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The present pilot study investigating the minimum dose for short-course single and double-dose treatment of kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of immunological components for early detection of success and/or failure to cure. Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome. Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment. At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-gamma, IL-12 and TNF, and significant down-regulation of IL-10 and TGF-beta in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-gamma, IL-12 and TNF, and persistence of IL-10, despite decline in TGF-beta in culture supernatants, in apparently cured individuals, corresponded with relapse within 6-months of treatment. Immunological investigations revealed significant curative and non-curative immunomodulation 1-week posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was dose-independent, almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitive impact of the higher-dose on the immune response. TRIAL REGISTRATION NAME AND NUMBER: Clinical Trials Registry--India (CTRI) CTRI/2009/091/000764.

Human visceral leishmaniasis (VL), a potentially fatal disease, is most prevalent in the Indian subcontinent, East Africa and South America. Definite diagnosis and effective treatment are the primary needs for the control of VL. Diagnosis of VL has typically relied on microscopic examination of bone marrow/splenic aspirate, but serology and molecular methods are now better alternatives. The conventional drugs for treatment of VL have limitations including unresponsiveness, relapse, specific toxicities and parenteral administration lasting for long durations. Moreover, they are less effective in HIV-VL-coinfected patients. Registration of miltefosine and paromomycin, and preferential pricing of AmBisome has offered more choices for monotherapy and combination therapy for VL. Combination therapy will increase treatment efficacy and prevent the development of resistance. In addition, active case finding and vector control strategies will also have a positive impact in the control of VL. This article critically addresses the currently available diagnostic and treatment regimens for the control of VL.

Objective: humans' circadian rhythm is an important parameter in understanding current biological, physiological, and psychological status, which broadly affects physical fitness. The physiological mechanisms underlying circadian rhythms remain underexplored despite their potential impact on physical and mental health. The study aims to examine the effect of diurnal variations on cognitive and physical performance in female athletes. Methodology: a counterbalanced within-subjects repeated measures design was employed, involving 15 healthy female university students aged 18 to 25. Each participant underwent cognitive and physical performance tests at three distinct times—6 AM, 12 PM, and 6 PM—on separate days. Results: the study demonstrated a significant effect of diurnal variations on cognitive and physical performance indices. Discussion: cognitive performance showed varied patterns across time points. Perceptual reasoning, measured by the Müller-Lyer test, peaked in the morning and was lowest in the evening. Working memory, assessed via the span digit test, showed moderate values at noon and evening. Strength, measured by the vertical jump, was highest in the evening and lowest in the morning. As assessed by the Illinois Agility Test, agility peaked at noon, with the lowest values recorded in the morning. Conclusions: time of day significantly affects both cognitive and physical performance in female athletes. Strength peaks in the evening, agility at noon, and perceptual reasoning in the morning, while working memory shows moderate performance at noon and evening. These results suggest that athletes and coaches can optimize training and competition schedules based on diurnal cognitive and physical performance variations. Objetivo: El ritmo circadiano humano es un parámetro fundamental para comprender su estado biológico, fisiológico y psicológico actual, lo que influye ampliamente en la condición física. Los mecanismos fisiológicos subyacentes a los ritmos circadianos siguen estando poco explorados, a pesar de su posible impacto en la salud física y mental. Este estudio tiene como objetivo examinar el efecto de diferentes momentos del día en el rendimiento cognitivo y físico de atletas femeninas. Metodología: Se empleó un diseño de medidas repetidas contrabalanceado dentro de los sujetos, involucrando a 15 estudiantes universitarias sanas de entre 18 y 25 años. Cada participante realizó pruebas de rendimiento cognitivo y físico en tres momentos distintos del día—6 AM, 12 PM y 6 PM—en días separados. Resultados: El estudio mostró un efecto significativo de las variaciones diurnas en los índices de rendimiento cognitivo y físico. Discusión: El rendimiento cognitivo presentó patrones variables a lo largo del día. El razonamiento perceptivo, medido por la prueba de Müller-Lyer, alcanzó su punto máximo en la mañana y fue más bajo en la noche. La memoria de trabajo, evaluada mediante la prueba de amplitud de dígitos, mostró valores moderados al mediodía y en la noche. La fuerza, medida por el salto vertical, fue mayor en la noche y menor en la mañana. La agilidad, evaluada con la prueba de agilidad de Illinois, alcanzó su punto máximo al mediodía y registró los valores más bajos en la mañana. Conclusiones: La hora del día afecta significativamente el rendimiento cognitivo y físico en atletas femeninas. La fuerza alcanza su punto máximo en la noche, la agilidad al mediodía y el razonamiento perceptivo en la mañana, mientras que la memoria de trabajo muestra un rendimiento moderado al mediodía y en la noche. Estos resultados sugieren que los atletas y entrenadores pueden optimizar los horarios de entrenamiento y competición en función de las variaciones diurnas del rendimiento cognitivo y físico. Objectivo: O ritmo circadiano humano é um parâmetro fundamental para compreender o seu estado biológico, fisiológico e psicológico actual, o que influencia largamente a condição física. Os mecanismos fisiológicos subjacentes aos ritmos circadianos ainda estão a ser explorados, apesar do seu possível impacto na saúde física e mental. Este estudo tem como objetivo examinar o efeito de diferentes momentos do dia no desempenho cognitivo e físico de atletas do sexo feminino. Metodologia: Foi implementado um projeto de medidas repetitivas contrabalançadas dentro dos assuntos, envolvendo 15 estudantes universitários com idades compreendidas entre os 18 e os 25 anos. Cada participante realizou testes de desempenho cognitivo e físico em três momentos distintos do dia — 6h, 12h e 18h — em dias separados.Resultados: O estudo mostrou um efeito significativo das variações diurnas nos índices de desempenho cognitivo e físico.Discussão: O desempenho cognitivo apresenta variáveis ​​clientes ao longo do dia. O raciocínio perceptivo, medido pela tentativa de Müller-Lyer, atingiu o seu ponto máximo de manhã e foi mais baixo à noite. A memória de trabalho, avaliada através do teste de amplitude de dígitos, apresentou valores moderados ao meio-dia e à noite. A força, medida pelo salto vertical, foi maior na noite e menor na manhã. A agilidade, avaliada com o teste de agilidade de Illinois, atingiu o seu ponto máximo ao meio-dia e registou os valores mais baixos da manhã.Conclusões: A hora do dia afeta significativamente o encontro cognitivo e físico em atletas femininas. A força atinge o seu ponto máximo na noite, a agilidade na média e o raciocínio percetivo na manhã, enquanto a memória de trabalho apresenta um desempenho moderado ao meio-dia e à noite. Estes resultados sugerem que os atletas e treinadores podem otimizar os horários de treino e competição com base nas variações diurnas do desempenho cognitivo e físico.

Human infection with Leishmania results in diverse clinical and immunopathological situations. The capacity of the parasites to cause this wide range of disease manifestations depends upon their ability to evade the immune defense mechanisms by performing a well-tuned orchestra of hostparasite interactions inside the macrophages. While updated knowledge focus on the key role of cell-mediated immunity (CMI) in protection, the survival strategies of the parasites leads to the suppression of CMI which can further be aggravated by the co-infections with HIV, tuberculosis etc. The present review describes the immune mechanisms in human leishmaniasis with a special attention to visceral leishmaniasis or kala-azar, one of the most important epidemiological health problems in Indian subcontinent. Modulations of the both humoral and cell-mediated immune responses during asymptomatic infections, active disease and after successful chemotherapy are discussed. The components responsible for the regulation of the critical balance of Th1/Th2 type of responses are re-evaluated. Co-infection of HIV and visceral leishmaniasis and their interdependence has been addressed. Although the specific role of an elevated humoral response in kala-azar is yet to be established, attempts for its application in diagnosis, precisely for the development of field diagnostic techniques, are presented. Also discussed are attempts to utilize the immunogenic potentials of different leishmanial antigens in the development of anti-leishmanial vaccines.

Objectives To identify prevalence of pulmonary tuberculosis (TB) in severely malnourished children admitted to nutritional rehabilitation centers. Methods A multicenter cross-sectional study involving 41 nutrition rehabilitation centres (NRCs) across India was carried out to document prevalence of pulmonary tuberculosis in acute severe malnourished children admitted in NRCs. After training of the NRC staff to follow algorithm provided by national tuberculosis elimination program, children admitted to NRCs were screened for pulmonary tuberculosis. Results A total of 4356 children were enrolled across all the sites. Gastric aspirate for Cartridge based nucleic acid amplification test (CBNAAT), tuberculin skin test (TST) and X-ray film of chest were done in more than 99% of enrolled subjects. A total of 189 children (4.3%) had pulmonary tuberculosis. Eighty-seven (1.99%) were microbiologically confirmed by positive CBNAAT. On multivariate analysis, only significant association was with history of contact with TB patient in family. Conclusions The present results suggest that a significant proportion (>4%) of children admitted in NRCs suffer from pulmonary tuberculosis. It is feasible to improve diagnosis of tuberculosis as a whole and microbiologically confirmed TB.