Perspective of medical undergraduates in India towards the LGBTQIA+ population: a short insight into changes in the medical curriculum.

BACKGROUND: Understanding the attitudes of medical students towards individuals from the lesbian, gay, bisexual, transgender, queer, questioning, intersex and asexual (LGBTQIA+) community is a prerequisite for informing competencies-based medical education (CBME) guidelines to make them LGBTQIA+ inclusive. The present study was conducted to assess the attitudes of medical undergraduate students from Indian medical colleges towards the LGBTQIA+ community. METHODS: An online cross-sectional survey was conducted in medical undergraduate students across India, which measured the opinions, beliefs, and acceptance of LGBTQIA+ people using a structured questionnaire uploaded on Google Forms. After data collection, the datasheet was downloaded, cleaned, and anonymised before being imported into RStudio for analysis. RESULTS: A total of 273 valid entries were assessed from the online survey. There was significant gender-based differences on most traditional opinions and beliefs regarding the LGBTQIA+ population (P <0.05). The female participants appeared to be more accepting of and comfortable with all denominations of LGBTQIA+. Many of the participants believed that members of the LGBTQIA+ community are more prone to sexually transmitted diseases, especially HIV/AIDS. However, a few participants also opined that the increased susceptibility to HIV/AIDS may be due to increased prevalence of intravenous drug abuse in the LGBTQIA+ community. CONCLUSIONS: There are some misconceptions about the LGBTQIA+ community among medical students. Therefore, in order to ensure LGBTQIA+ sensitive healthcare provision, there needs to be a concerted, informed effort to incorporate necessary changes in the CBME curriculum.

Polio outbreak investigation and response in Somalia, 2013.

BACKGROUND: For >2 decades, conflicts and recurrent natural disasters have maintained Somalia in a chronic humanitarian crisis. For nearly 5 years, 1 million children <10 years have not had access to lifesaving health services, including vaccination, resulting in the accumulation by 2012 of the largest geographically concentrated cohort of unvaccinated children in the world. This article reviews the epidemiology, risk, and program response to what is now known as the 2013 wild poliovirus (WPV) outbreak in Somalia and highlights the challenges that the program will face in making Somalia free of polio once again. METHODS: A case of acute flaccid paralysis (AFP) was defined as a child <15 years of age with sudden onset of fever and paralysis. Polio cases were defined as AFP cases with stool specimens positive for WPV. RESULTS: From 9 May to 31 December 2013, 189 cases of WPV type 1 (WPV1) were reported from 46 districts of Somalia; 42% were from Banadir region (Mogadishu), 60% were males, and 93% were <5 years of age. All Somalian polio cases belonged to cluster N5A, which is known to have been circulating in northern Nigeria since 2011. In response to the outbreak, 8 supplementary immunization activities were conducted with oral polio vaccine (OPV; trivalent OPV was used initially, followed subsequently by bivalent OPV) targeting various age groups, including children aged <5 years, children aged <10 years, and individuals of any age. CONCLUSIONS: The current polio outbreak erupted after a polio-free period of >6 years (the last case was reported in March 2007). Somalia interrupted indigenous WPV transmission in 2002, was removed from the list of polio-endemic countries a year later, and has since demonstrated its ability to control polio outbreaks resulting from importation. This outbreak reiterates that the threat of large polio outbreaks resulting from WPV importation will remain constant unless polio transmission is interrupted in the remaining polio-endemic countries.

Effectiveness of oral polio vaccination against paralytic poliomyelitis: a matched case-control study in Somalia.

BACKGROUND: After the last case of type 1 wild poliovirus (WPV1) was reported in 2007, Somalia experienced another outbreak of WPV1 (189 cases) in 2013. METHODS: We conducted a retrospective, matched case-control study to evaluate the vaccine effectiveness (VE) of oral polio vaccine (OPV). We retrieved information from the Somalia Surveillance Database. A case was defined as any case of acute flaccid paralysis (AFP) with virological confirmation of WPV1. We selected two groups of controls for each case: non-polio AFP cases ("NPAFP controls") matched to WPV1 cases by age, date of onset of paralysis and region; and asymptomatic "neighborhood controls," matched by age. Using conditional logistic regression, we estimated the VE of OPV as (1-odds ratio)×100. RESULT: We matched 99 WPV cases with 99 NPAFP controls and 134 WPV1 cases with 268 neighborhood controls. Using NPAFP controls, the overall VE was 70% (95% confidence interval [CI], 37-86), 59% (2-83) among 1-3 dose recipients, 77% (95% CI, 46-91) among ≥4 dose recipients. In neighborhood controls, the overall VE was 95% (95% CI, 84-98), 92% (72-98) among 1-3 dose recipients, and 97% (89-99) among ≥4 dose recipients. When the analysis was limited to cases and controls ≤24 months old, the overall VE in NPAFP and neighborhood controls was 95% (95% CI, 65-99) and 97% (95% CI, 76-100), respectively. CONCLUSIONS: Among individuals who were fully vaccinated with OPV, vaccination was effective at preventing WPV1 in Somalia.

Gefitinib for oesophageal cancer progressing after chemotherapy (COG): a phase 3, multicentre, double-blind, placebo-controlled randomised trial.

BACKGROUND: Evidence is scarce for the effectiveness of therapies for oesophageal cancer progressing after chemotherapy, and no randomised trials have been reported. We aimed to compare gefitinib with placebo in previously treated advanced oesophageal cancer. METHODS: For this phase 3, parallel, randomised, placebo-controlled trial, eligible patients were adults with advanced oesophageal cancer or type I/II Siewert junctional tumours, histologically confirmed squamous-cell carcinoma or adenocarcinoma, who had progressed after chemotherapy, with WHO performance status 0-2, and with measurable or evaluable disease on CT scan. Participants were recruited from 48 UK centres and randomly assigned (1:1) to gefitinib (500 mg) or matching placebo by simple randomisation with no stratification factors. Patients, clinicians, and trial office staff were masked to treatment allocation. Treatment continued until disease progression, unacceptable toxicity, or patient choice. The primary outcome was overall survival, analysed by intention to treat. This trial is registered, number ISRCTN29580179. FINDINGS: Between March 30, 2009, and Nov 18, 2011, 450 patients were randomly assigned to treatment groups (one patient withdrew consent; 224 patients allocated gefitinib and 225 allocated placebo included in analyses). Overall survival did not differ between groups (median 3·73 months, 95% CI 3·23-4·50, for gefitinib vs 3·67 months, 95% CI 2·97-4·37, for placebo; hazard ratio [HR] 0·90, 95% CI 0·74-1·09, p=0·29). Among the prespecified patient-reported outcomes (110 patients on gefitinib and 121 on placebo completed both baseline and 4 week questionnaires and were included in analyses), odynophagia was significantly better in the gefitinib group (adjusted mean difference -8·61, 95% CI -14·49 to -2·73; n=227; p=0·004), whereas the other outcomes were not significantly improved compared with placebo: global quality of life (2·69, 95% CI -2·33 to 7·72, n=231, p=0·293), dysphagia (-3·18, 95% CI -8·36 to 2·00, n=231, p=0·228), and eating (-4·11, 95% CI -9·96 to 1·75, n=229, p=0·168). Median progression-free survival was marginally longer with gefitinib than it was with placebo (1·57 months, 95% CI 1·23-1·90 in the gefitinib group vs 1·17 months, 95% CI 1·07-1·37 in the placebo group; HR 0·80, 95% CI 0·66-0·96, p=0·020). The most common toxicities were diarrhoea (36 [16%] of 224 patients on gefitinib vs six [3%] of 225 on placebo) and skin toxicity (46 [21%] vs two [1%]), both mostly grade 2. The commonest grade 3-4 toxicities were fatigue (24 [11%] vs 13 [6%] patients) and diarrhoea (13 [6%] vs two [1%]). Serious adverse events were reported in 109 (49%) of 224 patients assigned to gefitinib and 101 (45%) of 225 on placebo. 54 (24%) of patients in the gefitinib group achieved disease control at 8 weeks, as did 35 (16%) of patients on placebo (p=0·023). INTERPRETATION: The use of gefitinib as a second-line treatment in oesophageal cancer in unselected patients does not improve overall survival, but has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy. Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients. FUNDING: Cancer Research UK.

Evaluation of a universal long-lasting insecticidal net (LLIN) distribution campaign in Ghana: cost effectiveness of distribution and hang-up activities.

BACKGROUND: Between May 2010 and October 2012, approximately 12.5 million long-lasting insecticidal nets (LLINs) were distributed through a national universal mass distribution campaign in Ghana. The campaign included pre-registration of persons and sleeping places, door-to-door distribution of LLINs with 'hang-up' activities by volunteers and post-distribution 'keep-up' behaviour change communication activities. Hang-up activities were included to encourage high and sustained use. METHODS: The cost and cost-effectiveness of the LLIN Campaign were evaluated using a before-after design in three regions: Brong Ahafo, Central and Western. The incremental cost effectiveness of the 'hang-up' component was estimated using reported variation in the implementation of hang-up activities and LLIN use. Economic costs were estimated from a societal perspective assuming LLINs would be replaced after three years, and included the time of unpaid volunteers and household contributions given to volunteers. RESULTS: Across the three regions, 3.6 million campaign LLINs were distributed, and 45.5% of households reported the LLINs received were hung-up by a volunteer. The financial cost of the campaign was USD 6.51 per LLIN delivered. The average annual economic cost was USD 2.90 per LLIN delivered and USD 6,619 per additional child death averted by the campaign. The cost-effectiveness of the campaign was sensitive to the price, lifespan and protective efficacy of LLINs.Hang-up activities constituted 7% of the annual economic cost, though the additional financial cost was modest given the use of volunteers. LLIN use was greater in households in which one or more campaign LLINs were hung by a volunteer (OR=1.57; 95% CI=1.09, 2.27; p=0.02). The additional economic cost of the hang-up activities was USD 0.23 per LLIN delivered, and achieved a net saving per LLIN used and per death averted. CONCLUSION: In this campaign, hang-up activities were estimated to be net saving if hang-up increased LLIN use by 10% or more. This suggests hang-up activities can make a LLIN campaign more cost-effective.

Rural-urban and racial differences in cesarean deliveries before and during the COVID-19 pandemic in South Carolina.

PROBLEM: Unnecessary cesarean delivery increases the risk of complications for birthing people and infants. BACKGROUND: Examining the intersectionality of rural and racial disparities in low-risk cesarean delivery is necessary to improve equity in quality obstetrics care. AIM: To evaluate rural and racial/ethnic differences in Nulliparous, Term, Singleton, Vertex (NTSV) and primary cesarean delivery rates before and during the COVID-19 pandemic in South Carolina. METHODS: This retrospective cohort study used birth certificates linked to all-payer hospital discharge data for South Carolina childbirths from 2018 to 2021. Multilevel logistic regressions examined differences in cesarean outcomes by rural/urban hospital location and race/ethnicity of birthing people during pre-pandemic (January 2018-February 2020) and peri-pandemic periods (March 2020-December 2021), adjusting for maternal, infant, and hospital characteristics among two low-risk pregnancy cohorts: 1) Nulliparous, Term, Singleton, Vertex (NTSV, n = 65,974) and 2) those without prior cesarean (primary, n = 167,928). FINDINGS: Black vs. White disparities remained for NTSV cesarean in adjusted models (urban pre-pandemic aOR = 1.34, 95 %CI 1.23-1.46) but were not significantly different for primary cesarean, apart from rural settings peri-pandemic (aOR = 0.87, 95 %CI 0.79-0.96). Hispanic individuals had higher adjusted odds of NTSV cesarean only for rural settings pre-pandemic (aOR = 1.28, 95 %CI 1.05-1.56), but this disparity was not significant during the pandemic (aOR = 1.13, 95 %CI 0.93-1.37). DISCUSSION AND CONCLUSION: Observed rural and racial/ethnic disparities in cesarean delivery outcomes were present before and during the COVID-19 pandemic. Strategies effective in reducing racial disparities in primary cesarean may be useful in also reducing Black vs. White NTSV cesarean disparities.

Repurposing surgical wards in pandemics - An appraisal of outcomes of COVID-19 patients treated in Orthopaedic wards.

Background: The COVID-19 pandemic resulted in a shift in the way healthcare resources were used. While India faced limited effects in the first COVID wave primarily due to strict lockdown of the county, it was one of the worst affected in the second wave and at one time reported the highest number of daily cases. To address the lack of intensive care units (ICU) beds, the surgical wards of our institute were repurposed to take care of patients requiring supplementary oxygen and other supportive care till either they improved or an ICU bed was available. The medical personnel in charge of the surgical wards were entrusted with the care of patients with support from intensive care support teams (ICST). Aims: We aimed to examine the clinical details of patients admitted in the repurposed orthopaedic wards during the second COVID wave and to evaluate the factors that might affect the clinical outcomes in such patients. Methods: This was a retrospective review of records of patients admitted in the repurposed orthopaedic wards between 16 April 2021 and 20 May 2021. Details related to demography, COVID-19 presentation, COVID-19-related management and clinical course, including transfers to ICUs, and outcomes in terms of either discharge to home or death were recorded. They were analysed using statistical software. Results: One hundred and twenty three patients were treated during the said period. Twenty patients died during treatment, resulting in a mortality rate of 16.3%. Age, gender, RT-PCR status, pre-existing comorbidities, SpO2 at admission, method of supplemental oxygen supply, total leukocyte counts, haemoglobin values, serum C-reactive protein, Lactate dehydrogenase (LDH) and creatinine values had no statistically significant association with death of a patient during treatment. Conclusion: Based on the results, one can state that clinicians of surgical specialities having background knowledge of internal medicine from undergraduate education can manage patients of COVID-19 with support from ICST with reasonable outcomes. In case of future pandemics, surgical wards can be repurposed to tide over exigencies. Additionally, primary care physicians, who are often the first point of contact for patients, can allay their apprehensions adequately in future pandemics, thus preventing widespread panic and burdening of healthcare resources.

The chaperone-assisted E3 ligase C terminus of Hsc70-interacting protein (CHIP) targets PTEN for proteasomal degradation.

The tumor suppressor, PTEN is key to the regulation of diverse cellular processes, making it a prime candidate to be tightly regulated. The PTEN level is controlled in a major way by E3 ligase-mediated degradation through the Ubiquitin-Proteasome System (UPS). Nedd 4-1, XIAP, and WWP2 have been shown to maintain PTEN turnover. Here, we report that CHIP, the chaperone-associated E3 ligase, induces ubiquitination and regulates the proteasomal turnover of PTEN. It was apparent from our findings that PTEN transiently associates with the molecular chaperones and thereby gets diverted to the degradation pathway through its interaction with CHIP. The TPR domain of CHIP and parts of the N-terminal domain of PTEN are required for their interaction. Overexpression of CHIP leads to elevated ubiquitination and a shortened half-life of endogenous PTEN. On the other hand, depletion of endogenous CHIP stabilizes PTEN. CHIP is also shown to regulate PTEN-dependent transcription presumably through its down-regulation. PTEN shared an inverse correlation with CHIP in human prostate cancer patient samples, thereby triggering the prospects of a more complex mode of PTEN regulation in cancer.

Mechanism of ß-catenin-mediated transcriptional regulation of epidermal growth factor receptor expression in glycogen synthase kinase 3 ß-inactivated prostate cancer cells.

Wnt/ß-catenin and EGFR pathways are important in cancer development and often aberrantly activated in human cancer. However, it is very important to understand the mechanism responsible for this activation and the relation between them. Here, we report the mechanism of EGFR expression by transcriptionally active ß-catenin in GSK3ß-inactivated prostate cancer cells that eventually leads to its enhanced proliferation and survival. Expressions of ß-catenin and EGFR are elevated in various cancers specifically in prostate cancer cells, DU145. When GSK3ß is inactivated in these cells, ß-catenin gets stabilized, phosphorylated at Ser-552 by protein kinase A, accumulates in the nucleus, and regulates the expression of its target genes that include EGFR. Chromatin immunoprecipitation (ChIP) and promoter analysis revealed that the EGFR promoter gets occupied by transcriptionally active ß-catenin when elevated in GSK3ß-inactivated cells. This phenomenon not only leads to increased expression of EGFR but also initiates the activation of its downstream molecules such as ERK1/2 and Stat3, ultimately resulting in up-regulation of multiple genes involved in cell proliferation and survival.

How to make services adolescent friendly? A cross-sectional study on awareness of adolescent friendly health clinics in Central India.

Background: India's flagship program on adolescent health - Rashtriya Kishor Swasthya Karyakram (RKSK) emphasises the importance of strengthening Adolescent Friendly Health Clinics (AFHCs) under its facility-based approach for improving the health of adolescents. AFHCs are intended to provide targeted intervention in six domains - nutrition, injuries & violence (including gender-based violence), mental health, sexual & reproductive health, substance abuse and noncommunicable diseases. Objective: The current study was conducted to assess the determinants of awareness and utilisation of AFHC services in districts with RKSK services in Madhya Pradesh. Subjects: In total, 1605 adolescents (both males and females) within the age group of 10-19 years were included in the study. Methods: Multistage stratified random sampling was employed to enrol participants from three districts of Madhya Pradesh, where AFHC services have been launched. Results: The mean age of the participants was 15.07 ± 2.32 years. Only 153 (9.5%) adolescents were aware of AFHC services. On multivariate logistic regression, awareness of AFHC was seen to be associated with being aware of RKSK, being a part of the peer educator-led peer group, having had adolescent health days organised in the village and belonging from one of the financially better off districts. Utilisation rate of AFHC services was lower still - at 2.74%. Conclusion: Both awareness and utilisation of AFHC services remain very low among adolescents. There is a pressing need to focus on awareness generation campaigns - via mass media, but more importantly, through community health workers and peer educators - in order to sensitise target beneficiaries about the available services.

Ankle and Hindfoot Alignment Changes in Advanced OA Varus Knees After Cruciate Retaining Total Knee Arthroplasty: A Prospective Cohort Study.

Background: Correct alignment of the knee is considered to be one of the most influential factors in determining the long-term outcomes after Total Knee Arthroplasty (TKA), and is believed to decrease both the mechanical and shear stresses placed on the bearing surfaces, as well as the bone/prosthesis interfaces. Compensatory malalignment of ankle and hindfoot is a recognized cause for ankle disability and deformity in long-standing osteoarthritic patients with varus deformity. This study aims to assess changes in ipsilateral ankle and hindfoot if any, pre- and post-operative TKA. Methods: 65 knees of 54 patients of osteoarthritis knee were evaluated for alignment in knee, ankle and hindfoot pre- and post-TKA. Pre- and post-operative scanogram were evaluated for knee and ankle alignment. Hindfoot alignment view was used to calculate hindfoot alignment angle. All parameters were compared before TKA and after 10 weeks TKA and Wilcoxon signed rank test was used to test the significance of the values. Results: Mean age of the patients was 62.9 years (49-80 years). Mean varus before surgery was 14.49 which changed to 4.01 and mean hindfoot angle valgus reduced from 9.23 to 6.62, both of which was found significant. Significant changes were also observed between pre- and post-op measurements of knee society scores, AOFAS, with improved functional outcomes both in knee and ankle. Conclusion: This study reveals the radiological and functional changes occurring in the ankle and hindfoot after acute correction of long-standing varus deformity of the knee using total knee arthroplasty. Hindfoot valgus alignment in varus knees decreased significantly post-TKA without any intervention at ankle level. In cases undergoing knee arthroplasty, effect of the acute change in the alignment of the knee on the ankle and hindfoot should be taken into consideration and the amount of correction of knee alignment can be a predictor of correction of ankle and hindfoot malalignment too. The lateral benefit of improvement in ankle pain after TKA is a significant gain in this study.

Comparison of cognition and alexithymia in patients of schizophrenia with and without comorbid alcohol use: A cross-sectional exploratory study.

Background: Cognitive impairment and alexithymia are commonly associated with schizophrenia and alcohol use disorder independently. Both can lead to poor prognosis and recovery. In patients with dual diagnosis, this association can be more prevalent and severe. Materials and Methods: A total of 75 participants were grouped into two (35 each): Group A, a Schizophrenia group and Group B with comorbid alcohol use. Sociodemographic factors, clinical profile, cognitive functions, and alexithymia were compared between the two groups using semi-structured pro forma, Positive and Negative Syndrome Scale, Alcohol Use Disorders Identification Test (AUDIT), Montreal Cognitive Assessment (MoCA) Scale, Toronto Alexithymia Scale (TAS-20) (subcategorized into three subscales (1) "Difficulty describing feelings" (DDF), (2) "Difficulty identifying feeling" (DIF), and (3) "Externally-Oriented Thinking" and Brief Psychiatric Rating Scale. Statistical analysis was performed using the Chi-square tests and t-tests as applicable. P < 0.05 was considered statistically significant. Results: The mean age of the participants was 33.61 (standard deviation [SD]-8.11), mean duration of schizophrenia was 70.8 months (SD-47.5) and mean duration of alcohol consumption was 9.10 years (SD-7.7). MoCA score was significantly lower (mean-21.80, SD-2.98) and TAS total score was significantly higher in Group B (Mean-67.31, SD-8.10). DDF (Mean-19.28, SD-4.02) and DIF scores (Mean-22.86, SD-4.66) were significantly higher in alcohol group compared to nonalcohol group. Furthermore, MoCA score was significantly impaired and TAS total, DDF and DIF scores were significantly higher in participants with AUDIT score >8 (P < 0.05). Lower score on MoCA correlated with the higher score of alexithymia. Conclusion: Cognitive dysfunction and alexithymia were significantly more in patients of schizophrenia with comorbid alcohol use and positively correlated with the severity of alcohol use disorder.

A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes.

INTRODUCTION: Trauma accounts for nearly 10% of the global burden of disease. Several trauma life support programmes aim to improve trauma outcomes. There is no evidence from controlled trials to show the effect of these programmes on patient outcomes. We describe the protocol of a pilot study that aims to assess the feasibility of conducting a cluster randomised controlled trial comparing advanced trauma life support (ATLS) and primary trauma care (PTC) with standard care. METHODS AND ANALYSIS: We will pilot a pragmatic three-armed parallel, cluster randomised controlled trial in India, where neither of these programmes are routinely taught. We will recruit tertiary hospitals and include trauma patients and residents managing these patients. Two hospitals will be randomised to ATLS, two to PTC and two to standard care. The primary outcome will be all-cause mortality at 30 days from the time of arrival to the emergency department. Our secondary outcomes will include patient, provider and process measures. All outcomes except time-to-event outcomes will be measured both as final values as well as change from baseline. We will compare outcomes in three combinations of trial arms: ATLS versus PTC, ATLS versus standard care and PTC versus standard care using absolute and relative differences along with associated CIs. We will conduct subgroup analyses across the clinical subgroups men, women, blunt multisystem trauma, penetrating trauma, shock, severe traumatic brain injury and elderly. In parallel to the pilot study, we will conduct community consultations to inform the planning of the full-scale trial. ETHICS AND DISSEMINATION: We will apply for ethics approvals to the local institutional review board in each hospital. The protocol will be published to Clinical Trials Registry-India and ClinicalTrials.gov. The results will be published and the anonymised data and code for analysis will be released publicly.

ISP Good Clinical Practice Recommendations for the management of Dentin Hypersensitivity.

Dentin hypersensitivity (DH) is a rising concern in clinical dentistry that causes pain and discomfort and negatively affects the quality of life of patients. Indian Society of Periodontology conducted a nationwide survey, involving 3000 dentists in December 2020, which revealed significant knowledge gaps regarding DH, viz., under-diagnosis, incorrect differential diagnosis, and treatment strategies/recommendations for the management of DH patients in daily clinical practice. The current paper has been envisioned and conceptualized to update the practicing Indian dentists regarding the so-called enigma of dentistry "Dentin Hypersensitivity," based on the best available contemporary evidence. An expert panel was constituted comprising 30 subject experts from across the country, which after extensive literature review and group discussions formulated these recommendations. The panel advocated routine screening of all dentate patients for exposed dentin areas and DH to avoid under-diagnosis of the condition and suggested an early preventive management. Consensus guidelines/recommendations for the use of desensitizing agents (DAs) at home, including the use of herbal agents, are also provided within the backdrop of the Indian context. The guidelines recommend that active management of DH shall be accomplished by a combination of at home and in-office therapies, starting with the simplest and cost-effective home use of desensitizing toothpastes. A diagnostic decision tree and a flowchart for application in daily practice are designed to manage the patients suffering from DH or presenting with exposed dentin areas in dentition. Various treatment methods to manage DH have been discussed in the paper, including the insights from previously published treatment guidelines. Further, a novel system of classification of DH patients based on specific case definitions has been developed for the first time. Explicit charts regarding the available treatment options and the chronology of institution of the agent, for the management in different case categories of DH, have been provided for quick reference. The management strategy takes into account a decision algorithm based on hierarchy of complexity of treatment options and intends to improve the quality of life of the patient by long-term maintenance with an innovatively defined triple C's or 3Cs approach.

Evidence for a "wattle and daub" model of the cyst wall of entamoeba.

The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen Entamoeba histolytica, is composed of fibrils of chitin and three chitin-binding lectins called Jacob, Jessie3, and chitinase. Here we show chitin, which was detected with wheat germ agglutinin, is made in secretory vesicles prior to its deposition on the surface of encysting Ei. Jacob lectins, which have tandemly arrayed chitin-binding domains (CBDs), and chitinase, which has an N-terminal CBD, were each made early during encystation. These results are consistent with their hypothesized roles in cross-linking chitin fibrils (Jacob lectins) and remodeling the cyst wall (chitinase). Jessie3 lectins likely form the mortar or daub of the cyst wall, because 1) Jessie lectins were made late during encystation; 2) the addition to Jessie lectins to the cyst wall correlated with a marked decrease in the permeability of cysts to nucleic acid stains (DAPI) and actin-binding heptapeptide (phalloidin); and 3) recombinant Jessie lectins, expressed as a maltose-binding proteins in the periplasm of Escherichia coli, caused transformed bacteria to agglutinate in suspension and form a hard pellet that did not dissociate after centrifugation. Jessie3 appeared as linear forms and rosettes by negative staining of secreted recombinant proteins. These findings provide evidence for a "wattle and daub" model of the Entamoeba cyst wall, where the wattle or sticks (chitin fibrils likely cross-linked by Jacob lectins) is constructed prior to the addition of the mortar or daub (Jessie3 lectins).

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania.

BACKGROUND: Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. METHODS: 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. RESULTS: There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). CONCLUSIONS: Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184.

Evidence for mucin-like glycoproteins that tether sporozoites of Cryptosporidium parvum to the inner surface of the oocyst wall.

Cryptosporidium parvum oocysts, which are spread by the fecal-oral route, have a single, multilayered wall that surrounds four sporozoites, the invasive form. The C. parvum oocyst wall is labeled by the Maclura pomifera agglutinin (MPA), which binds GalNAc, and the C. parvum wall contains at least two unique proteins (Cryptosporidium oocyst wall protein 1 [COWP1] and COWP8) identified by monoclonal antibodies. C. parvum sporozoites have on their surface multiple mucin-like glycoproteins with Ser- and Thr-rich repeats (e.g., gp40 and gp900). Here we used ruthenium red staining and electron microscopy to demonstrate fibrils, which appear to attach or tether sporozoites to the inner surface of the C. parvum oocyst wall. When disconnected from the sporozoites, some of these fibrillar tethers appear to collapse into globules on the inner surface of oocyst walls. The most abundant proteins of purified oocyst walls, which are missing the tethers and outer veil, were COWP1, COWP6, and COWP8, while COWP2, COWP3, and COWP4 were present in trace amounts. In contrast, MPA affinity-purified glycoproteins from C. parvum oocysts, which are composed of walls and sporozoites, included previously identified mucin-like glycoproteins, a GalNAc-binding lectin, a Ser protease inhibitor, and several novel glycoproteins (C. parvum MPA affinity-purified glycoprotein 1 [CpMPA1] to CpMPA4). By immunoelectron microscopy (immuno-EM), we localized mucin-like glycoproteins (gp40 and gp900) to the ruthenium red-stained fibrils on the inner surface wall of oocysts, while antibodies to the O-linked GalNAc on glycoproteins were localized to the globules. These results suggest that mucin-like glycoproteins, which are associated with the sporozoite surface, may contribute to fibrils and/or globules that tether sporozoites to the inner surface of oocyst walls.

Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries.

BACKGROUND: There is a significant increase in survival for HIV-infected children who have early access to diagnosis and treatment. The goal of this multi-country review was to examine when and where HIV-exposed infants and children are being diagnosed, and whether the EID service is being maximally utilized to improve health outcomes for HIV-exposed children. METHODS: In four countries across Africa and Asia existing documents and data were reviewed and key informant interviews were conducted. EID testing data was gathered from the central testing laboratories and was then complemented by health facility level data extraction which took place using a standardized and validated questionnaire RESULTS: In the four countries reviewed from 2006 to 2009 EID sample volumes rose dramatically to an average of >100 samples per quarter in Cambodia and Senegal, >7,000 samples per quarter in Uganda, and >2,000 samples per quarter in Namibia. Geographic coverage of sites also rapidly expanded to 525 sites in Uganda, 205 in Namibia, 48 in Senegal, and 26 in Cambodia in 2009. However, only a small proportion of testing was done at lower-level health facilities: in Uganda Health Center IIs and IIIs comprised 47% of the EID collection sites, but only 11% of the total tests, and in Namibia 15% of EID sites collected >93% of all samples. In all countries except for Namibia, more than 50% of the EID testing was done after 2 months of age. Few sites had robust referral mechanisms between EID and ART. In a sub-sample of children, we noted significant attrition of infants along the continuum of care post testing. Only 22% (Senegal), 37% (Uganda), and 38% (Cambodia) of infants testing positive by PCR were subsequently initiated onto treatment. In Namibia, which had almost universal EID coverage, more than 70% of PCR-positive infants initiated ART in 2008. CONCLUSIONS: While EID testing has expanded dramatically, a large proportion of PCR- positive infants are initiated on treatment. As EID services continue to scale-up, more programmatic attention and support is needed to retain HIV-exposed infants in care and ensure that those testing positive initiate treatment in a timely manner. Namibia's experience demonstrates that it is feasible for a rural, low-income country to achieve high national coverage of infant testing and treatment.

Primary healthcare and child and maternal health in the Middle East and North Africa (MENA): A retrospective analysis of 29 national survey data from 13 countries.

The objective of this paper is three-fold: (i) to analyse the coverage and equity of access to selected maternal and child healthcare interventions, particularly those delivered in Primary Healthcare (PHC) setting; (ii) to analyse the main drivers of inequitable access to selected interventions; and (iii) to synthesise and compare the results across the Middle East and North Africa (MENA) region as well as over time. We analysed data for five key maternal and child healthcare interventions from 29 national surveys (DHS and MICS) covering 13 MENA countries and spanning a period of almost 20 years (2000-2018). We calculated coverage indicators, concentration indices (CI) and decomposition of CIs according to standard definitions. We synthetized the results by country groups based on their human development index (HDI). Over time and among countries that started from a lower base, there has been an improvement in coverage and equity of selected interventions (four ante-natal care visits and skilled birth assistance). When considering the place of skilled delivery, there is a clear rich-poor divide, with women from richer wealth quintiles gravitating toward private healthcare facilities and those from poorer wealth quintiles toward public ones. While most of the care-seeking for common child illnesses occurs in PHC facilities, a fraction (20-30 percent) of care-seeking takes place in secondary healthcare facilities. PHC has played a role in improving coverage and equity of access in key maternal and child health interventions in the wider MENA region. Better integration of care, strengthening and improving the PHC network could increase the use of cost-effective interventions, which are key to improving maternal and child health.

Outdoor activity and myopia progression in children: A follow-up study using mixed-effects model.

PURPOSE: The purpose of this study was to determine the influence of outdoor activity on myopia progression. METHODS: It was a hospital-based longitudinal prospective observational study. Children between 7 and 14 years of age with a myopia of - 0.5 D or worse were included. Myopia progression was evaluated by cycloplegic refraction, every 6 months for 18 months. Parents were asked to record the daily outdoor activity of the child in hours per day at school and at home during weekdays and at weekends separately, based on which the daily outdoor activity score was calculated. The independent variables measured included age and gender of the participant, degree of myopia, and the daily outdoor activity score. Progression of myopia was defined as an increase in the spherical equivalent (SE) over 18 months. The magnitude of the association was determined by two mixed-effects models. RESULTS: A total of 495 participants (250 males and 245 females) completed three visits during the study period. On taking age groups and paired observations as a random effect and adding SE at the last visit as the random slope in Model 1, each unit increase in outdoor activity had a negative effect on change in SE of - 0.01 (-0.02 to 0.00; P = 0.045). The same inverse relationship between outdoor activity and absolute SE as - 0.06 (-0.07 to - 0.03; P < 0.001) is estimated in Model 2. CONCLUSION: The study demonstrates a statistically significant inverse relationship between outdoor activity and myopia.