Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
Trop Doct ; : 49475520953647, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32903147

RESUMO

Cases of kala-azar reported during 2013-2018 in Bihar, India were retrospectively analysed. Of 2187 villages reporting cases of kala-azar in 2018, 573 (26.2%) had reported no case in the previous five years but contributed to 20% of disease burden in 2018. On applying potential thresholds of kala-azar outbreaks, 805, 519 and 103 villages reported more than twice, thrice and five times their previous five-year annual average in 2018, respectively. Indoor residual spraying (IRS) in villages reporting any case of kala-azar in the past three years as per current guidelines could cover 72% of incident cases in 2018 vis-a-vis 80% if villages reporting cases in the past five years were considered. Therefore, IRS may be expanded to villages reporting cases in the past five years. Village case trends can be utilised to configure potential outbreak alarms (early warning and response system) on a pre-organised dashboard. A data-driven strategy for villages newly reporting cases and those in potential outbreak situations could prove effective in achieving and sustaining the elimination of kala-azar.

3.
Trans R Soc Trop Med Hyg ; 114(7): 549-552, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32478835

RESUMO

BACKGROUND: The visceral leishmaniasis (kala-azar) elimination programme in India relies on indoor residual spraying (IRS) for sand-fly vector control. Insecticide supplied by a new manufacturer was introduced for IRS in 2019. We aimed to explore whether this led to a change in insecticide quantity being used in the field. METHODS: We compared measurements of weights of 250 mL of insecticide powder of two different manufacturers using a certified and calibrated weighing instrument. RESULTS: The density of insecticide supplied in 2019 was 43.4% lower than that in 2018, thereby leading to underdosing during current IRS activity. CONCLUSIONS: Insecticide-measuring containers should be recalibrated prior to every IRS round and also when an insecticide manufacturer changes, so that the insecticide dose is maintained within the recommended range.

4.
Sci Rep ; 10(1): 7992, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409687

RESUMO

The last decade has witnessed a swiftly increasing interest in the design and production of novel multivalent molecules as powerful alternatives for conventional antibodies in the fight against cancer and infectious diseases. However, while it is widely accepted that large-scale flexibility (10-100 nm) and free/constrained dynamics (100 ns -µs) control the activity of such novel molecules, computational strategies at the mesoscale still lag behind experiments in optimizing the design of crucial features, such as the binding cooperativity (a.k.a. avidity). In this study, we introduced different coarse-grained models of a polymer-linked, two-nanobody composite molecule, with the aim of laying down the physical bases of a thorough computational drug design protocol at the mesoscale. We show that the calculation of suitable potentials of mean force allows one to apprehend the nature, range and strength of the thermodynamic forces that govern the motion of free and wall-tethered molecules. Furthermore, we develop a simple computational strategy to quantify the encounter/dissociation dynamics between the free end of a wall-tethered molecule and the surface, at the roots of binding cooperativity. This procedure allows one to pinpoint the role of internal flexibility and weak non-specific interactions on the kinetic constants of the nanobody-wall encounter and dissociation. Finally, we quantify the role and weight of rare events, which are expected to play a major role in real-life situations, such as in the immune synapse, where the binding kinetics is likely dominated by fluctuations.

5.
BMC Infect Dis ; 20(1): 10, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906924

RESUMO

BACKGROUND: A visceral leishmaniasis outbreak was reported from a village in a low-endemic district of Bihar, India. METHODS: Outbreak investigation with house-to-house search and rapid test of kala-azar suspects and contacts was carried out. Sandfly collection and cone bio-assay was done as part of entomological study. RESULTS: A spatially and temporally clustered kala-azar outbreak was found at Kosra village in Sheikhpura district with 70 cases reported till December 2018. Delay of more than a year was found between diagnosis and treatment of the index case. The southern hamlet with socio-economically disadvantaged migrant population was several times more affected than rest of the village (attack rate of 19.0% vs 0.5% respectively, ORMH = 39.2, 95% CI 18.2-84.4). The median durations between onset of fever to first contact with any health services, onset to kala-azar diagnosis, diagnosis to treatment were 10 days (IQR 4-18), 30 days (IQR 17-73) and 1 day (IQR 0.5 to 3), respectively, for 50 kala-azar cases assessed till June 2017. Three-fourths of these kala-azar cases had out-of-pocket medical expenditure for their condition. Known risk factors for kala-azar such as illiteracy, poverty, belonging to socially disadvantaged community, migration, residing in kutcha houses, sleeping in rooms with unplastered walls and non-use of mosquito nets were present in majority of these cases. Only half the dwellings of the kala-azar cases were fully sprayed. Fully gravid female P. argentipes collected post indoor residual spraying (IRS) and low sandfly mortality on cone-bioassay indicated poor effectiveness of vector control. CONCLUSIONS: There is need to focus on low-endemic areas of kala-azar. The elimination programme should implement a routine framework for kala-azar outbreak response. Complete case-finding, use of quality-compliant insecticide and coverage of all sprayable surfaces in IRS could help interrupt transmission during outbreaks.


Assuntos
Surtos de Doenças , Leishmaniose Visceral/epidemiologia , Migrantes , Animais , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Incidência , Índia/epidemiologia , Controle de Insetos/estatística & dados numéricos , Inseticidas/administração & dosagem , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/terapia , Leishmaniose Visceral/transmissão , Psychodidae/fisiologia , Fatores de Risco
6.
J Phys Chem B ; 124(5): 727-734, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-31917571

RESUMO

The cell is an extremely complex environment, notably highly crowded, segmented, and confining. Overall, there is overwhelming and ever-growing evidence that to understand how biochemical reactions proceed in vivo, one cannot separate the biochemical actors from their environment. Effects such as excluded volume, obstructed diffusion, weak nonspecific interactions, and fluctuations all team up to steer biochemical reactions often very far from what is observed in ideal conditions. In this paper, we use Ficoll PM70 and PEG 6000 to build an artificial crowded milieu of controlled composition and density in order to assess how such environments influence the biocatalytic activity of lactate dehydrogenase (LDH). Our measurements show that the normalized apparent affinity and maximum velocity decrease in the same fashion, a behavior reminiscent of uncompetitive inhibition, with PEG resulting in the largest reduction. In line with previous studies on other enzymes of the same family, and in agreement with the known role of a surface loop involved in enzyme isomerization and regulation of access to the active site, we suggest that the crowding matrix interferes with the conformational ensemble of the enzyme. This likely results in both impaired enzyme-complex isomerization and thwarted product release. Molecular dynamics simulations confirm that excluded-volume effects lead to an entropic force that effectively tends to push the loop closed, thereby effectively shifting the conformational ensemble of the enzyme in favor of a more stable complex isoform. Overall, our study substantiates the idea that most biochemical kinetics cannot be fully explained without including the subtle action of the environment where they take place naturally, in particular accounting for important factors such as excluded-volume effects and also weak nonspecific interactions when present, confinement, and fluctuations.

7.
Trop Doct ; 50(1): 37-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31610724

RESUMO

A 12-week course of miltefosine (MF) is recommended in India for the treatment of post-kala-azar dermal leishmaniasis (PKDL). We report a case series of four patients with PKDL, across three districts of Bihar state, who developed eye complications during treatment. They presented with acute scleritis and corneal infiltration with or without corneal ulceration. One patient solely with corneal infiltration recovered completely. The three others with corneal ulceration healed with corneal opacificity. One patient with bilateral eye involvement underwent corneal transplantation to prevent blindness. All adverse events were graded as certain using the World Health Organization-Uppsala Monitoring Centre causality assessment scale. There is need to counsel patients regarding possible adverse ocular events during MF treatment, to expand pharmacovigilance to all primary health centres in kala-azar endemic areas, and to update drug safety information considering the emerging evidence.


Assuntos
Antiprotozoários/efeitos adversos , Oftalmopatias/induzido quimicamente , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Adulto , Antiprotozoários/uso terapêutico , Criança , Oftalmopatias/patologia , Oftalmopatias/fisiopatologia , Oftalmopatias/terapia , Feminino , Humanos , Índia/epidemiologia , Leishmaniose Visceral/epidemiologia , Masculino , Pessoa de Meia-Idade , Fosforilcolina/efeitos adversos , Fosforilcolina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
8.
Soft Matter ; 16(3): 634-641, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31840704

RESUMO

Several analytical calculations and computer simulations propose that cylindrical monodispersive rods having an aspect ratio (ratio of length to diameter) greater than 4 can exhibit liquid crystal (LC) ordering. But, recent experiments demonstrated the signature of LC ordering in systems of 4- to 20-base pair (bp) long nucleic acids (NAs) that do not satisfy the shape anisotropy criterion. Mechanisms of end-to-end adhesion and stacking have been proposed to explain this phenomenon. In this study, using all-atom molecular dynamics (MD) simulation, we explicitly verify the end-to-end stacking of double-stranded RNA (dsRNA) and demonstrate the LC ordering at the microscopic level. Using umbrella sampling (US) calculation, we quantify the potential of mean force (PMF) between two dsRNAs for various reaction coordinates (RCs) and compare our results with previously reported PMFs for double-stranded DNA (dsDNA). The PMF profiles demonstrate the anisotropic nature of inter-NA interaction. We find that, like dsDNA, dsRNA also prefers to stack on top of each other while repelling sideways, leading to the formation of supra-molecular-columns that undergo LC ordering at high NA volume fraction (φ). We also demonstrate and quantify the nematic ordering of the RNAs using several hundred nanosecond-long MD simulations that remain almost invariant for different initial configurations and under different external physiological conditions.


Assuntos
Cristais Líquidos/química , Simulação de Dinâmica Molecular , Ácidos Nucleicos/química , Anisotropia , Conformação de Ácido Nucleico , Termodinâmica
9.
J Phys Chem B ; 124(2): 314-323, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31867971

RESUMO

We report equilibrium and nonequilibrium molecular dynamics (MD) simulations of two nucleosome core particles (NCPs) stacked with their dyad axes oriented in parallel or antiparallel fashion. From the equilibrium trajectories, we determine the bridging behavior of different histone tails and observe that different sets of histone tails play important roles in the two orientations in stabilizing the NCP stack. While the H4 and H2A tails play important intermediary roles in the parallel stack, the H3 and H2B tails are important in the antiparallel stack. We use steered MD simulations to unstack the two NCPs and find a stark difference in their unstacking pathways. While the average rupture force was found to be higher for the parallel stack, the work done for complete unstacking was similar for both orientations. We use Jarzynski equality to determine the PMF profiles along the unstacking pathway, relate our findings to the behavior of NCP mesophases, and derive insights into the enigmatic nucleosomal organization in the chromatin fiber.

10.
J Clin Orthop Trauma ; 10(5): 969-971, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528077

RESUMO

Instrumentation breakage around hip joint can pose a challenging situation considering its vicinity to several vital structures. Broken fragments carry the risk of migration and thus should be removed as early as possible. A case of successful retrieval of broken tip of cephalomedullary lag screw reamer of a cephalomedullary nail, in basicervical region of femoral neck, during fixation of a subtrochanteric femoral fracture has been reported. Literature review has been done to suggest techniques to tackle similar situations using simple and commonly available instruments.

11.
Lancet ; 393(10174): 871, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30837138
13.
J Pediatr Neurosci ; 12(1): 46-48, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28553380

RESUMO

Encephalocele is a rare lesion, being an embryological mesodermal anomaly which results in a defect in the cranium and dura, associated with herniation of meninges, cerebrospinal fluid, or brain tissues through a defect usually covered by scalp. Surgical management of children with giant occipital encephalocele requires careful attention to pediatric anesthetic and surgical principles. We present a case of a giant occipital encephalocele highlighting the problems encountered in its management.

14.
Phys Rev E ; 95(3-1): 032702, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28415169

RESUMO

Recent experiments have shown that short double-stranded DNA (dsDNA) fragments having six- to 20-base pairs exhibit various liquid crystalline phases. This violates the condition of minimum molecular shape anisotropy that analytical theories demand for liquid crystalline ordering. It has been hypothesized that the liquid crystalline ordering is the result of end-to-end stacking of dsDNA to form long supramolecular columns which satisfy the shape anisotropy criterion necessary for ordering. To probe the thermodynamic feasibility of this process, we perform molecular dynamics simulations on ultrashort (four base pair long) dsDNA fragments, quantify the strong end-to-end attraction between them, and demonstrate that the nematic ordering of the self-assembled stacked columns is retained for a large range of temperature and salt concentration.


Assuntos
DNA/química , DNA/metabolismo , Cristais Líquidos/química , Simulação de Dinâmica Molecular , Modelos Genéticos , Sais/química , Termodinâmica
15.
J Phys Chem B ; 120(12): 3048-60, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-26931280

RESUMO

We report the first atomistic simulation of two stacked nucleosome core particles (NCPs), with an aim to understand, in molecular detail, how they interact, the effect of salt concentration, and how different histone tails contribute to their interaction, with a special emphasis on the H4 tail, known to have the largest stabilizing effect on the NCP-NCP interaction. We do not observe specific K16-mediated interaction between the H4 tail and the H2A-H2B acidic patch, in contrast with the findings from crystallographic studies, but find that the stacking was stable even in the absence of this interaction. We perform simulations with the H4 tail (partially/completely) removed and find that the region between LYS-16 and LYS-20 of the H4 tail holds special importance in mediating the inter-NCP interaction. Performing similar tail-clipped simulations with the H3 tail removed, we compare the roles of the H3 and H4 tails in maintaining the stacking. We discuss the relevance of our simulation results to the bilayer and other liquid-crystalline phases exhibited by NCPs in vitro and, through an analysis of the histone-histone interface, identify the interactions that could possibly stabilize the inter-NCP interaction in these columnar mesophases. Through the mechanical disruption of the stacked nucleosome system using steered molecular dynamics, we quantify the strength of inter-NCP stacking in the presence and absence of salt. We disrupt the stacking at some specific sites of internucleosomal tail-DNA contact and perform a comparative quantification of the binding strengths of various tails in stabilizing the stacking. We also examine how hydrophobic interactions may contribute to the overall stability of the stacking and find a marked difference in the role of hydrophobic forces as compared with electrostatic forces in determining the stability of the stacked nucleosome system.


Assuntos
Simulação de Dinâmica Molecular , Nucleossomos/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula
16.
Nanoscale ; 7(44): 18628-41, 2015 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-26495445

RESUMO

The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude the CD4 binding site on gp120, suggesting that SPL7013 does not prevent the binding of R5 gp120 to CD4. Using MD simulations to compute binding energies of several docked structures, we find that SPL7013 binding to gp120 significantly weakens the gp120-CD4 complex. Finally, we use steered molecular dynamics (SMD) to study the kinetics of the dissociation of the gp120-CD4 complex in the absence of the dendrimer and with the dendrimer bound in each of the several stable configurations to gp120. We find that SPL7013 significantly lowers the force required to rupture the gp120-CD4 complex and accelerates its dissociation. Taken together, our findings suggest that SPL7013 compromises the stability of the R5 gp120-CD4 complex, potentially preventing the accrual of the requisite number of gp120-CD4 complexes across the virus-cell interface, thereby blocking virus entry.


Assuntos
Antígenos CD4/química , Dendrímeros/química , Proteína gp120 do Envelope de HIV/química , HIV-1/química , Complexos Multiproteicos/química , Polilisina/química , Substituição de Aminoácidos , Sítios de Ligação , Antígenos CD4/genética , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , Humanos , Complexos Multiproteicos/genética , Mutação de Sentido Incorreto , Estabilidade Proteica
17.
J Phys Chem B ; 119(34): 11146-56, 2015 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-26134918

RESUMO

Active biological processes like transcription, replication, recombination, DNA repair, and DNA packaging encounter bent DNA. Machineries associated with these processes interact with the DNA at short length (<100 base pair) scale. Thus, the study of elasticity of DNA at such length scale is very important. We use fully atomistic molecular dynamics (MD) simulations along with various theoretical methods to determine elastic properties of dsDNA of different lengths and base sequences. We also study DNA elasticity in nucleosome core particle (NCP) both in the presence and the absence of salt. We determine stretch modulus and persistence length of short dsDNA and nucleosomal DNA from contour length distribution and bend angle distribution, respectively. For short dsDNA, we find that stretch modulus increases with ionic strength while persistence length decreases. Calculated values of stretch modulus and persistence length for DNA are in quantitative agreement with available experimental data. The trend is opposite for NCP DNA. We find that the presence of histone core makes the DNA stiffer and thus making the persistence length 3-4 times higher than the bare DNA. Similarly, we also find an increase in the stretch modulus for the NCP DNA. Our study for the first time reports the elastic properties of DNA when it is wrapped around the histone core in NCP. We further show that the WLC model is inadequate to describe DNA elasticity at short length scale. Our results provide a deeper understanding of DNA mechanics and the methods are applicable to most protein-DNA complexes.


Assuntos
DNA/química , Elasticidade , Nucleossomos/química , Sequência de Bases , Simulação por Computador
18.
Med Hypotheses ; 83(6): 816-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25468784

RESUMO

Remote ischaemic preconditioning is emerging as a promising clinical technique which can afford immediate protection against coronary ischaemia. The mechanisms which mediate the signal transduction from remote organ to the heart are still unclear. The role of ATP sensitive potassium channels in ischaemic preconditioning has been established. It is known that the red blood cell (RBC) acts as a mediator of local autoregulation in adjusting oxygen supply to demand by sensing hypoxia and releasing ATP locally to achieve vasodilatation in the adjacent vascular beds. Our hypothesis links these two known mechanisms. Remote ischaemic preconditioning and local RBC autoregulation might share a common mechanism using the ATP sensitive potassium channels. Therefore, we hypothesize that the signal transduction by RBC might be partly responsible for this protection against ischaemia.


Assuntos
Eritrócitos/citologia , Precondicionamento Isquêmico Miocárdico/métodos , Isquemia Miocárdica/prevenção & controle , Animais , Humanos , Canais KATP/fisiologia , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Oxigênio/metabolismo , Transdução de Sinais , Vasodilatação
19.
Indian J Endocrinol Metab ; 18(1): 106-10, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24701439

RESUMO

BACKGROUND: The burden of diabetes and its foot complications is increasing in India. Prevention of these complications through foot care education should be explored. The objective of our study was to assess the risk factors of poor diabetic foot care and to find the effectiveness of health education in improving foot care practice among diabetes patients. MATERIALS AND METHODS: A structured pre-tested questionnaire was administered to the outpatients of a rural health center with type 2 diabetes. Awareness regarding diabetes, care of diabetes and foot care practice ware assessed and scored. Individual and group health education focusing on foot care was performed. Foot care practice was reassessed after 2 weeks of education. RESULTS: Only 54% were aware that diabetes could lead to reduced foot sensation and foot ulcers. Nearly 53% and 41% of the patients had good diabetes awareness and good diabetes care respectively. Only 22% of the patients had their feet examined by a health worker or doctor. The patients with poor, satisfactory and good practice scores were 44.7%, 35.9% and 19.4% respectively. Low education status, old age and low awareness regarding diabetes were the risk factors for poor practice of foot care. Average score for practice of foot care improved from 5.90 ± 1.82 to 8.0 ± 1.30 after 2 weeks of health education. Practice related to toe space examination, foot inspection and foot wear inspection improved maximally. CONCLUSION: Foot care education for diabetics in a primary care setting improves their foot care practice and is likely to be effective in reducing the burden of diabetic foot ulcer.

20.
Indian J Public Health ; 57(4): 276-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24351392

RESUMO

Use of Insecticide-Treated Bednets (ITNs) has been shown to reduce the incidence of mosquito-borne diseases. However, the impact of ITNs depends on its community acceptance. We studied the ITN usage and factors influencing it, following the distribution of one ITN to each family in an urban area of Puducherry. Around 93.6% of the 157 respondents surveyed were aware of mosquito-borne diseases. Coils and vaporizers were used in 91.1% of the families. Around two-fifths (41.3%) of the 116 families who received the ITNs used it regularly with another 5.1% using it irregularly. Majority of the users (85%) reported reduced mosquito bites and pleasant sleep after use. Small size of ITNs was the most common reason for non-use (46.3%). Families not using normal bed nets at the time of distribution of ITNs were unlikely to use ITNs at present (odds ratio = 5.22, P < 0.001). Therefore, ITN size should be increased and distribution in urban settings should accompany behavior change communication.


Assuntos
Mosquiteiros Tratados com Inseticida/estatística & dados numéricos , Animais , Estudos Transversais , Feminino , Humanos , Índia , Insetos Vetores , Masculino , Controle de Mosquitos , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA