperative day 7 (14·9(13·9) cmH2 O) (P = 0·009 versus normal control) and complete recovery on day 14 (23·7(12·2) cmH2 O). Heterotopic rats (n = 14) demonstrated partial functional recovery: mean(s.d.) anal pressure was 26·9(10·9) cmH2 O before operation and 8·6(6·8) cmH2 O on postoperative day 14 (P < 0·001 versus both sham and normal control). CONCLUSION: Orthotopic anorectal transplantation may result in better functional outcomes than heterotopic procedures. Surgical relevance Patients with a permanent colostomy have limited continence. Treatment options are available, but anorectal transplantation may offer hope. Some experimental studies have been conducted, but available data are currently insufficient to translate into a clinical option. This paper details functional outcomes in a rat model of anorectal autotransplantation. It represents a step in the translational research that may lead to restoration of anorectal function in patients who have lost or have failed to develop it.

Remote revascularization of abdominal wall transplants using the forearm.

Primary abdominal wall closure following small bowel transplantation is frequently impossible due to contraction of the abdominal domain. Although abdominal wall transplantation was reported 10 years ago this, technique has not been widely adopted, partly due to its complexity, but largely because of concerns that storing the abdominal allograft until the end of a prolonged intestinal transplant procedure would cause severe ischemia-reperfusion injury. We report six cases of combined small bowel and abdominal wall transplantation where the ischemic time was minimized by remotely revascularizing the abdominal wall on the forearm vessels, synchronous to the intestinal procedure. When the visceral transplant was complete, the abdominal wall was removed from the forearm and revascularized on the abdomen (n = 4), or used to close the abdomen while still vascularized on the forearm (n = 2). Primary abdominal wall closure was achieved in all. Mean cold ischemia was 305 min (300-330 min), and revascularization on the arm was 50 min (30-60 min). Three patients had proven abdominal wall rejection, all treated successfully. Immediate revascularization of the abdominal wall allograft substantially reduces cold ischemia without imposing constraints on the intestinal transplant. Reducing storage time may also have benefits with respect to ischemia-reperfusion-related graft immunogenicity.

Measurement of right atrial volume and diameters in healthy Nepalese with normal echocardiogram.

BACKGROUND: The size of right atrium is expected to be different in diverse healthy ethnic groups. It is important to know the normal size of right atrium in our healthy population. OBJECTIVE: The study aimed to find out the normal values of right atrial volume, right atrial short axis diameter and right atrial long axis diameter in healthy Nepalese population with normal echocardiographic findings. It also looked at correlations between right atrial dimensions and the right atrial volume. METHOD: Verbal consent was taken from all the participants. One hundred participants between the age of 18 and 60 years with normal echocardiographic findings and without any chronic disease were included in this study. Right atrial volume was measured by using area length method. Right atrial short axis diameter and Right atrial long axis diameter were measured in the four chamber view. RESULT: The mean right atrial volume was 23.64±5.36 ml (range 11.30-40.00 ml).The range of right atrial short axis diameter and right atrial long axis diameter were 1.34-3.80 cm and 2.4-4.7 cm respectively. CONCLUSION: The size of right atrium in the Nepalese population is smaller compared to western population. Male right atrial volume size is greater than female in Nepalese population similar to western population. The findings of normal value of right atrial volume and right atrial diameter in Nepalese population will help the physician to assess patients with various conditions affecting the right atrium.

A single center experience of abdominal wall graft rejection after combined intestinal and abdominal wall transplantation.

We report our outcomes following combined intestinal and abdominal wall transplantation, focusing on the presentation and treatment of acute rejection of the abdominal wall vascularized composite allograft (VCA). Retrospective analysis of all patients with combined intestinal/VCA transplantation was undertaken. Graft abnormalities were documented photographically and biopsies taken, with histological classification of rejection according to Banff 2007 guidelines. We have performed five combined intestinal and abdominal wall transplants to date. Two patients developed erythematous, maculopapular to papular eruptions confined to the VCA, histologically confirmed as grade II/III rejection, yet with normal bowel on endoscopy. Both patients' rashes resolved within 72 h of increasing immunosuppressive treatment. One patient later developed a recurrence of the rash, confirmed as skin rejection, but did not immediately seek medical attention. Treatment was therefore delayed, and mild intestinal rejection developed. We describe the rash associated with VCA rejection, and propose that while the skin of an abdominal wall VCA may reject independently of the intestinal allograft, delay in treatment of rejection episodes may result in rejection of the intestinal graft.

Cost-effectiveness of vascular access for haemodialysis: arteriovenous fistulas versus arteriovenous grafts.

BACKGROUND: The use of an arteriovenous fistula (AVF) for haemodialysis treatment may be associated with a high early failure rate, but usually good long-term patency, while using an arteriovenous graft (AVG) yields a lower early failure rate with worse long-term patency. The aim of this study was to calculate and compare the costs and outcome of AVF and AVG surgery in terms of early and long-term patencies. METHODS: A decision tree and a Markov model were constructed to calculate costs and performance of AVFs and AVGs. The model was populated with a retrospective cohort of HD patients receiving their first VA. The outcomes were determined probabilistically with a 5-year follow-up. RESULTS: AVFs were usable for a mean (95% CI) of 28.5 months (24.6-32.5 months), while AVGs showed a patency of 25.5 months (20.0-31.2 months). The use of AVFs was the dominant type of VA and € 631 could be saved per patient/per month patency compared to AVG use. Regardless of the willingness to pay, the use of AVFs yielded a higher probability of being cost-effective compared to AVGs. CONCLUSIONS: AVFs are more cost-effective than AVGs. Nonetheless, early failure rates significantly influence AVF performance and initiatives to reduce early failure can improve its cost-effectiveness.

Stability analysis of 4-species Aß aggregation model: A novel approach to obtaining physically meaningful rate constants.

Protein misfolding and concomitant aggregation towards amyloid formation is the underlying biochemical commonality among a wide range of human pathologies. Amyloid formation involves the conversion of proteins from their native monomeric states (intrinsically disordered or globular) to well-organized, fibrillar aggregates in a nucleation-dependent manner. Understanding the mechanism of aggregation is important not only to gain better insight into amyloid pathology but also to simulate and predict molecular pathways. One of the main impediments in doing so is the stochastic nature of interactions that impedes thorough experimental characterization and the development of meaningful insights. In this study, we have utilized a well-known intermediate state along the amyloid-ß peptide aggregation pathway called protofibrils as a model system to investigate the molecular mechanisms by which they form fibrils using stability and perturbation analysis. Investigation of protofibril aggregation mechanism limits both the number of species to be modeled (monomers, and protofibrils), as well as the reactions to two (elongation by monomer addition, and protofibril-protofibril lateral association). Our new model is a reduced order four species model grounded in mass action kinetics. Our prior study required 3200 reactions, which makes determining the reaction parameters prohibitively difficult. Using this model, along with a linear perturbation argument, we rigorously determine stable ranges of rate constants for the reactions and ensure they are physically meaningful. This was accomplished by finding the ranges in which the perturbations dieout in a five-parameter sweep, which includes the monomer and protofibril equilibrium concentrations and three of the rate constants. The results presented are a proof-of-concept method in determining meaningful rate constants that can be used as a bonafide way for determining accurate rate constants for other models involving complex biological reactions such as amyloid aggregation.

Transversus abdominis plane blocks in laparoscopic inguinal hernia repair: a review.

INTRODUCTION: Throughout its history, there have been significant advances in pain control of inguinal hernia repairs. One of the most recent developments is locoregional pain blocks. There is a multitude of literature available on laparoscopic inguinal hernia repair and transversus abdominis plane (TAP) blocks. OBJECTIVES: This paper seeks to provide a thorough and systematic literature review on the role of TAP blocks in laparoscopic inguinal hernia repairs. METHODS: PubMed and Google Scholar were searched for relevant literature using predetermined medical subject heading (MeSH) terms: "(TAP block)" AND "(Laparoscopic inguinal hernia repair)". RESULTS: A total of 166 publications were identified, from which 18 publications were included in the final review after eligibility criteria were applied. CONCLUSION: The majority of studies conclude that TAP blocks performed in the setting of laparoscopic inguinal hernia repair improve post-operative pain and mobility, decrease opiate analgesic usage, and are superior in pain control compared to other modalities of regional anesthesia. Thus, to improve post-operative outcomes and patient satisfaction, TAP blocks should be heavily considered for routine use in surgical practice for laparoscopic inguinal hernia repair.