Protein modeling of apical membrane antigen-1(AMA-1) of Plasmodium cynomolgi

Apical membrane Antigen-1(AMA-1), an asexual blood stage antigen of Plasmodium cynomolgi, is an important candidate for testing as a component of malarial vaccine. The degree of conservation ofAMA-1 sequences implies a conserved function for this molecule across different species of Plasmodium. Since the AMA-1 of plasmodium cyanomolgi is yet to be structured, the authors have generated a homology model of AMA-1 by using the Swiss-PDB server. The protein’s conservity has been verified by performing multiple alignments using Bioedit and conserved domain database. The model was further checked for its correctness by predicting 2D and 3D structures, which validates thestructure

RELIABILITY OF 3D FRONTAL PLANE KNEE AB/ADDUCTION RANGE OF MOTION DURING RUNNING IN YOUNG ATHLETES

This study quantified within-session and between-session reliability of 3D frontal plane knee ab/adduction range of motion during the stance phase of running gait calculated for 18 long term athlete development programme participants (10 males and 8 females, 11.5 ±1.4 years) during two testing sessions (spaced 10 weeks apart). Average mean differences in frontal plane knee ab/adduction between running trials (for the right or left side) within a session (week 1 or week 10) ranged from 0.2 to 7.2% (ES 0.01–0.26) which were acceptable differences. However, average mean differences between sessions for running trials (for the right or left side) ranged from 0.1 to 20% (ES 0.01–0.6). The mixed model resulted in estimates of knee ab/adduction range of motion for effects of limb side (3.6°), session (2.8°), run trial (0.2°) and subjects (4.5°). Within-session ICCs ranged from 0.80 to 0.92 and between-session ICCs ranged from 0.51 to 0.73. Based on these ICCs, within-session reliability of frontal plane knee ab/adduction is good and between-session reliability is average to good

Objective assessment of progressive increase in bite force post surgical correction of mandibular fractures using Nupai bite scan analyser

Background: Fracture of mandible is a common condition which is increasing in incidence in the trauma centers due to increasing motor vehicles and failure to abide by traffic regulations. Patients undergo surgical open reduction and internal fixation where post-operative occlusion and normal masticatory functions are targeted. Bite force can be taken as a guide of normal masticatory function of an individual which is dependent upon craniomandibular biomechanics. The aim of the study was to analyse bite force measurements post-operatively in patients who underwent open reduction and internal fixation for mandible fractures at different sites.Methods: Molar bite force was recorded in 31 post-operative patients who underwent open surgical procedure for fracture mandible in the department of plastic surgery from January 2018 to June 2019 by a pre-scale bite force recorder-Nupai bite force prescale system (FujiTM). Various parameters were recorded pre and post-operatively including age, gender, history, comorbidities, requirement of MMF, site and number of fractures and age of injury. Bite force were compared and improvement of bite force every 2 weeks was noted and analyzed upto 6 weeks postoperatively.Results: Bite force improvement was seen in all types of mandible fractures irrespective of the site and type of fractures over a period of 6 weeks post-operatively. This improvement was however not statistically significant. Decreased time interval form injury to surgery resulted in improved bite force measurements though not statistically significant.Conclusions: Although objective improvement in bite force could be demonstrated but extensive study involving more subjects and more patient variables would have statistical significance

The Proportion of Lower Limb Running Injuries by Gender, Anatomical Location and Specific Pathology

Running is associated with a higher risk of overuse injury than other forms of aerobic exercise such as walking, swimming and cycling. An accurate description of the proportion of running injuries per anatomical location and where possible, per specific pathology, for both genders is required. The aim of this review was to determine the proportion of lower limb running injuries by anatomical location and by specific pathology in male and female runners (≥800m - ≤ marathon). The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed for this review. A literature search was performed with no restriction on publication year in Web of Science, Scopus, Sport-Discus, PubMed, and CINAHL up to July 2017. Retrospective, cross-Sectional, prospective and randomised-controlled studies which surveyed injury data in runners were included. 36 studies were included to report the overall proportion of injury per anatomical location. The overall proportion of injury by specific pathology was reported from 11 studies. The knee (28%), ankle-foot (26%) and shank (16%) accounted for the highest proportion of injury in male and female runners, although the proportion of knee injury was greater in women (40% vs. 31%). Relative to women, men had a greater proportion of ankle-foot (26% vs. 19%) and shank (21% vs. 16%) injuries. Patellofemoral pain syndrome (PFPS; 17%), Achilles tendinopathy (AT; 10%) and medial tibial stress syndrome (MTS; 8%) accounted for the highest proportion of specific pathologies recorded overall. There was insufficient data to sub-divide specific pathology between genders. The predominate injury in female runners is to the knee. Male runners have a more even distribution of injury between the knee, shank and ankle-foot complex. There are several methodological issues, which limit the interpretation of epidemiological data in running injury

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample siz

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high

Immune interaction between SARS-CoV-2 and Mycobacterium tuberculosis

SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) are major infectious causes of death, with meta-analyses and population-based studies finding increased mortality in co-infected patients simultaneously diagnosed with COVID-19 and tuberculosis (TB). There is a need to understand the immune interaction between SARS-CoV-2 and Mtb which impacts poor outcomes for those co-infected. We performed a PubMed and preprint search using keywords [SARS-CoV-2] AND [tuberculosis] AND [Immune response], including publications after January 2020, excluding reviews or opinions. Abstracts were evaluated by authors for inclusion of data specifically investigating the innate and/or acquired immune responses to SARS-CoV-2 and Mtb in humans and animal models, immunopathological responses in co-infection and both trials and investigations of potential protection against SARS-CoV-2 by Bacille Calmette Guérin (BCG). Of the 248 articles identified, 39 were included. Incidence of co-infection is discussed, considering in areas with a high burden of TB, where reported co-infection is likely underestimated. We evaluated evidence of the clinical association between COVID-19 and TB, discuss differences and similarities in immune responses in humans and in murine studies, and the implications of co-infection. SARS-CoV-2 and Mtb have both been shown to modulate immune responses, particularly of monocytes, macrophages, neutrophils, and T cells. Co-infection may result in impaired immunity to SARS-CoV-2, with an exacerbated inflammatory response, while T cell responses to Mtb may be modulated by SARS-CoV-2. Furthermore, there has been no proven potential COVID-19 clinical benefit of BCG despite numerous large-scale clinical trials

Tumor Drug Penetration Measurements Could Be the Neglected Piece of the Personalized Cancer Treatment Puzzle

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150514/1/cpt1211.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150514/2/cpt1211_am.pd

Chronic disease prevention programs offered by Aboriginal Community Controlled Health Services in New South Wales, Australia

Objectives: To identify and describe chronic disease prevention programs offered by Aboriginal Community Controlled Health Services (ACCHSs) in New South Wales (NSW), Australia. Methods: ACCHSs were identified through the Aboriginal Health and Medical Research Council of NSW website. Chronic disease programs were identified from the Facebook page and website of each ACCHS. Characteristics, including regions, target population, condition, health behaviour, modality and program frequency were extracted and summarised. Results: We identified 128 chronic disease programs across 32 ACCHSs. Of these, 87 (68%) programs were broad in their scope, 20 (16%) targeted youth, three (2%) targeted Elders, 16 (12%) were for females only and five (4%) were for males only. Interventions included physical activity (77, 60%), diet and nutrition (74, 58%), smoking (70, 55%), and the Aboriginal and Torres Strait Islander Health Check (44, 34%), with 93 programs (73%) of ongoing duration. Conclusions: Chronic disease prevention programs address chronic conditions by promoting physical activity, diet and nutrition, smoking cessation and health screening. Most target the general Aboriginal community, a few target specific groups based on gender and age, and more than one‐quarter are time‐limited. Implications for public health: Chronic disease programs that are co‐produced with specific groups, based on age and gender, may be needed.Victoria Sinka, Pamela Lopez‐Vargas, Allison Tong, Michelle Dickson, Marianne Kerr, Noella Sheerin ... et al

A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function.

INTRODUCTION: Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), a biomarker of AKI, induces interferon-γ expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells following inflammasome activation. This phase IIa, single-arm trial assessed the effect of a single dose of GSK1070806 on DGF occurrence post donation after circulatory death (DCD) kidney transplantation. METHODS: The 3 mg/kg intravenous dose was selected based on prior studies and physiologically based pharmacokinetic (PBPK) modeling, indicating the high likelihood of a rapid and high level of IL18 target engagement when administered prior to kidney allograft reperfusion. Utilization of a Bayesian sequential design with a background standard-of-care DGF rate of 50% based on literature, and confirmed via extensive registry data analyses, enabled a statistical efficacy assessment with a minimal sample size. The primary endpoint was DGF frequency, defined as dialysis requirement ≤7 days post transplantation (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics and pharmacodynamic biomarkers. RESULTS: GSK1070806 administration was associated with IL18-GSK1070806 complex detection and increased total serum IL18 levels due to IL18 half-life prolongation induced by GSK1070806 binding. Interferon-γ-induced chemokine levels declined or remained unchanged in most patients. Although the study was concluded prior to the Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate, and an additional two patients, although not reaching the protocol-defined DGF definition, demonstrated poor graft function. Six of seven patients experienced serious adverse events (SAEs), including two treatment-related SAEs. CONCLUSION: Overall, using a Bayesian design and extensive PBPK dose modeling with only a small sample size, it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF in the enrolled DCD transplant population. TRIAL REGISTRATION: NCT02723786