A Cyclic Phosphoramidate Prodrug of 2'-Deoxy-2'-Fluoro-2'-C-Methylguanosine for the Treatment of Dengue Virus Infection.

Monophosphate prodrug analogs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine have been reported as potent inhibitors of hepatitis C virus (HCV) RNA-dependent RNA polymerase. These prodrugs also display potent anti-dengue virus activities in cellular assays although their prodrug moieties were designed to produce high levels of triphosphate in the liver. Since peripheral blood mononuclear cells (PBMCs) are among the major targets of dengue virus, different prodrug moieties were designed to effectively deliver 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate prodrugs and their corresponding triphosphates into PBMCs after oral administration. We identified a cyclic phosphoramidate, prodrug 17, demonstrating well-balanced anti-dengue virus cellular activity and in vitro stability profiles. We further determined the PBMC concentration of active triphosphate needed to inhibit virus replication by 50% (TP50). Compound 17 was assessed in an AG129 mouse model and demonstrated 1.6- and 2.2-log viremia reductions at 100 and 300 mg/kg twice a day (BID), respectively. At 100 mg/kg BID, the terminal triphosphate concentration in PBMCs exceeded the TP50 value, demonstrating TP50 as the target exposure for efficacy. In dogs, oral administration of compound 17 resulted in high PBMC triphosphate levels, exceeding the TP50 at 10 mg/kg. Unfortunately, 2-week dog toxicity studies at 30, 100, and 300 mg/kg/day showed that "no observed adverse effect level" (NOAEL) could not be achieved due to pulmonary inflammation and hemorrhage. The preclinical safety results suspended further development of compound 17. Nevertheless, present work has proven the concept that an efficacious monophosphate nucleoside prodrug could be developed for the potential treatment of dengue virus infection.

Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity.

BACKGROUND: Our recent study has shown that acute treatment with ethanol (EtOH) increases oxidative stress and cytotoxicity through cytochrome P450 2E1 (CYP2E1)-mediated pathway in U937 monocytic cells. U937 cells are derived from blood monocytes and are considered as the model system for HIV-related study. Since the prevalence of alcohol use in HIV-infected population is high, and HIV+ patients are on antiretroviral therapy (ART) soon after they are diagnosed, it is important to study the interactions between EtOH and ART in monocytes. METHODS: This study examined the chronic effects of EtOH and ART (darunavir/ritonavir), alone and in combination, on expression/levels of cytochrome P450 enzymes (CYPs), antioxidant enzymes (AOEs), reactive oxygen species (ROS), and cytotoxicity in U937 cells. The mRNA and protein levels were measured using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. ROS and cytotoxicity were measured using flow cytometry and cell viability assay, respectively. RESULTS: While chronic ART treatment increased CYP2E1 protein expression by 2-fold, EtOH and EtOH+ART increased CYP2E1 by ~5-fold. In contrast, ART and EtOH treatments decreased CYP3A4 protein expression by 38 ± 17% and 74 ± 15%, respectively, and the combination additively decreased CYP3A4 level by 90 ± 8%. Expressions of superoxide dismutase 1 (SOD1) and peroxiredoxin (PRDX6) were decreased by both EtOH and ART, however, the expressions of SOD2 and catalase were unaltered. These results suggested increased EtOH metabolism, increased ART accumulation, and decreased defense against ROS. Therefore, we determined the effects of EtOH and ART on ROS and cytotoxicity. While ART showed a slight increase, EtOH and EtOH+ART displayed significant increase in ROS and cytotoxicity. Moreover, the combination showed additive effects on ROS and cytotoxicity. CONCLUSIONS: These results suggest that chronic EtOH, in the absence and presence of ART, increases ROS and cytotoxicity in monocytes, perhaps via CYP- and AOE-mediated pathways. This study has clinical implications in HIV+ alcohol users who are on ART.

Correlates of Defaulting from MDT among Leprosy Patients.

In order to analyse the factors of demographic as well as disease related variables and their correlation with Rate of Defaulting (ROD) from Multi Drug Therapy (MDT) among leprosy patients, secondary data have been collected from 3,579 new cases registered for MDT, during a period of 4 years from 2007 to 2010 in four leprosy hospitals/ treatment centers across the four high endemic states viz. Uttar Pradesh, Chhattisgarh; Maharashtra and Andhra Pradesh. Year wise percentage of patients defaulted was calculated on aggregate as well as with reference to each centre and cross tabulated with demographic and disease related factors. Findings show that out of the total 3,579 new cases, 1944,(54.3%) defaulted with variation across centers ranged from 44 to 66 percent. Comparison of ROD against type of leprosy indicated that MB types defaulted (55.7%) more than PB (50.6%) types, (statistically significant difference, (p=0,04). ROD of male patients across the centers ranged from 45% to 67.7% in comparison with 42.4% to 61.5% of female patients. A-statistically significant difference (p=6.04) was found between the overall ROD of males (56.35%) and females (51.47%). The ROD among those with more severe disabilities (WHO Gr-2) ranged between 44% to 67.5% across the centers, while the same among those'with less severe disabilities (Gr-0&1) ranged from 42.6 to 72.7 percent. Comparison of ROD against severity of disability was found statistically significant only across 2 centers. No statistically significant variation was found when ROD of adult patients with refeince to each centr ranged between (43.6% to 65.4%) was compared with the same of children ranged beeIen (36.2% to 69.3%). Across each of these categories and centers,'the ROD remained consistent over the ,4 years. Based on the above findings'this may be concluded that male sex and MB types are significant correlates of default from treatment. Severity of disabilities plays significant role only in certain areas, probably due to other interfering factors, which needs to be further investiged.

Enhanced oxidative stress by alcohol use in HIV+ patients: possible involvement of cytochrome P450 2E1 and antioxidant enzymes.

BACKGROUND: Alcohol consumption is prevalent amongst HIV positive population. Importantly, chronic alcohol use is reported to exacerbate HIV pathogenesis. Although alcohol is known to increase oxidative stress, especially in the liver, there is no clinical evidence that alcohol increases oxidative stress in HIV positive patients. The mechanism by which alcohol increases oxidative stress in HIV positive patients is also unknown. METHODS: To examine the effects of alcohol use on oxidative stress we recruited HIV+ patients who reported mild-to-moderate alcohol use. Strict inclusion and exclusion criteria were applied to reduce the effect of other therapeutic drugs metabolized via the hepatic system as well as the effect of co-morbidities such as active tuberculosis on the interaction between alcohol and HIV infection, respectively. Blood samples were collected from HIV-negative alcohol-users and HIV positive alcohol-users followed by collection of plasma and isolation and fractionation of monocytes from peripheral blood. We then determined oxidative DNA damage, glutathione level, alcohol level, transcriptional level of cytochrome P450 2E1 (CYP2E1) and several antioxidant enzymes, and plasma level of cytokines. RESULTS: Compared to HIV-negative alcohol users, HIV-positive alcohol users demonstrated an increase in oxidative DNA damage in both plasma and CD14+ monocytes, as well as, a relative increase in oxidized/reduced glutathione (GSSG/GSH) in plasma samples. These results suggest an increase in oxidative stress in HIV-positive alcohol users compared with HIV-negative alcohol users. We also examined whether alcohol metabolism, perhaps by CYP2E1, and antioxidant enzymes are involved in alcohol-mediated increased oxidative stress in HIV-positive patients. The results showed a lower plasma alcohol level, which was associated with an increased level of CYP2E1 mRNA in monocytes, in HIV-positive alcohol users compared with HIV-negative alcohol users. Furthermore, the transcription of major antioxidants enzymes (catalase, SOD1, SOD2, GSTK1), and their transcription factor, Nrf2, were reduced in monocytes obtained from HIV positive alcohol users compared to the HIV-negative alcohol user group. However, no significant change in levels of five major cytokines/chemokines were observed between the two groups. CONCLUSIONS: The data suggests that alcohol increases oxidative stress in HIV+ patients, perhaps through CYP2E1- and antioxidant enzymes-mediated pathways. The enhanced oxidative stress is accompanied by a failure of cellular antioxidant mechanisms to maintain redox homeostasis. Overall, the enhanced oxidative stress in monocytes may exacerbate HIV pathogenesis in HIV positive alcohol users.

Evaluation of 1,2,5-thiadiazoles as modulators of M1/M5 muscarinic receptor subtypes.

Studies have demonstrated the presence of allosteric binding sites on each of the muscarinic acetylcholine receptor (mAChR) subtypes. Since most drugs targeting muscarinic receptors bind to the highly conserved orthosteric binding site, they fail to achieve appreciable subtype selectivity. Targeting non-conserved allosteric sites may provide a new way of enhancing selectivity for individual subtypes of muscarinic receptor. Tetra(ethyleneglycol)(3-methoxy-1,2,5-thiadiazol-4-yl)[3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether, CDD-0304 (10), was found to be a M1/2/4 selective muscarinic agonist and might prove useful in treating the symptoms associated with schizophrenia (J. Med. Chem.2003, 46, 4273). It was hypothesized that the observed subtype selectivity demonstrated by 10 may be due to its ability to function as a bitopic ligand (J. Med. Chem.2006, 49, 7518). To further investigate this possibility, a novel series of compounds was synthesized using a 1,2,5-thiadiazole moiety along with varying lengths of a polyethylene glycol linker and terminal groups, for evaluation as potential allosteric modulators of muscarinic receptors. Preliminary biological studies were performed using carbachol to stimulate M1 and M5 receptors. No significant agonist activity was observed at either M1 or M5 receptors for any of the compounds. Compound 18, 2-(4-methoxy-1,2,5-thiadiazol-3-yloxy)-N,N-dimethylethanamine fumarate (CDD-0361F) was found to block the effects of carbachol at M5 muscarinic receptors.

Effects of ceftriaxone on systemic and central expression of anti- and pro-inflammatory cytokines in alcohol-preferring (P) rats exposed to ethanol.

AIMS: Determine the effect of reduction in ethanol consumption by alcohol-preferring (P) rats, following ceftriaxone treatment, on the cytokines levels in prefrontal cortex (PFC) and plasma. METHODS: Following 5 weeks of free access to ethanol (15 and 30%), P rats were treated daily with ceftriaxone or saline vehicle for either 2 or 5 consecutive days. Plasma and PFC were collected from ceftriaxone- and saline vehicle-treated groups, and assayed for the levels of pro- and anti-inflammatory cytokines. RESULTS: A significant increase in the plasma level of anti-inflammatory cytokine IL-10 was observed in the ceftriaxone-treated group when compared with the saline-treated group in both the 2-day and 5-day treatments. Furthermore, ceftriaxone treatment for 2 days induced reduction in TNFα level in both plasma and PFC. Additionally, ceftriaxone treatment for 2 days significantly reduced the IFNγ level in PFC. CONCLUSION: These findings show the ability of ceftriaxone to reduce alcohol consumption and induce modulation of the anti-inflammatory and pro-inflammatory cytokines levels in P rats.

Leprosy and tuberculosis concomitant infection: a poorly understood, age-old relationship.

Historically, archaeological evidence, post-mortem findings and retrospective analysis of leprosy institutions' data demonstrates a high observed incidence of concomitant infection with leprosy and tuberculosis (TB). However, reports of concomitant infection in the modern literature remain scarce, with estimates of annual new case detection rates of concomitant infection at approximately 0.02 cases per 100,000 population. Whilst the mechanism for this apparent decline in concomitant infections remains unclear, further research on this topic has remained relatively neglected. Modelling of the interaction of the two organisms has suggested that the apparent decline in observations of concomitant infection may be due to the protective effects of cross immunity, whilst more recently others have questioned whether it is a more harmful relationship, predisposing towards increased host mortality. We review recent evidence, comparing it to previously held understanding on the epidemiological relationship and our own experience of concomitant infection. From this discussion, we highlight several under-investigated areas, which may lead to improvements in the future delivery of leprosy management and services, as well as enhance understanding in other fields of infection management. These include, a) highlighting the need for greater understanding of host immunogenetics involved in concomitant infection, b) whether prolonged courses of high dose steroids pre-dispose to TB infection? and, c) whether there is a risk of rifampicin resistance developing in leprosy patients treated in the face of undiagnosed TB and other infections? Longitudinal work is still required to characterise these temporal relationships further and add to the current paucity of literature on this subject matter.

Determinants of rural women's participation in India's National Leprosy Eradication Programme.

A multistage representative random sample of women and men from each of the 3 states of Bihar, Uttar Pradesh and West Bengal, from the rural blocks where the Leprosy Mission Hospitals were located were selected during 2010 to identify relevant factors that are preventing active participation of women and suggest corrective steps. Adult men and women were interviewed in depth, using a detailed checklist by the first author. A total of 1239 respondents 634 women and 605 men, were interviewed, only 44 women (7%) claimed that they had earlier participated in leprosy work, about 92% of the women felt that they had the potential to take part in leprosy work, and 70% showed willingness to participate. Factors that would encourage and facilitate more women to participate in leprosy work, included financial support (32.8%), convincing the family to grant permission (88%), and delegating them to work in proximity to their residences (15%). Some women respondents (11.0%) felt that they would provide their services voluntarily for social good. Women suggested that work should be delegated as per their capabilities and skills, and they should be given proper orientation, training and guidance. Hardly 5% of ASHA's in the clusters examined participated in leprosy related work, which needs stringent steps to re-orient and encourage them to undertake leprosy related work. It is concluded that rural Indian women are keen to play an important role in the national leprosy eradication program, with minimal support from the government and nongovernmental agencies in a truly community-based approach. This will benefit vast numbers of leprosy affected women as well as others.

Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

Facial sensory loss in multi-bacillary leprosy patients.

Sensation over the face was estimated using the Semmes-Weinstein's monofilament (target force 0-05 gms) in a cohort of multi-bacillary (MB) patients whose clinical and ocular characteristics were available at the time of leprosy diagnosis. Among the 190 MB patients examined, 56 (30%) had areas of sensory impairment somewhere on the face and 43 (23%) had sensory deficit over the lids and/or the malar area. Lagophthalmos (adjusted OR 8.96, 95% CI 0.96-83.50), Type 1 reaction (aOR 2.47, 95% CI 1.11-5-52), history of reactions (aOR 6.36, 95% CI 2.40-16.85) and glove and stocking anaesthesia (aOR 3.49, 95% CI 1-40-8.70) were associated with impaired facial sensation. Hypoesthesia restricted to areas over the lids and/or malar area showed a stronger association with lagophthalmos (aOR 17.5, 95% CI 1.98-154.36). Loss of facial sensation appears to be associated with lagophthalmos in MB patients.

Peroneal strength as an indicator in selecting route of tibialis posterior transfer for foot drop correction in leprosy.

OBJECTIVES: Tibialis posterior tendon transfer (TPT) technique, using either the Circum-tibial (CT) or Inter-osseus (IO) route is the standard surgical technique to correct foot drop. The selection of the route of transfer is usually dependent on the surgeon's preference. This study aims to identify criteria to help make that selection. SUBJECTS AND METHODS: A study was carried out on 381 feet during the period 1999 to 2010. All the patients operated during this period were included in the study. The CT route was used for those with peronei power 4 or 5, while the IO route was used when peronei power was 3 or less. RESULTS: In this case series the mean effective range of motion (above 90 degrees) was 11 and 12 degrees in CT and IO routes, respectively. The results were comparable in terms of rest position, active dorsiflexion and effective range of motion. All patients had a post-operative heel to toe gait, except for one of the 381 operated feet. Only three of the 381 feet had a reduction in navicular height of more than 2 cm, the medial arch being maintained in the others. CONCLUSIONS: TPT is a standard procedure to correct foot drop deformity in leprosy. Pre-selection for route of transfer, CT or IO, based on peronei strength avoids the complication of iatrogenic inversion. The technique of insertion and routine tendo-achilles lengthening provides a good range of movement. The deep tunnelling has not compromised the results, while giving excellent cosmetic appearance.

A conceptual protocol for translational research in the complex reality of leprosy.

In response to an international strategy to prioritise and focus research efforts in leprosy, this conceptual protocol outlines a research plan to address key translational research priorities. The protocol describes in broad terms a five-phase psychosocial and service-related research programme to facilitate: prevention of delay in diagnosis, improvement of adherence with multi-drug therapy, the roll out of chemoprophylaxis and increased participation in community based rehabilitation. The protocol proposes a model of research utilisation and the notion of complexity to form an integrating theoretical framework for exploring and enhancing research translation. The proposed sequential research programme is characterised by traditional and participatory strategies, culminating in participatory implementation of findings. Publication of the conceptual protocol prior to operationalisation and commencement of the research aims to encourage debate, refinement of strategies, collaboration and the optimisation of resources.

Disability adjusted working life years (DAWLYs) of leprosy affected persons in India.

BACKGROUND & OBJECTIVES: Disability-adjusted life years (DALYs) have been accepted as a useful method to estimate the burden of disease, and can be adapted to determine the number of productive years lost due to the disability. DALY has been reported for many studies but not for leprosy. Hence this study was carried out in three States of India. In view of the fact that in this study, productive working years are used, the term is modified as DAWLY. METHODS: A representative random sample of 150 leprosy affected persons, 50 from each States of Uttar Pradesh, West Bengal and Chhattisgarh, was chosen, and data were collected on detailed work-life history, occupation, time when leprosy was discovered, reported and treatment started, break of job/loss of income due to leprosy. The loss of wages and durations were used to compute the life-years lost due to leprosy, and summarized over the average total duration of 42 years of productive work-life from 18 to 60 years. The percentage losses were determined and differences tested for statistical significance. RESULTS: The overall mean (± SE) disability adjusted working life years was 28.6 (±0.67), a reduction of 13.4 yr from the ideal productive working life period of 42 yr. The youngest patients with disability had a reduction of 41.4 per cent, as compared to the oldest patients. There was a significant increase in loss based on year for those whose disability started earlier (P=0.0024). INTERPRETATION & CONCLUSIONS: On an average, 30 per cent of the leprosy affected person's work life is lost due to disability.

Integrating risk and resilience approaches to catastrophe management in engineering systems.

Recent natural and man-made catastrophes, such as the Fukushima nuclear power plant, flooding caused by Hurricane Katrina, the Deepwater Horizon oil spill, the Haiti earthquake, and the mortgage derivatives crisis, have renewed interest in the concept of resilience, especially as it relates to complex systems vulnerable to multiple or cascading failures. Although the meaning of resilience is contested in different contexts, in general resilience is understood to mean the capacity to adapt to changing conditions without catastrophic loss of form or function. In the context of engineering systems, this has sometimes been interpreted as the probability that system conditions might exceed an irrevocable tipping point. However, we argue that this approach improperly conflates resilience and risk perspectives by expressing resilience exclusively in risk terms. In contrast, we describe resilience as an emergent property of what an engineering system does, rather than a static property the system has. Therefore, resilience cannot be measured at the systems scale solely from examination of component parts. Instead, resilience is better understood as the outcome of a recursive process that includes: sensing, anticipation, learning, and adaptation. In this approach, resilience analysis can be understood as differentiable from, but complementary to, risk analysis, with important implications for the adaptive management of complex, coupled engineering systems. Management of the 2011 flooding in the Mississippi River Basin is discussed as an example of the successes and challenges of resilience-based management of complex natural systems that have been extensively altered by engineered structures.

Time trends in MB-PB ratio among untreated leprosy patients attending a referral hospital in UP, India during 2001 to 2010.

Secular trends in incidence of leprosy serve as a powerful tool in determining progress in reaching eradication. However, the interpretation of these trends must take into account both operational and epidemiological factors. A study was done to assess a time trend in the ratios of MB & PB from 2001 to 2010 based on the leprosy patients registered in a referral hospital in UP, India. Data were analyzed based on the gender, age and residence. Regardless of these factors, MB proportion shows no significant trends. These findings are discussed and it is concluded that we are no more close to eradication as compared to the status over a decade ago. Hence, much greater efforts will be required to promote early detections of MB cases, whether children or adults, male or female.

Nursing interventions to manage anxiety levels of female inpatients admitted first time in a leprosy hospital.

Leprosy causes not just physical disabilities but mental and psycho social problems which are further more enhanced in women due to their submissive and secondary role in an Indian culture. This is reflected in their reluctance and delay in seeking hospitalization and generates great anxiety while admitted as inpatients. Appropriate nursing care can relieve much anxiety and help in faster healing. This paper presents the findings from such research carried out at a leprosy referral hospitalin north India. Adult female leprosy patients newly admitted for the first time in a leprosy referral hospital were interviewed in depth using Hamilton Anxiety Rating Scale and observed before and after implementing a customized nursing care plan. On admission, out of 40 women admitted more than 80% showed moderate or severe anxiety. After well planned nursing interventions only 2 continued to have severe anxiety, and a majority in all age groups showed significant reductions in anxiety levels, and responded well to leprosy care at the hospital. Well planned nursing care reduces or minimizes anxiety levels of female leprosy patients admitted first time in the hospital, and should become a standard practice in all hospital admissions.

Impact of COVID-19 pandemic on cross-country runners: changes in training, sleep, diet, and mental health.

Objective: Determine the impact of the COVID-19 pandemic on the changes in training, sleep, diet, and mental health of cross-country runners. Participants: Cross-country runners from NCAA Division II institutes. Methods: Wilcoxon signed-rank test was performed to analyze survey responses to ordinal questions on the survey while Spearman's rank correlation analysis (ρ) was used to calculate correlation between after the start of pandemic questions. Data was marked significant at p < 0.05. Results: Analysis of the survey responses revealed that cross-country runners were more likely to experience feelings of depression (p < 0.001), lack of motivation (p < 0.001), and higher daily stress (p < 0.001) after the start of the pandemic. After the start of the pandemic, runners running less days per week were more likely to report an increased feeling of depression (ρ=-0.315, p = 0.008) and lack of motivation (ρ=-0.458, p < 0.001). Conclusions: The present study underscores the importance of training, sleep, diet, and mental health amongst cross-country runners.

Utilization of kidneys with similar kidney donor risk index values from standard versus expanded criteria donors.

With the shortage of standard criteria donor (SCD) kidneys, efficient expanded criteria donor (ECD) kidney utilization has become more vital. We investigated the effects of the ECD label on kidney recovery, utilization and outcomes. Using data from the Scientific Registry of Transplant Recipients from November 2002 to May 2010, we determined recovery and transplant rates, and modeled discard risk, for kidneys within a range of kidney donor risk index (KDRI) 1.4-2.1 that included both SCD and ECD kidneys. To further compare similar quality kidneys, these kidneys were again divided into three KDRI intervals. Overall, ECD kidneys had higher recovery rates, but lower transplant rates. However, within each KDRI interval, SCD and ECD kidneys were transplanted at similar rates. Overall, there was increased risk for discard for biopsied kidneys. SCD kidneys in the lower two KDRI intervals had the highest risk of discard if biopsied. Pumped kidneys had a lower risk of discard, which was modulated by KDRI for SCD kidneys but not ECD kidneys. Although overall ECD graft survival was worse than SCD, there were no differences within individual KDRI intervals. Thus, ECD designation adversely affects neither utilization nor outcomes beyond that predicted by KDRI.

Help-seeking habits of untreated leprosy patients reporting to a referral hospital in Uttar Pradesh, India.

In a potentially disabling disease like leprosy, the need for prompt diagnosis and start of treatment cannot be over-emphasized. With the advent of massive Information, Education and Communication (IEC) strategies and easy accessibility of free multi drug therapy (MDT), delay in treatment is more dependent on patient initiative and subsequent health seeking habits. To study the factors contributing to delay, a random sample of 86 new untreated leprosy patients presenting to The Leprosy Mission Community Hospital, Naini, Allahabad during 2011 were interviewed in depth with the help of a check list. 61% of patients had disability at first presentation. The most common first symptom was a hypopigmented patch. Mean delay was found to be 25.9 months. Reasons for delay varied from ignorance aboutthe symptoms and signs of the disease, monitoring of symptoms in the hope that they would disappear by themselves and lack of vigilance among local medical practitioners in the lower levels of the health system. The authors discuss the typical sequence of events that contributed to delay at each stage before finally presenting at a referral hospital. It is necessary to outline recommendations to address delay in terms of intense health education campaigns, mass communication strategies and developing a high index of suspicion among primary health care givers.

Nutritional status of leprosy patients in India.

Across-sectional epidemiological study was carried out at a Leprosy Referral Hospital in Delhi to assess the nutritional status of multibacillary leprosy patients in comparison to the general population using BMI. 150 people affected with multibacillary leprosy were included in the study, of whom 108 (72%) had WHO Grade 2 disability. 100 non leprosy patients were also included as a control group. Socio-demographic and clinical details as well as their height and weight were measured and the BMI computed. The findings clearly showed that under-nutrition (BMI < 18.5) was more common in people affected by leprosy than in those without leprosy, regardless of age or sex. Presence of disability made the incidence of under-nutrition more likely. The duration of disease, number of lesions or bacterial index had no impact on the level of nutrition. There may be multiple factors working together to lead to this under-nutrition and these are discussed briefly. If, we aim to provide high quality services with a holistic approach, a mandatory BMI should be calculated for every patient and if under nourished, a qualitative diet summary should be done and suitable nutritional advice given. Further, studies are needed for a better understanding of the occurrence and progression of under-nutrition in leprosy to find efficient ways to combat this problem.