Advances in molecular pathogenesis of hidradenitis suppurativa: Dysregulated keratins and ECM signaling.

Hidradenitis suppurativa (HS) is characterized by deep-seated, highly inflamed, and painful lumps/abscesses, fistulae, and sinus tracts that grow extensively deep in the dermis and are highly immunogenic in nature. In about one-third of the HS patients there is strong evidence for the role of γ-secretase mutations along with dysregulated Notch signaling. However, the contribution of dysregulated Notch signaling in HS pathogenesis in relation to hair follicle alterations and hyper-activation of the immune system remains undefined. A genome-wide association study (GWAS), proteomic data and functional investigations of identified sequence variants in HS pathology are not fully revealing. The disease initiation or progression may involve bacterial infection besides intrinsic functional defects in keratinocytes, which may be key to further exacerbate immune cell infiltration and cytokine production in and around the lesional tissue. The absence of a suitable animal model that could fully recapitulate the pathogenesis of HS is a major impediment for proper understanding the underlying mechanisms and development of effective treatments. The presence of extracellular matrix (ECM) degradation products along with dysregulation in keratinocytes and, dermal fibroblasts ultimately affect immune regulation and are various components of HS pathogenesis. Bacterial infection further exacerbates the complexity of the disease progression. While anti-TNFα therapy shows partial efficacy, treatment to cure HS is absent. Multiple clinical trials targeting various cytokines, complement C5a and ECM products are in progress. This review provides state-of-the-art information on these aspects with a focus on dysregulated keratinocyte and immune cells; and role of ECM, and Keratin functions in this regard.

Mini-Scleral Lens: An Effective Mode of Visual Rehabilitation in Eyes With Resolved Hydrops.

OBJECTIVES: To evaluate the visual outcome of mini-scleral contact lenses (MSLs) in keratoconus following the resolution of acute hydrops. METHODS: This was a prospective observational case series of patients of healed hydrops in keratoconus fitted with an MSL (Keracare, Acculens, Lakewood, CO) who were managed for acute hydrops medically or surgically at least 3 months prior. Uncorrected visual acuity, best spectacles-corrected visual acuity, best lens-corrected visual acuity, topographic indices, keratometric indices, contact lens parameters, and ocular aberrometric changes were evaluated. All patients were followed up for at least 3 months. RESULTS: Eighteen eyes of 17 patients were included in the analysis. The mean post-hydrops topographic values of the eyes included flat keratometric value (K1) 64.93±10.88 (range 44.30-93.40) diopters (D), steep keratometric value (K2) 70.41±10.92 D (range 45.8-98.6 D), and Kmax of 79.53±17.73 D (range 50-130.2). The final mini-scleral lens's mean dioptric power was -8.56±3.96 D (range -18 to -4). Visual acuity significantly improved from post-hydrops resolution uncorrected visual acuity of 1.5±0.71 logMAR to 0.79±0.18 logMAR best spectacles-corrected visual acuity to 0.27±0.01 logMAR best lens-corrected visual acuity (P-value <0.0001). Similarly, there was considerable improvement in corneal aberrometric values after wearing an MSL. At the 3-month follow-up, 15 patients (16 eyes) were compliant to contact lens use with a minimum of 6 to 8 hr daily while two patients (2 eyes) were poorly compliant. CONCLUSIONS: A MSL is a valuable option for visual rehabilitation in keratoconus following the resolution of acute hydrops.

Epigenetic regulation in the pathogenesis of non-melanoma skin cancer.

Understanding of cancer with the help of ever-expanding cutting edge technological tools and bioinformatics is revolutionizing modern cancer research by broadening the space of discovery window of various genomic and epigenomic processes. Genomics data integrated with multi-omics layering have advanced cancer research. Uncovering such layers of genetic mutations/modifications, epigenetic regulation and their role in the complex pathophysiology of cancer progression could lead to novel therapeutic interventions. Although a plethora of literature is available in public domain defining the role of various tumor driver gene mutations, understanding of epigenetic regulation of cancer is still emerging. This review focuses on epigenetic regulation association with the pathogenesis of non-melanoma skin cancer (NMSC). NMSC has higher prevalence in Caucasian populations compared to other races. Due to lack of proper reporting to cancer registries, the incidence rates for NMSC worldwide cannot be accurately estimated. However, this is the most common neoplasm in humans, and millions of new cases per year are reported in the United States alone. In organ transplant recipients, the incidence of NMSC particularly of squamous cell carcinoma (SCC) is very high and these SCCs frequently become metastatic and lethal. Understanding of solar ultraviolet (UV) light-induced damage and impaired DNA repair process leading to DNA mutations and nuclear instability provide an insight into the pathogenesis of metastatic neoplasm. This review discusses the recent advances in the field of epigenetics of NMSCs. Particularly, the role of DNA methylation, histone hyperacetylation and non-coding RNA such as long-chain noncoding (lnc) RNAs, circular RNAs and miRNA in the disease progression are summarized.

Clinical Profile and Treatment Outcomes of Patients With Acremonium Species Positive Keratitis Managed in a Tertiary Eye Care Center.

PURPOSE: To report the clinical profile and treatment outcomes of patients with culture-positive Acremonium keratitis. METHODS: This is a retrospective observational study. Medical records of all patients treated in a tertiary eye hospital for culture positive infective keratitis from March 2016 to February 2021 were screened, of which those positive for Acremonium species on fungal culture were reviewed. Demographic details, clinical presentation, clinical course, treatment given, total follow-up duration, time taken for ulcer to heal, scar size, and final visual acuity in the last follow-up were recorded. RESULTS: Fifty three cases of fungal keratitis caused by Acremonium species were identified, 22 females and 31 males, with average age of 46.39±18.64 years. The mean duration of symptoms being 54.47±50 days. Only five patients had a history of trauma with vegetative matter. Clinical presentation of patients showed a large number of variations, with 2 patients presenting as peripheral ulcerative keratitis and 1 with epithelial plaque. The mean visual acuity of patients at presentation was 2.43±0.46 logMAR units. Thirty-three of 53 patients presented with perforated corneal ulcer and underwent penetrating keratoplasty; 20 patients were medically managed on topical voriconazole 1%, natamycin 5%, and oral voriconazole. The mean duration of healing of epithelial defect was 95±60.62 days (range 60-165 days). CONCLUSION: Acremonium keratitis has a long and indolent course. A prolonged combination therapy of natamycin and voriconazole seems to be effective in the management. A delay in the diagnosis of Acremonium keratitis often leads to clinical worsening requiring keratoplasty.

Long-term Outcomes of Fibrin Glue-Assisted Intrascleral Haptic Fixation of Posterior Chamber Intraocular Lenses in Children.

OBJECTIVES: To evaluate the long-term outcomes of intrascleral haptic fixation of posterior chamber intraocular lens (PCIOL) with fibrin glue in children. METHODS: This is a retrospective case study conducted in a tertiary eye institute in North India. A total of 118 eyes of 82 children who underwent glued intrascleral haptic fixation of PCIOLs were retrospectively analyzed. Detailed analysis of the indication for surgery and ocular and systemic associations was performed. The outcome measures included intraoperative complications, final visual and refractive outcomes, and postoperative complications. RESULTS: The mean age of the patients was 10.16±3.94 years. Fifty-one patients (62.2%) were male and 31 (37.8%) were female. The mean follow-up period was 31.28±13.22 months. The mean preoperative corrected distance visual acuity was 1.18±0.63 Logarithm of Mean angle of resolution (logMAR) which improved to 0.60±0.58 logMAR postoperatively at 6 weeks (P<0.001). The mean preoperative and 6 weeks postoperative endothelial cell density were 3,176.08±318.6 and 2,936±289.9 cells/mm2, respectively (P=0.23). In the immediate postoperative period, corneal edema (19 eyes; 16.1%), decentered IOL/tilt (3 eyes; 2.54%), vitreous hemorrhage (3 eyes; 2.54%), optic capture (4 eyes; 3.38%), and hypotony (2 eyes; 1.69%) were seen. In the late postoperative period (>6 weeks), retinal detachment was observed in two eyes that had associated Marfan syndrome. Cystoid macular edema was seen in four eyes (3.38%), and glaucoma was seen in five eyes (4.23%). CONCLUSIONS: Fibrin glue-assisted intrascleral haptic fixation of a PCIOL is a safe and effective method to manage aphakia with inadequate capsular support in children.

Evaluation of Visual Outcome of 2 Phakic Posterior Chamber Implantable Lenses in High Myopia: A Comparative Study.

PURPOSE: To evaluate and compare the visual outcomes of two phakic intraocular lenses in high myopia. METHODS: A prospective comparative study was undertaken on 50 eyes of 26 patients {age ≥21 years and divided into two groups (implantable collamer lens [ICL] V4c, n=25 eyes and refractive implantable lens [RIL], n=25 eyes)}. Patients were evaluated for uncorrected distance visual acuity (UCVA), best-corrected distance visual acuity, manifest refractive spherical equivalent (MRSE), contrast sensitivity, intraocular pressure, dilated fundus examination, trabecular-iris angle (TIA), anterior chamber depth, horizontal white-to-white diameter, wavefront aberrometry, and endothelial cell (EC) count. All patients were followed up until 6 months and additionally evaluated for anterior chamber inflammation, cataract, and lens vault. RESULTS: The baseline parameters (UCVA, MRSE, and EC count) and postoperative improvement in UCVA, contrast sensitivity, MRSE, EC loss, safety index, and efficacy index were comparable between both the lenses. The improvement in aberrometric profile was significantly better in the ICL group. The mean postoperative vault was higher in RIL group (434.88±162.48 µm vs. 547.24±159.83 µm, P=0.0173); however, the vault was within normal range in both the groups. The decrease in mean TIA was significantly higher in RIL group (8.58 vs. 13.45 µm, P=0.0073). CONCLUSION: Acrylic phakic lens can be considered as a suitable alternative to collamer lens for refractive correction of high myopia. The collamer lenses showed slight superiority in some qualitative visual parameters; however, collamer lenses do not present with subjective complaints in the patients.

Nurses' knowledge of and attitude to nursing information systems.

BACKGROUND: The use of a nursing information system (NIS) provides significant benefit to the nurses in the management of real-time patient data and contributes to improving the operational effectiveness of nursing services. AIM: To assess the knowledge of, attitude towards and use of an NIS. METHODS: A prospective cross-sectional study was carried out among 230 hospital nurses in India, using a validated questionnaire including demographic characteristics, and questions on knowledge of, attitude towards and use of an NIS. FINDINGS: The study found that more than 70% of nurses had good computer skills and knowledge about the information system. About 75% of the nurses reported that the NIS could be a tool to support them in improving patient care, and medical documentation, although 42% claimed that the use of NIS depersonalises nursing care. Seventy-one per cent of the nurses expressed the need for formal education and training on using an NIS during and after their nursing education. CONCLUSION: Training and demonstration of NISs during nurse education would improve nurses' knowledge, build confidence and positive attitudes, and enhance the acceptability and sustainability of NISs in healthcare settings.

Evaluation of a training program for life skills education and financial literacy to community health workers in India: a quasi-experimental study.

BACKGROUND: Accredited Social Health Activists (ASHA) are community health workers responsible for improving the health status of people by facilitating their access to healthcare services. The life skills of ASHA are known to be effective in negotiating behaviour change in the community; however, there has been a meagre focus towards improving them. Considering this gap, we adopted a comprehensive training program, known as Personal Advancement and Career Enhancement (P.A.C.E.), to empower ASHAs on life skills and financial literacy. The present study intends to assess the training program in two districts of Uttar Pradesh, India, by examining changes in knowledge, perceptions, and practices of ASHAs about life skills and financial literacy. METHODS: We conducted a quasi-experimental, non-randomized, controlled study with pre-and post-test assessments. Data were collected on socio-demographic characteristics, knowledge, and practices related to life skills (communication skills, self-confidence, problem-solving and decision-making skills, time and stress management skills) and financial literacy. Additionally, change perceptions on gender-, life skills-, and savings-related practices at the personal, community, and workplace levels were assessed in the intervention group. Factor analysis was performed to obtain the change patterns by assessing the degree to which the four life skills, financial literacy, and change perceptions on practices were correlated. A general linear regression model was performed to assess associations among change pattern scores and socio-demographic variables. RESULTS: We analyzed the data of 171 ASHAs (intervention group:86 and control group:85). There was a significant improvement in the average post-test scores of all the life skills and financial literacy in the intervention group (p < 0.001). Three distinct change patterns were found post-training in the intervention group. Factor 1 (high loadings for change perceptions on practices) was positively associated with ASHAs aged 38 and above and with experience of ≤12 years. On the contrary, the change in financial literacy and self-confidence scores was common among ASHAs with more than 12 years of experience. CONCLUSIONS: The P.A.C.E training program was found effective in improving the life skills and financial literacy of ASHAs in India.

Assessment of posture-induced cyclotorsion during cataract surgery using the Verion image-guided system.

BACKGROUND: The purpose of this prospective observational study is to analyse posture-induced cyclotorsion in eyes undergoing conventional phacoemulsification with toric intraocular lens (IOL) implantation and femtolaser-assisted cataract surgery (FLACS) using the Verion image-guided system. METHODS: Cyclotorsion was assessed in patients who underwent conventional phacoemulsification with toric IOL implantation and FLACS between June 2017 and November 2017 with registration of iris architecture, limbal and bulbar conjunctival blood vessels acquired preoperatively using the Verion Reference Unit (the patient in sitting position) and intraoperatively under the microscope using the digital marker of the Verion image-guided system with the patient in supine position. RESULTS: Forty-four eyes of 30 patients (21 men and 9 women) were included with the mean age of 56.5 ± 17.1 (range, 19-89; median, 62) years. The mean cyclotorsion induced by change in posture from sitting to supine position was 5.84 ± 3.25° (range, 1-17; median, 5). Overall, clockwise (CW) rotation (59.1%) was noted to be more common than counter clockwise (CCW) rotation (40.9%). Furthermore, CW rotation was more common in men than in women, and CCW rotation was significantly more common in women. Patients who underwent bilateral sequential cataract surgery show similar cyclorotation (CW or CCW) in both eyes more often than mixed rotation (85.7% vs 14.3%). CONCLUSION: Significant cyclotorsion can occur in supine position during cataract surgery. Accurate assessment of the amount and direction of cyclotorsion aids in appropriate alignment of the toric IOL for optimal visual outcomes.

Relationship between mid-upper arm circumference and BMI for identifying maternal wasting and severe wasting: a cross-sectional assessment.

OBJECTIVE: To assess the strength of correlation and agreement between mid-upper arm circumference (MUAC) and BMI, and determine suitable MUAC cut-offs, to detect wasting and severe wasting among non-pregnant adult women in India. DESIGN: Cross-sectional studies were conducted in five high-burden pockets of four Indian states. SETTING: Prevalence of malnutrition among women and children is very high in these pockets and the government plans to implement community-based pilot projects to address malnutrition in these areas. PARTICIPANTS: Anthropometric measurements were carried out on 1716 women with children <5 years of age. However, analyses were conducted on 1538 non-pregnant adult women. RESULTS: The results showed a strong correlation between MUAC and BMI in the non-pregnant women, with correlation coefficient of 0·860 (95 % CI 0·831, 0·883; P < 0·001). Cohen's κ of 0·812 and 0·884 also showed good agreement between MUAC and BMI in identifying maternal wasting and severe wasting, respectively. The univariate regression model between MUAC and BMI explained 0·734 or 73 % of the variation in BMI. The MUAC cut-offs for wasting (BMI < 18·5 kg/m2) and severe wasting (BMI < 16·0 kg/m2) were calculated as 232 and 214·5 mm, respectively. CONCLUSIONS: MUAC is a strong predictor of maternal BMI among non-pregnant women with children <5 years in high-burden pockets of four Indian states. In a resource-constrained setting where BMI may not be feasible, the MUAC cut-offs could reliably be used to screen wasting and severe wasting in non-pregnant women for providing appropriate care.

Effects of participatory learning and action with women's groups, counselling through home visits and crèches on undernutrition among children under three years in eastern India: a quasi-experimental study.

BACKGROUND: India faces a high burden of child undernutrition. We evaluated the effects of two community strategies to reduce undernutrition among children under 3 years in rural Jharkhand and Odisha, eastern India: (1) monthly Participatory Learning and Action (PLA) meetings with women's groups followed by home visits; (2) crèches for children aged 6 months to 3 years combined with monthly PLA meetings and home visits. METHODS: We tested these strategies in a non-randomised, controlled study with baseline and endline cross-sectional surveys. We purposively selected five blocks of Jharkhand and Odisha, and divided each block into three areas. Area 1 served as control. In Area 2, trained local female workers facilitated PLA meetings and offered counselling to mothers of children under three at home. In Area 3, workers facilitated PLA meetings, did home visits, and crèches with food and growth monitoring were opened for children aged 6 months to 3 years. We did a census across all study areas and randomly sampled 4668 children under three and their mothers for interview and anthropometry at baseline and endline. The evaluation's primary outcome was wasting among children under three in areas 2 and 3 compared with area 1, adjusted for baseline differences between areas. Other outcomes included underweight, stunting, preventive and care-seeking practices for children. RESULTS: We interviewed 83% (3868/4668) of mothers of children under three sampled at baseline, and 76% (3563/4668) at endline. In area 2 (PLA and home visits), wasting among children under three was reduced by 34% (adjusted Odds Ratio [aOR]: 0.66, 95%: 0.51-0.88) and underweight by 25% (aOR: 0.75, 95% CI: 0.59-0.95), with no change in stunting (aOR: 1.23, 95% CI: 0.96-1.57). In area 3, (PLA, home visits, crèches), wasting was reduced by 27% (aOR: 0.73, 95% CI: 0.55-0.97), underweight by 40% (aOR: 0.60, 95% CI: 0.47-0.75), and stunting by 27% (aOR: 0.73, 95% CI: 0.57-0.93). CONCLUSIONS: Crèches, PLA meetings and home visits reduced undernutrition among children under three in rural eastern India. These interventions could be scaled up through government plans to strengthen home visits and community mobilisation with Accredited Social Health Activists, and through efforts to promote crèches. TRIAL REGISTRATION: The evaluation was registered retrospectively with Current Controlled Trials as ISCRTN89911047 on 30/01/2019.

B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis.

Sphingosine-1-phosphate (S1P) helps mediate lymphocyte egress from lymph nodes, yet many mechanistic questions remain. Here, we show the presence of B lymphocyte egress sites located in the lymph node cortex close to lymph node follicles. B cells exited lymph nodes by squeezing through apparent portals in the lymphatic endothelium of these sinusoids. Treatment with the S1P receptor agonist FTY720 emptied the cortical sinusoids of lymphocytes, blocked lymphatic endothelial penetration, and displaced B lymphocytes into the T cell zone. S1pr3(-/-) B cells, which lack chemoattractant responses to S1P, transited lymph nodes normally, whereas Gnai2(-/-) B cells, which have impaired responses to chemokines and S1P, transited more rapidly than did wild-type cells. This study identifies a major site of B lymphocyte lymph node egress, shows that FTY720 treatment blocks passage through the cortical lymphatic endothelium, and argues against a functional role for S1P chemotaxis in B lymphocyte egress.

The perilipin-like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy-inducing conditions.

Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one-third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin-1 and was upregulated in Mtb dormancy. We generated a ppe15 gene-disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three-dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild-type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin-1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG -containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.

Economic evaluation of participatory learning and action with women's groups facilitated by Accredited Social Health Activists to improve birth outcomes in rural eastern India.

BACKGROUND: Neonatal mortality remains unacceptably high in many low and middle-income countries, including India. A community mobilisation intervention using participatory learning and action with women's groups facilitated by Accredited Social Health Activists (ASHAs) was conducted to improve maternal and newborn health. The intervention was evaluated through a cluster-randomised controlled trial conducted in Jharkhand and Odisha, eastern India. This aims to assess the cost-effectiveness this intervention. METHODS: Costs were estimated from the provider's perspective and calculated separately for the women's group intervention and for activities to strengthen Village Health Sanitation and Nutrition Committees (VHNSC) conducted in all trial areas. Costs were estimated at 2017 prices and converted to US dollar (USD). The incremental cost-effectiveness ratio (ICER) was calculated with respect to a do-nothing alternative and compared with the WHO thresholds for cost-effective interventions. ICERs were calculated for cases of neonatal mortality and disability-adjusted life years (DALYs) averted. RESULTS: The incremental cost of the intervention was USD 83 per averted DALY (USD 99 inclusive of VHSNC strengthening costs), and the incremental cost per newborn death averted was USD 2545 (USD 3046 inclusive of VHSNC strengthening costs). The intervention was highly cost-effective according to WHO threshold, as the cost per life year saved or DALY averted was less than India's Gross Domestic Product (GDP) per capita. The robustness of the findings to assumptions was tested using a series of one-way sensitivity analyses. The sensitivity analysis does not change the conclusion that the intervention is highly cost-effective. CONCLUSION: Participatory learning and action with women's groups facilitated by ASHAs was highly cost-effective to reduce neonatal mortality in rural settings with low literacy levels and high neonatal mortality rates. This approach could effectively complement facility-based care in India and can be scaled up in comparable high mortality settings.

Comparative Evaluation of Use of 400-µm and 350-µm Microkeratome Head to Prepare Donor Tissue in Cases of Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To compare the outcomes of 400-µm microkeratome head with 350-µm microkeratome head Descemet stripping automated endothelial keratoplasty (DSAEK) in a prospective comparative study. METHODS: Twenty cases of pseudophakic bullous keratopathy were randomly allocated into two groups. Group 1 underwent slow, single-pass 400-µm microkeratome head, whereas group 2 underwent the standard technique of DSAEK using a 350-µm microkeratome head. The primary outcome measures were best-corrected visual acuity (BCVA) at 6 months. RESULTS: Groups were comparable in baseline characteristics. The mean central graft thickness (GT) at 6 months in group 1 was significantly thinner than group 2 (90.44±28.67 vs. 165.60±62.74 µm; P=0.003). The BCVA and contrast sensitivity were significantly better in group 1 than in group 2 (BCVA: 0.34±0.15 vs. 0.53±0.19 logMAR units, P=0.02; contrast sensitivity: 1.48±0.13 vs. 1.06±0.22, P=0.001). A significant correlation was found between both postoperative BCVA and contrast sensitivity, with the postoperative GT using Spearman rho correlation analysis (R=0.534, P=0.01 for BCVA and R=-0.522, P=0.02 for contrast sensitivity). The percentage endothelial cell loss was comparable between the 2 groups at the last follow-up (P=0.3). No major complications were observed during the study period. CONCLUSIONS: The use of a 400-µm microkeratome head instead of 350-µm head can improve the visual outcomes in DSAEK without increasing the risk of complications. The thickness of the DSAEK graft can affect the visual acuity and contrast sensitivity.

Transscleral Suture-Fixated Versus Intrascleral Haptic-Fixated Intraocular Lens: A Comparative Study.

PURPOSE: To compare the clinical outcomes between sutured transscleral-fixated and intrascleral haptic-fixated posterior chamber intraocular lens (IOL). SETTING: Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi. DESIGN: A comparative case series. METHODS: Forty eyes of 40 patients were included; 20 in each group. Patients in group 1 underwent sutured transscleral-fixated IOL and those in group 2 underwent intrascleral haptic-fixated IOL augmented by fibrin glue. Parameters evaluated were uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), IOL tilt on ultrasound biomicroscopy (UBM), and pseudophakodonesis on slitlamp and UBM. RESULTS: The most common cause of aphakia was complicated cataract surgery (50%). The mean preoperative UCVA in logarithm of minimum angle of resolution (logMAR) was 1.59±0.24 and 1.63±0.26 in group 1 and 2, respectively (P=0.45). There was significant improvement in UCVA in both groups (P=0.001) at 6 months (group 1: 0.33±0.17; group 2: 0.22±0.10); the improvement being greater in group 2 (P<0.05). Mean percentage endothelial cell loss and IOP change were comparable. Mean CMT (µm) was 250.95±23.98 and 225.85±21.13 in group 1 and 2, respectively (P=0.009). Pseudophakodonesis was more in group 1 as assessed on slitlamp (P=0.037) and as assessed on UBM (P=0.046). Macular edema was the most common complication seen more in group 1. CONCLUSIONS: Intrascleral haptic-fixated IOL provides more stable fixation, better visual outcome, and lesser complication in comparison with sutured transscleral-fixated IOL.

Mce4A protein of Mycobacterium tuberculosis induces pro inflammatory cytokine response leading to macrophage apoptosis in a TNF-α dependent manner.

Mycobacterium tuberculosis subverts the host immune response through numerous immune-evasion strategies. Apoptosis has been identified as one such mechanism and has been well studied in M. tuberculosis infection. Here, we demonstrate that the Mce4A protein of mce4 operon is involved in the induction of host cell apoptosis. Earlier we have shown that the Mce4A was required for the invasion and survival of M. tuberculosis. In this report we present evidence to establish a role for Mce4A in the modulation of THP-1 cell survival. Recombinant Mce4A was expressed and purified from Escherichia coli as inclusion bodies and then refolded. Viability of THP-1 cells decreased in a dose-dependent manner when treated with Mce4A. The secretion of pro-inflammatory cytokines like tumor necrosis factor (TNF-α) or interferon gamma (IFN-γ), and enhanced nitric oxide release was observed when the THP-1 cells, were treated with Mce4A protein. The Mce4A induced apoptosis of the THP-1 cells was TNF-α dependent since blocking with anti TNF-α antibody abrogated this phenomenon. Collectively, these data suggest that Mce4A can induce the THP-1 cells to undergo apoptosis which primarily follows a TNF- α dependent pathway.

Social determinants of inequities in under-nutrition (weight-for-age) among under-5 children: a cross sectional study in Gumla district of Jharkhand, India.

BACKGROUND: Jharkhand, a state with substantial tribal population in Eastern India has very high rate of undernutrition. The study tries to understand the social determinants of inequities in under-nutrition (weight-for-age) among children aged less than 5 years, in Gumla District of the State. METHODS: Cross sectional study of 1070 children from 32 villages of 4 Blocks of Gumla District. RESULTS: 54.3 % (95 % CI 51.3-57.3) children were found to be underweight (less than -2SD), with insignificant difference between girls and boys. Multivariate analysis showed that poverty was the single most important predictor of undernutrition, where a child from the poorest quintile was 70 % more likely to be underweight (aOR 1.70, CI 1.13-2.57), compared to one from the least poor group (Quintile 5). While the difference in weight-for-age status between Scheduled Tribes and "OBC and other communities" was non-significant (95 % OR 1.12, CI 0.88-1.42) in the study context; community disaggregated data revealed that there were large variations within the tribal community, and numerically smaller communities also ranked lower in wealth, and their children showed poorer nutritional status. Other factors like maternal education beyond matriculation level also had some bearing. Bivariate analysis showed that chances of a child being underweight (<-2SD) was 43 % more and being severely underweight (<-3SD) was 26 % more for mothers with less than 10 years of schooling compared to those who had attended school for more than 10 years. Educational attainment of mothers did not show any significant difference between tribal and non-tribal communities. CONCLUSION: Overall nutritional status of children in Gumla is very grim and calls for immediate interventions, with universal coverage. Risk was almost equal for both genders, and for tribal and non-tribal population, though within tribal communities, it was slightly higher for smaller tribal communities, calling for soft targeting. Comprehensive programme addressing poverty and higher education for girls would be important to overcome the structural barriers, and should be integral part of any intervention. The study highlights the importance of soft targeting vulnerable communities within the universal coverage of government programmes for better nutritional outcomes.

Are village health sanitation and nutrition committees fulfilling their roles for decentralised health planning and action? A mixed methods study from rural eastern India.

BACKGROUND: In India, Village Health Sanitation and Nutrition Committees (VHSNCs) are participatory community health forums, but there is little information about their composition, functioning and effectiveness. Our study examined VHSNCs as enablers of participatory action for community health in two rural districts in two states of eastern India - West Singhbhum in Jharkhand and Kendujhar, in Odisha. METHODS: We conducted a cross-sectional survey of 169 VHSNCs and ten qualitative focus group discussions with purposively selected better and poorer performing committees, across the two states. We analysed the quantitative data using descriptive statistics and the qualitative data using a Framework approach. RESULTS: We found that VHSNCs comprised equitable representation from vulnerable groups when they were formed. More than 75 % members were women. Almost all members belonged to socially disadvantaged classes. Less than 1 % members had received any training. Supervision of committees by district or block officials was rare. Their work focused largely on strengthening village sanitation, conducting health awareness activities, and supporting medical treatment for ill or malnourished children and pregnant mothers. In reality, 62 % committees monitored community health workers, 6.5 % checked sub-centres and 2.4 % monitored drug availability with community health workers. Virtually none monitored data on malnutrition. Community health and nutrition workers acted as conveners and record keepers. Links with the community involved awareness generation and community monitoring of VHSNC activities. Key challenges included irregular meetings, members' limited understanding of their roles and responsibilities, restrictions on planning and fund utilisation, and weak linkages with the broader health system. CONCLUSIONS: Our study suggests that VHSNCs perform few of their specified functions for decentralized planning and action. If VHSNCs are to be instrumental in improving community health, sanitation and nutrition, they need education, mobilisation and monitoring for formal links with the wider health system.