Advance Teaching of Fundamentals of Homoeopathy (ATFH): redefining competency based approach

The curriculumin academic medicine is defined by writing effective Learning objectives (LO). LO iselaborated based on perceptions of unbiased written aspects,of course, the rationale in statements is explained and tested through the completion of educational activity. These are the foundations for defining the outcomes in building up strong educational policieswhich are instructionalaligned through predefined effective curriculum courseswith added mapped outcomes. This letter provides the ongoing aspect of the development of Homoeopathic education in India regulated by the National Commission for Homoeopathy for the subject course of Advance Teaching of Fundamentals of Homoeopathy (ATFH). The essential components for the ATFHsubject course with LO and outcome assessment is been discussed and would provide a new arena of academic research in building up rationale in the programed [Doctor of Homoeopathy(MD,(Hom).

A Cross-Country Network Analysis of Adolescent Resilience.

PURPOSE: In situations of adversity, young people draw on individual, relational, and contextual (community and cultural) resources to foster their resilience. Recent literature defines resilience as a capacity that is underpinned by a network of interrelated resources. Although empirical studies show evidence of the value of a network approach, little is known regarding how different country contexts influence which resources are most critical within a resource network and how resources interact for adolescent resilience. METHODS: Network analysis was conducted with data from studies that had used the Child and Youth Resilience Measure. Regularized partial correlation networks of 17 resources were estimated for 14 countries (Botswana, Canada, China, Colombia, Equatorial Guinea, India, Indonesia, Italy, Jordan, New Zealand, the Philippines, Romania, South Africa, and Syrian refugees living in Jordan). The sample size was 18,914 (mean age = 15.70 years, 48.8% female). RESULTS: We observed mostly positive associations between the resources of interest. The salience and strength of associations between resources varied by country. The most central resource across countries was having supportive caregivers during stressful times because this resource had the most and strongest positive associations with other resources. CONCLUSIONS: This study gives first empirical evidence from multiple countries that an interplay of social-ecological resources (such as individual skills, peer, caregiver and community support, and educational aspirations and opportunities) matter for adolescent resilience. Across countries, caregiver support appears to be most central for adolescent resilience. Future resilience interventions might apply this network approach to identify important, contextually relevant resources that likely foster additional resources.

Early Ophthalmic Changes in Macula Does Not Correlate with Visual Function.

PURPOSE: Early detection and treatment of age-related macular degeneration require a clear understanding of the early progress of the disease. The purpose of this study was to investigate whether minimal macular ophthalmoscopic changes corresponded to changes in visual function. METHODS: Color macular photos from a group of older subjects who were classified as grade 0 on AREDS simplified grading were further evaluated by a retinal specialist using 5x magnification for possible minimal macular anomalies. Group 0-A (N = 15) were defined as subjects with no visible macular anomalies while Group 0-B (N = 19) comprised subjects for whom minimal macular mottling, pigment changes or very small drusen (< 63 µm) were observed in the study eye. All subjects had best VA of 20/25 or better and had no evidence of other retinal diseases in the study eye. All subjects underwent a series of visual function tests such as standard ETDRS VA, low luminance ETDRS VA, Pelli-Robson contrast sensitivity, variable contrast flicker (VCF) sensitivity, and reading speed (words per minute, wpm) using both MNRead and low luminance reading on a tablet. RESULTS: There was no significant difference between the mean age between the two groups (74.8 ± 5.2 years for 0-A vs 74.5 ± 4.4 for 0-B, p = 0.82). None of the visual function tests identified any significant difference between the two groups. Mean ETDRS VA was 0.0 ± 0.11 for 0-A subjects and 0.08 ± 0.12 for 0-B (p = 0.063). Mean Pelli-Robson log contrast sensitivity was 1.75 ± 0.29 for 0-A and 1.78 ± 0.17 for the 0-B group (p = 0.73). VCF threshold was 0.47 ± 0.25 for 0-A and 0.43 ± 0.22 for 0-B (p = 0.64). Reading speed using MNRead was 214 ± 47.4 wpm for 0-A and 210 ± 64.7 for 0-B (p = 0.85). Low luminance tablet reading speed was 137 ± 71.8 wpm for 0-A and 151 ± 39.4 (0-B) (p = 0.49). CONCLUSION: A panel of psychophysical tests did not demonstrate significant differences between subjects with and without minimal macular changes.

Stigma toward mental illness among higher secondary school teachers in Puducherry, South India.

BACKGROUND: A majority of mental illness start during adolescent period, and teachers can be a major resource in provision of mental health services to them. Stigma is a major barrier between persons with mental illness and opportunities to recover. MATERIALS AND METHODS: Cross-sectional analytical study was conducted to assess the stigma toward mental illness and associated factors among higher secondary school teachers in Puducherry from April 2017 to March 2018. Multistage sampling was used to select 566 teachers from 46 schools. A part of the vignette-based "Mental Health Literacy Scale" portraying depression was used to assess stigma toward mental illness. Sociodemographic and work characteristics were also obtained. Data were analyzed using SPSS v16. To identify factors associated with stigma, bivariate analysis was done using Chi-square test and multivariate analysis using logistic regression. RESULTS: Among the teachers, 72.9% and 65.7% showed overall agreement to personal and perceived stigma, respectively, toward case in vignette. Teachers in lower age group [adjusted odds ratio (AOR): 4.6 (95% confidence interval (CI): 2.54-8.33)], male gender [AOR: 2.79 (95% CI: 1.85-4.24)], working in urban [AOR: 2.8 (95% CI: 1.91-4.15)], private schools [AOR: 2.58 (95% CI: 1.77-3.77)], and less teaching experience [AOR: 3.72 (95% CI: 2.4-5.88)] had significantly higher personal stigma. Similarly, lower age group [AOR: 4.6 (95% CI: 2.54-8.33)], male gender [AOR: 2.79 (95% CI: 1.85-4.24)], working in urban [AOR: 2.8 (95% CI: 1.91-4.15)] schools, and less teaching experience [AOR: 3.72 (95% CI: 2.4-5.88)] had significantly higher perceived stigma. CONCLUSION: About 70% teachers showed overall agreement to stigma toward the depressive case vignette. The significant factors influencing stigma were identified. This can act as a baseline to implementmental health training program for teachers therefore bringing an attitudinal shift to being positive toward the psychologically disturbed.

Aquaporins: Novel Targets for Age-Related Ocular Disorders.

Aquaporins (AQPs), a large family of membrane protein channels that facilitate transport of water and other small solutes, play important roles in physiological functions and human diseases. Up till now, 13 types of AQPs, numbered 0 through 12, have been identified in various mammalian tissues. Homologous genes for AQPs in amphibians, insects, and bacteria highlight the evolutionary conservation and, thus, the importance of these membrane channels. Many members of the AQP family are expressed in the eye. AQP1, which is a water-selective channel, is expressed in the anterior chamber (cornea, ciliary body, trabecular meshwork) and posterior chamber (retina and microvessels in choroid), controlling the fluid homeostasis in the eye. Mice knockout studies have indicated that AQP1 plays an important function in the eye by suggesting its role in aqueous humor dynamics and retina angiogenesis. This review will focus on the role of AQP1 as a novel target for ocular disorders such as glaucoma and age-related macular degeneration, and it will discuss challenges and advances in identifying modulators of AQP1 function that could be useful in clinical applications.

Targeted Intraceptor Nanoparticle for Neovascular Macular Degeneration: Preclinical Dose Optimization and Toxicology Assessment.

Neovascular age-related macular degeneration (AMD) is treated with anti-VEGF intravitreal injections, which can cause geographic atrophy, infection, and retinal fibrosis. To minimize these toxicities, we developed a nanoparticle delivery system for recombinant Flt23k intraceptor plasmid (RGD.Flt23k.NP) to suppress VEGF intracellularly within choroidal neovascular (CNV) lesions in a laser-induced CNV mouse model through intravenous administration. In the current study, we examined the efficacy and safety of RGD.Flt23k.NP in mice. The effect of various doses was determined using fluorescein angiography and optical coherence tomography to evaluate CNV leakage and volume. Efficacy was determined by the rate of inhibition of CNV volume at 2 weeks post-treatment. RGD.Flt23k.NP had peak efficacy at a dose range of 30-60 µg pFlt23k/mouse. Using the lower dose (30 µg pFlt23k/mouse), RGD.Flt23k.NP safety was determined both in single-dose groups and in repeat-dose (three times) groups by measuring body weight, organ weight, hemoglobin levels, complement C3 levels, and histological changes in vital organs. Neither toxicity nor inflammation from RGD.Flt23k.NP was detected. No side effect was detected on visual function. Thus, systemic RGD.Flt23k.NP may be an alternative to standard intravitreal anti-VEGF therapy for the treatment of neovascular AMD.

Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.

Aquaporins (AQPs) are a family of membrane proteins that function as channels facilitating water transport in response to osmotic gradients. These play critical roles in several normal physiological and pathological states and are targets for drug discovery. Selective inhibition of the AQP1 water channel may provide a new approach for the treatment of several disorders including ocular hypertension/glaucoma, congestive heart failure, brain swelling associated with a stroke, corneal and macular edema, pulmonary edema, and otic disorders such as hearing loss and vertigo. We developed a high-throughput assay to screen a library of compounds as potential AQP1 modulators by monitoring the fluorescence dequenching of entrapped calcein in a confluent layer of AQP1-overexpressing CHO cells that were exposed to a hypotonic shock. Promising candidates were tested in a Xenopus oocyte-swelling assay, which confirmed the identification of two lead classes of compounds belonging to aromatic sulfonamides and dihydrobenzofurans with IC50 s in the low micromolar range. These selected compounds directly inhibited water transport in AQP1-enriched stripped erythrocyte ghosts and in proteoliposomes reconstituted with purified AQP1. Validation of these lead compounds, by the three independent assays, establishes a set of attractive AQP1 blockers for developing novel, small-molecule functional modulators of human AQP1.

Status of eye donation awareness and its associated factors among adults in rural pondicherry.

INTRODUCTION: The value of anything is realized only when it is lost, one such thing is vision. Though all the causes of blindness can't be cured, corneal blindness can be reverted by corneal transplantation, for which a suitable donor cornea is required at right time. There is lack of awareness about eye donation among general population, so practice of eye donation is also lacking. Studies about awareness of eye donation among general population are lacking in rural India, keeping this in mind, present study was conducted. AIM: To determine the awareness about eye donation and its associated factors among adults in rural Pondicherry, India. MATERIALS AND METHODS: A cross-sectional study was conducted at Rural Health and Training Centre (RHTC) of Community Medicine department. Total 196 adults visiting to RHTC were interviewed after obtaining informed written consent. Data were collected by investigator using pre-designed and pre-tested questionnaire in local language (Tamil). The data were analyzed using epi info 7 software. Chi-square test was used for statistical significance between awareness and socio-demographic factors like age, sex, education, occupation, etc. Ethical permission was obtained before conducting the study. RESULT: Of 196 participants, 80.6% subjects were aware about eye donation. Education and occupation had significant association with awareness. Main source of information about eye donation was television (65.2%). The employed persons had significantly more awareness about the correct timing to donate eyes. Education and occupation were found to be the predictors for awareness about eye donation. CONCLUSION: Although the awareness is good in this population, the quantum of people pledged is very low. To make the dream of converting the awareness into pledging and procurement of eyes, the knowledge about eye donation is highly required.

Protein expression, biochemical pharmacology of signal transduction, and relation to intraocular pressure modulation by bradykinin B2 receptors in ciliary muscle.

PURPOSE: To examine the bradykinin (BK) B2-receptor system in human and monkey ciliary muscle (CM) using immunohistochemical techniques, and to pharmacologically characterize the associated biochemical signal transduction systems in human CM (h-CM) cells. BK-induced modulation of intraocular pressure (IOP) in pigmented Dutch-Belt rabbits and cynomolgus monkeys was also studied. METHODS: Previously published procedures were used throughout these studies. RESULTS: The human and monkey ciliary bodies expressed high levels of B2-receptor protein immunoreactivity. Various kinins differentially stimulated [Ca²âº](i) mobilization in primary h-CM cells (BK EC50=2.4±0.2 nM > Hyp³,ß-(2-thienyl)-Ala5,Tyr(Me)8-(®)-Arg9-BK (RMP-7) > Des-Arg9-BK EC50=4.2 µM [n=3-6]), and this was blocked by B2-selective antagonists, HOE-140 (IC50=1.4±0.1 nM) and WIN-63448 (IC50=174 nM). A phospholipase C inhibitor (U73122; 10-30 µM) and ethylene glycol tetraacetic acid (1-2 mM) abolished the BK-induced [Ca²âº](i) mobilization. Total prostaglandin (primarily PGE2) secretion stimulated by BK and other kinins in h-CM cells was attenuated by the cyclooxygenase inhibitors bromfenac and flurbiprofen, and by the B2-antagonists. BK and RMP-7 (100 nM) induced a twofold increase in extracellular signal-regulated kinase-1/2 phosphorylation, and BK (0.1-1 µM; at 24 h) caused a 1.4-3.1-fold increase in promatrix metalloproteinases-1-3 release. Topical ocular BK (100 µg) failed to alter IOP in cynomolgus monkeys. However, intravitreal injection of 50 µg of BK, but not Des-Arg9-BK, lowered IOP in rabbit eyes (22.9±7.3% and 37.0±5.6% at 5 h and 8 h post-injection; n=7-10). CONCLUSIONS: These studies have provided evidence of a functional endogenously expressed B2-receptor system in the CM that appears to be involved in modulating IOP.

Popular misconceptions regarding the diabetes management: where should we focus our attention?

BACKGROUND: Diabetes mellitus is a universal health problem with a global prevalence of 1.3%. India is known as the "Diabetes capital of the world" as it harbours the largest number of diabetes patients. There is lack of awareness about the existing interventions for preventing diabetes and for the management of the complications. One of the barriers in the way of seeking health care advice is the misconception about the disease, which revolves around all the aspects of diabetes, which include its prevention, control and treatment. OBJECTIVES: To determine the various misconceptions about the management of Diabetes mellitus in the study area.To find out the association of various misconceptions with the socio-demographic factors. MATERIAL AND METHODS: A cross-sectional study was conducted at the Urban Health Centre (UHC) Ariankuppam, Pondicherry. A total of 406 adult patients were interviewed. A pretested, semi-structured interview schedule was developed in the local language, and it was utilized to collect the data. The collected interview schedules were scrutinized for the accuracy of the information which was provided and for any lacunae. The compilation and analysis were carried out with the help of the Epi- Info software. The T test and the Chi-square test were used according to the distribution of the data, to see the associations of the different factors. RESULTS: The commonest misconceptions were "Diabetes can be cured by herbal treatment" (46.6%) and "Bitter foods reduce the elevated blood sugar levels" (46.6%). The misconception, "The treatment should be stopped if the diabetes is controlled for few months" significantly decreased with advancing age. There were no significant differences between females and males when the various misconceptions were compared. The commonest misconception among females was "Bitter foods reduce the elevated blood sugar levels" (49.4%) and among males, it was "Diabetes can be cured by herbal treatment" (47.9%). When the misconceptions were compared, it was found that there were significant differences between the subjects who belonged to different religions. CONCLUSION: The misconceptions regarding the diabetes management in the general population, irrespective of the education and particularly among the Muslim community, were widespread. A majority of these misconceptions were diet and drug related.

Impact of Janani Suraksha Yojana on institutional delivery rate and maternal morbidity and mortality: an observational study in India.

The Government of India initiated a cash incentive scheme--Janani Suraksha Yojana (JSY)--to promote institutional deliveries with an aim to reduce maternal mortality ratio (MMR). An observational study was conducted in a tertiary-care hospital of Madhya Pradesh, India, before and after implementation of JSY, with a sample of women presenting for institutional delivery. The objectives of this study were to: (i) determine the total number of institutional deliveries before and after implementation of JSY, (ii) determine the MMR, and (iii) compare factors associated with maternal mortality and morbidity. The data were analyzed for two years before implementation of JSY (2003-2005) and compared with two years following implementation of JSY (2005-2007). Overall, institutional deliveries increased by 42.6% after implementation, including those among rural, illiterate and primary-literate persons of lower socioeconomic strata. The main causes of maternal mortality were eclampsia, pre-eclampsia and severe anaemia both before and after implementation of JSY. Anaemia was the most common morbidity factor observed in this study. Among those who had institutional deliveries, there were significant increases in cases of eclampsia, pre-eclampsia, polyhydramnios, oligohydramnios, antepartum haemorrhage (APH), postpartum haemorrhage (PPH), and malaria after implementation of JSY. The scheme appeared to increase institutional delivery by at-risk mothers, which has the potential to reduce maternal morbidity and mortality, improve child survival, and ensure equity in maternal healthcare in India. The lessons from this study and other available sources should be utilized to improve the performance and implementation of JSY scheme in India.

Effect of elevated intracellular cAMP levels on actomyosin contraction in bovine trabecular meshwork cells.

PURPOSE: Elevated cAMP in the trabecular meshwork (TM) cells increases the aqueous humor outflow facility. The authors investigated the mechanisms by which elevated cAMP opposes the RhoA-Rho kinase pathway, leading to the relaxation of the actomyosin system in bovine TM cells. METHODS: Forskolin (Fsk) and rolipram were used to elevate cAMP levels. Changes in the phosphorylation of RhoA at Ser188 (a putative inhibitory site), the regulatory light chain of myosin (pMLC), and the regulatory subunit of myosin phosphatase (MYPT1) were determined by Western blot analysis. The actomyosin contraction was measured by collagen gel contraction (CGC) assay. The impact of cAMP on cell-matrix adhesion was followed by immunostaining of focal adhesion proteins and by electric cell-substrate impedance sensing. RESULTS: Elevated cAMP led to an increase in the phosphorylation of RhoA at Ser188, to the inhibition of endothelin-1 (ET-1)-induced activation of RhoA, and to the formation of stress fibers. The loss of pMLC along the stress fibers was comparable to that induced by Y-27632 (Rho kinase inhibitor). A concomitant reduction in both MYPT1 phosphorylation and pMLC was observed. Elevated cAMP also reduced (ET-1)-induced CGC and the cell-substrate resistance by >50%. CONCLUSIONS: In TM cells, elevated cAMP leads to the phosphorylation of RhoA at Ser188. Consequent inhibition of RhoA activity reduces the phosphorylation of MYPT1 at Thr853, leading to a reduction in MLC phosphorylation and actomyosin contraction. These actions, similar to those of the Rho kinase inhibitors, possibly underlie the reported increase in outflow facility in response to Fsk perfusion ex vivo.

Sutureless circumcision - An Indian experience.

CONTEXT: Traditionally, circumcision wounds are closed by absorbable sutures. However, certain alternative methods are also being utilized to overcome the shortcomings of the conventionally used method for circumcision wound closuring. In the current study, the use of tissue glue ((iso amyl 2-cyanoacrylate) has been compared with traditional suturing for the approximation of circumcision wounds. In our study, both the methods were found to be comparable with significantly less time consumed in glue group. AIMS: The purpose of the present study has been to compare directly cyanoacrylate as a better alternative to conventional suture material in terms of cosmetic result, time consumed and incidence of infection (comparative study). MATERIALS AND METHODS: The results of all the patients seen in outpatient department for circumcision were included in this study. The study was conducted from Aug 2009 to May 2010. The tissue glue (iso amyl 2-cyanoacrylate) was compared to sutures as a method of wound approximation in circumcision. RESULTS: Tissue glue group has been observed to have less wound inflammation, bleeding or hematoma rate and was cosmetically superior as compared to suture group; however, none of these findings could reach statistically significant level. The mean time taken for circumcision was 14.2 min (SD 2.42), when tissue glue was used for wound approximation. However, it was 24.4 min (SD 5.06) in case of the use of sutures. This difference was found as highly significant (P value < 0.001). However, regarding postoperative pain no significant reduction was observed when glue was used. CONCLUSIONS: This study showed that the use of tissue glue in comparison to sutures is having the following advantages: Cosmetically superiorLess time consuming All other parameters measured were nearly the same and statically insignificant.

Effect of down-regulation of aquaporins in human corneal endothelial and epithelial cell lines.

PURPOSE: The purpose of this study was to determine the effects of down-regulation of Aquaporin 1 (AQP1) and Aquaporin 5 (AQP5) on cell proliferation and migration in human corneal endothelial (HCEC) and human corneal epithelial (CEPI17) cell lines, respectively. METHODS: AQP1 and AQP5 were down regulated using siRNA following lipofectamine-mediated transfection in corneal endothelial and epithelial cells, respectively. Down-regulation was confirmed using RT-PCR, indirect immunofluorescence, and immunoblot analysis. Total internal reflection fluorescence (TIRF) microscopy was used to detect cell surface aquaporin expression. Cell proliferation was determined by SRB (sulfrodamine B) assay. Cell migration was determined by in vitro wound healing and migration assay. RESULTS: In HCEC cells, AQP1 was localized to the cytosol as well as cell membrane and its down-regulation resulted in decreased cell proliferation and migration with a significant decrease in phosphorylated ERK (pERK). In CEPI17 cells AQP5 protein expression was also localized to cytosol as well as cell membrane. AQP5 down-regulation resulted in an increase in proliferation and cell migration with no significant difference in pERK. CONCLUSIONS: AQP1 plays a role in HCEC proliferation and migration via the ERK signaling pathway and therefore may have significant implications in corneal endothelial dysfunction whereas; AQP5 may play an indirect role in human corneal epithelial cell proliferation and migration.

Changes in ocular aquaporin expression following optic nerve crush.

PURPOSE: Changes in the expression of water channels (aquaporins; AQP) have been reported in several diseases. However, such changes and mechanisms remain to be evaluated for retinal injury after optic nerve crush (ONC). This study was designed to analyze changes in the expression of AQP4 (water selective channel) and AQP9 (water and lactate channel) following ONC in the rat. METHODS: Rat retinal ganglion cells (RGCs) were retrogradely labeled by applying FluoroGold onto the left superior colliculus 1 week before ONC. Retinal injuries were induced by ONC unilaterally. Real-time PCR was used to measure changes in AQP4, AQP9, thy-1, Kir4.1 (K(+) channel), and beta-actin messages. Changes in AQP4, AQP9, Kir4.1, B cell lymphoma-x (bcl-xl), and glial fibrillary acidic protein (GFAP) expression were measured in total retinal extracts using western blotting. RESULTS: The number of RGCs labeled retrogradely from the superior colliculus was 2,090+/-85 cells/mm(2) in rats without any treatment, which decreased to 1,091+/-78 (47% loss) and 497+/-87 cells/mm(2) (76% loss) on days 7 and 14, respectively. AQP4, Kir4.1, and thy-1 protein levels decreased at days 2, 7, and 14, which paralleled a similar reduction in mRNA levels, with the exception of Kir4.1 mRNA at day 2 showing an apparent upregulation. In contrast, AQP9 mRNA and protein levels showed opposite changes to those observed for the latter targets. Whereas AQP9 mRNA increased at days 2 and 14, protein levels decreased at both time points. AQP9 mRNA decreased at day 7, while protein levels increased. GFAP (a marker of astrogliosis) remained upregulated at days 2, 7, and 14, while bcl-xl (anti-apoptotic) decreased. CONCLUSIONS: The reduced expression of AQP4 and Kir4.1 suggests dysfunctional ion coupling in retina following ONC and likely impaired retinal function. The sustained increase in GFAP indicates astrogliosis, while the decreased bcl-xl protein level suggests a commitment to cellular death, as clearly shown by the reduction in the RGC population and decreased thy-1 expression. Changes in AQP9 expression suggest a contribution of the channel to retinal ganglion cell death and response of distinct amacrine cells known to express AQP9 following traumatic injuries.

Bestrophin 2 is expressed in human non-pigmented ciliary epithelium but not retinal pigment epithelium.

PURPOSE: Mice in which bestrophin 2 (Best2) is disrupted exhibit changes in aqueous flow and drainage, resulting in a reduction in intraocular pressure in comparison to wild-type mice. Best2 encodes a putative anion channel localized uniquely to the basolateral plasma membrane of non-pigmented epithelium cells in mice. In this study, we examine the localization of Best2 in the human eye. METHODS: Rabbit polyclonal antibodies recognizing human Best2 (hBest2) were generated and characterized for use in western blot, immunoprecipitation, and immunofluorescence assays. The expression of hBest2 using these antibodies was examined using human donor eye tissues. RESULTS: We could not detect hBest2 in human ciliary bodies or other ocular tissues by western blot. However, when enriched by immunoprecipitation, hBest2 was identified in ciliary bodies, but not in the retinal pigment epithelium. Using immunofluorescence, we located hBest2 in the basolateral plasma membrane of non-pigmented epithelial cells. CONCLUSIONS: We found expression of hBest2 similar to mice only in NPE cells. These data suggest that Best2 may play a functional role in the regulation of aqueous flow and drainage in humans. We conclude that Best2 represents a new potential target for glaucoma therapy.

Financial incentives to influence maternal mortality in a low-income setting: making available 'money to transport' - experiences from Amarpatan, India.

OBJECTIVES: Only 40.7% women in India deliver in an institution; leaving many vulnerable to maternal morbidity and mortality (India has 22% of global maternal deaths). While limited accessibility to functioning institutions may account in part, a common reason why women deliver at home is poverty. A lack of readily available financial resources for families to draw upon at the time of labor to transport the mother to an institution, is often observed. This paper reports a yearlong collaborative intervention (between the University and Department of Health) to study if providing readily available and easily accessible funds for emergency transportation would reduce maternal deaths in a rural, low income, and high maternal mortality setting in central India. It aimed to obviate a deterrent to emergency obstetric care; the non-availability of resources with mothers when most needed. Issues in implementation are also discussed. METHODS: Maternal deaths were actively identified in block Amarpatan (0.2 million population) over a 2-year period. The project, with participation from local government and other groups, trained 482 local health care providers (public and private) to provide antenatal care. Emergency transport money (in cash) was placed with one provider in each village. Maternal mortality in the adjacent block (Maihar) was followed (as a 'control' block). RESULTS: Maternal deaths in Amarpatan decreased during the project year relative to the previous year, or in the control block the same year. DISCUSSION AND CONCLUSIONS: Issues in implementation of the cash incentive scheme are discussed. Although the intervention reduced maternal deaths in this low-income setting, chronic poverty and malnutrition are underlying structural problems that need to be addressed.

Pattern and trend of deliberate self-harm in western Nepal.

Acts of deliberate self-harm (DSH) not only affect the people directly involved, but also have grave psychological and social impact on the family and community. In the present study, a cohort of 173 cases of DSH reported from April 2002 to March 2005 was retrospectively analyzed, by perusing the medicolegal register maintained by the Emergency Department at the Western Regional Hospital, Pokhara in the Western Development Region of Nepal. The data were entered and analyzed using SPSS Version 10.1. More than two-thirds of total cases were females. About 60% of cases were observed in the age group of 15-24 years. Poisoning (89.6%) was the most preferred method of deliberate self-harm. Organophosphate pesticides were consumed in nearly two-thirds of the poisoning cases. The majority of cases were reported during the months of May to July and had occurred during the last quarter of the day. More than a twofold increase was observed in the frequency of cases during the 3-year study period. The said observations were compared and contrasted with the available literature across the globe. The presentation is concluded by highlighting the limitations encountered in Nepal and the scope to overcome the same.

Vasopressin-induced differential stimulation of AQP4 splice variants regulates the in-membrane assembly of orthogonal arrays.

Aquaporin-4 (AQP4) is a basolateral water channel in collecting duct principal cells and assembles into orthogonal array particles (OAPs), the size of which appears to depend on relative expression levels of AQP4 splice variants. Because the higher-order organization of AQP4 was perturbed by vasopressin in Brattleboro rats and phosphorylation sites have been identified on AQP4, we investigated whether vasopressin and forskolin (Fk) affect AQP4 assembly and/or expression in LLC-PK(1) cells stably transfected with the AQP4 splice variant M23, which is responsible for formation of OAPs, and/or the splice variant M1, which does not form OAPs. Our data show that [lys(8)]-vasopressin (LVP) and Fk treatment led to differential increases in expression levels of M23-AQP4 and M1-AQP4 that varied as a function of incubation time. At early time points (day 1) expression of M1 was significantly stimulated (4.5-fold), over that of M23 (1.6-fold), but after 3 days the expression of M23 became predominant (4.1-fold) over that of M1 (1.9-fold). This pattern of stimulation was dependent on an intact AQP4 residue serine 111 and required protein synthesis. In cells expressing both M1 and M23 (M1/M23 approximately 1), with small sized OAPs at the membrane, the LVP/Fk-induced stimulation of M23 was modified and mimicked that of M1 when expressed alone, suggesting a dominant role for M1. In Brattleboro kidney inner medulla, an 8-day chronic exposure to the vasopressin agonist (dDAVP) led to reduction in M1 and a significant increase in M23 immunoblot staining (M1/M23 = 2/3 --> 1/4). These results indicate that AQP4 organization and expression are regulated by vasopressin in vivo and in vitro and demonstrate that the dominant role for M1 is restricted to a one-to-one interaction between AQP4 splice variants that regulates the membrane expression of OAPs.

Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand.

Glaucomatous optic neuropathy causes blindness through the degeneration of retinal ganglion cells (RGCs) and their axons, which comprise the optic nerve. Glaucoma traditionally is associated with elevated intraocular pressure, but often occurs or may progress with intraocular pressure in the normal range. Like other diseases of the CNS, a subset of glaucoma has been proposed to involve an autoimmune component to help explain the loss of RGCs in the absence of elevated intraocular pressure. One hypothesis involves heat shock proteins (HSPs), because increased serum levels of HSP autoantibodies are prominent in some glaucoma patients with normal pressures. In the first direct support of this hypothesis, we found that HSP27 and HSP60 immunization in the Lewis rat induced RGC degeneration and axon loss 1-4 months later in vivo in a pattern with similarities to human glaucoma, including topographic specificity of cell loss. Infiltration of increased numbers of T-cells in the retina occurred much earlier, 14-21 d after HSP immunization, and appeared to be transient. In vitro studies found that T-cells activated by HSP immunization induced RGC apoptosis via the release of the inflammatory cytokine FasL, whereas HSP immunization induced activation of microglia cells and upregulation of the FasL receptor in RGCs. In summary, our results suggest that RGC degeneration in glaucoma for selected individuals likely involves failed immunoregulation of the T-cell-RGC axis and is thus a disturbance of both proapoptotic and protective pathways.