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1.
Artículo en Inglés | MEDLINE | ID: mdl-38821871

RESUMEN

The state of Uttar Pradesh (UP), India, has one of the largest single public health systems globally, serving about 235 million people through more than 30,000 public health facilities with approximately 160,000 health personnel. Yet, the UP health system has a shortfall of public health facilities to meet the population's needs, a shortage of clinical and nonclinical health personnel, inequitable distribution of existing health personnel, and low utilization of public health facilities. A robust and effective electronic human resource management system (eHRMS) that provides real-time information about the lifecycle of all health professionals in UP may aid in improving the health workforce, resulting in better health services and improved health outcomes. The Government of UP rolled out Manav Sampada, a comprehensive eHRMS that complied with global norms and requirements. We describe the implementation of Manav Sampada at scale and elaborate on key learnings and adoption strategies. Manav Sampada was based on key principles of integration and data-sharing with other digital systems, included functional components, a minimum dataset, used a lifecycle-based approach, and a workflow-based system, all of which acted to improve human resource data quality. The eHRMS emerged as a valuable tool for key stakeholders in reviewing worker performance, identifying skill-building needs, and allocating resources for training, leading to improved availability and equity in the distribution of a few critical cadres. The eHRMS in UP is well positioned to become an integral part of the Ayushman Bharat Digital Mission, the backbone of India's integrated digital health infrastructure. Linking eHRMS to a planned beneficiary-centric unitized health service delivery system (capturing information at the individual level rather than the aggregate level) will enable the measurement of service delivery and quality, leading to improved workforce management.

2.
Chem Biol Interact ; 396: 111027, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38735452

RESUMEN

Antibiotic resistance poses a significant challenge in modern medicine, urging the exploration of innovative approaches to combat bacterial infections. Biofilms, complex bacterial communities encased in a protective matrix, contribute to resistance by impeding antibiotic efficacy and promoting genetic exchange. Understanding biofilm dynamics is crucial for developing effective antimicrobial therapies against antibiotic resistance. This study explores the potential of flavone to combat biofilm-induced antibiotic resistance by employing in-vitro biochemical, cell biology, and Insilico (MD simulation), approaches. Flavone exhibited potent antibacterial effects with a low minimum inhibitory concentration by inducing intracellular reactive oxygen species. Flavones further inhibited the formation of biofilms by 50-60 % and disrupted the pre-formed biofilms by reducing the extracellular polysaccharide substance protective layer formed on the biofilm by 80 %. Quorum sensing (QS) plays a crucial role in bacterial pathogenicity and flavone significantly attenuated the production of QS-induced virulence factors like urease, protease, lipase, hemolysin and prodigiosin pigment in a dose-dependent manner. Further Insilico molecular docking studies along with molecular dynamic simulations run for 100 ns proved the stable binding affinity of flavone with QS-specific proteins which are crucial for biofilm formation. This study demonstrates the therapeutic potential of flavone to target QS-signaling pathway to combat S.marcescens biofilms.


Asunto(s)
Antibacterianos , Biopelículas , Flavonas , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Percepción de Quorum , Biopelículas/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Flavonas/farmacología , Flavonas/química , Antibacterianos/farmacología , Antibacterianos/química , Simulación de Dinámica Molecular , Especies Reactivas de Oxígeno/metabolismo , Farmacorresistencia Microbiana/efectos de los fármacos , Factores de Virulencia/metabolismo , Proteínas Bacterianas/metabolismo
3.
Cell Biochem Biophys ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702575

RESUMEN

In recent decades, the development of novel antimicrobials has significantly slowed due to the emergence of antimicrobial resistance (AMR), intensifying the global struggle against infectious diseases. Microbial populations worldwide rapidly develop resistance due to the widespread use of antibiotics, primarily targeting drug-resistant germs. A prominent manifestation of this resistance is the formation of biofilms, where bacteria create protective layers using signaling pathways such as quorum sensing. In response to this challenge, the CRISPR-Cas9 method has emerged as a ground-breaking strategy to counter biofilms. Initially identified as the "adaptive immune system" of bacteria, CRISPR-Cas9 has evolved into a state-of-the-art genetic engineering tool. Its exceptional precision in altering specific genes across diverse microorganisms positions it as a promising alternative for addressing antibiotic resistance by selectively modifying genes in diverse microorganisms. This comprehensive review concentrates on the historical background, discovery, developmental stages, and distinct components of CRISPR Cas9 technology. Emphasizing its role as a widely used genome engineering tool, the review explores how CRISPR Cas9 can significantly contribute to the targeted disruption of genes responsible for biofilm formation, highlighting its pivotal role in reshaping strategies to combat antibiotic resistance and mitigate the challenges posed by biofilm-associated infectious diseases.

4.
Cureus ; 16(3): e55800, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38586725

RESUMEN

Listeria monocytogenes, a gram-positive bacillus and an intracellular pathogen, is an uncommon cause of illness in the general population. During pregnancy, a perinatal infection can lead to serious complications such as abortion, stillbirth, neonatal sepsis, and meningitis. We present two cases of neonatal meningitis caused by Christie, Atkins, Munch-Peterson (CAMP)-negative Listeria monocytogenes. In the first case, a seven-day-old female term neonate delivered vaginally, presented with high-grade fever and refusal to feed. In view of the suspected late-onset sepsis, a septic workup, including cerebrospinal fluid analysis, was conducted. CSF culture reports obtained showed a growth consistent with Listeria monocytogenes, which was CAMP test negative and susceptible to the penicillin group of drugs, cotrimoxazole, erythromycin, and meropenem. The isolate was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S rRNA sequencing. The blood culture was sterile. At 48 hours of admission, the neonate clinically deteriorated with fluctuation in oxygen saturation below 95% at room air. Thus, she was electively intubated and connected to the mechanical ventilator with appropriate settings. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy. The neonate showed clinical improvement within the next 24 hours of initiating antibiotics according to culture susceptibility and was gradually weaned from the mechanical ventilator to continuous positive airway pressure (CPAP). After 24 hours, she was able to maintain normal saturation at room air. In the second case, an 11-day-old low birth weight neonate, small for gestational age, was presented to the NICU with complaints of loose stools, fever, and refusal to feed for the past two days. In view of the suspected sepsis, relevant investigations were carried out while initiating empirical antibiotics IV piperacillin-tazobactam and IV amikacin for the neonate. Meanwhile, there was a dip in oxygen saturation noted on room air for the neonate and he/she was mechanically ventilated. The CSF culture grew Listeria monocytogenes,which was identified using MALDI-TOF MS and confirmed by 16S rRNA sequencing. The isolate tested negative for the CAMP test and was susceptible to ampicillin, penicillin, cotrimoxazole, erythromycin, and meropenem. The blood culture was sterile. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy, the patient's condition improved, and the baby was eventually discharged.

6.
Curr Biol ; 34(10): 2049-2065.e6, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38677281

RESUMEN

Plants rely on autophagy and membrane trafficking to tolerate stress, combat infections, and maintain cellular homeostasis. However, the molecular interplay between autophagy and membrane trafficking is poorly understood. Using an AI-assisted approach, we identified Rab3GAP-like (Rab3GAPL) as a key membrane trafficking node that controls plant autophagy negatively. Rab3GAPL suppresses autophagy by binding to ATG8, the core autophagy adaptor, and deactivating Rab8a, a small GTPase essential for autophagosome formation and defense-related secretion. Rab3GAPL reduces autophagic flux in three model plant species, suggesting that its negative regulatory role in autophagy is conserved in land plants. Beyond autophagy regulation, Rab3GAPL modulates focal immunity against the oomycete pathogen Phytophthora infestans by preventing defense-related secretion. Altogether, our results suggest that Rab3GAPL acts as a molecular rheostat to coordinate autophagic flux and defense-related secretion by restraining Rab8a-mediated trafficking. This unprecedented interplay between a RabGAP-Rab pair and ATG8 sheds new light on the intricate membrane transport mechanisms underlying plant autophagy and immunity.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Autofagia , Proteínas Activadoras de GTPasa , Inmunidad de la Planta , Autofagia/fisiología , Arabidopsis/inmunología , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/microbiología , Proteínas Activadoras de GTPasa/metabolismo , Proteínas Activadoras de GTPasa/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Familia de las Proteínas 8 Relacionadas con la Autofagia/genética , Phytophthora infestans/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Transporte de Proteínas
7.
Ecol Food Nutr ; 63(3): 229-250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38526225

RESUMEN

This study identified determinants of malnutrition among school children in West Bengal, India. A total of 896 children aged between 4 and 13 years in eight districts were evaluated. BMI, weight, and height-for-age z-scores were used to categorize the stages of malnutrition. The study results revealed that the average height of the boys and girls was as per the standards set by the National Council of Health Sciences. Body mass index of the children ranged between 14.4 and 21.42 kg/m2, and stunting was 56.77%. Age and stunting were positively correlated in 5- to 10-year-old children. The most common deficiency was of fluoride.


Asunto(s)
Estatura , Índice de Masa Corporal , Trastornos del Crecimiento , Humanos , India/epidemiología , Niño , Femenino , Masculino , Preescolar , Adolescente , Trastornos del Crecimiento/epidemiología , Desnutrición/epidemiología , Trastornos de la Nutrición del Niño/epidemiología , Peso Corporal , Fluoruros , Estado Nutricional , Estudios Transversales , Instituciones Académicas
8.
Biomed Mater ; 19(2)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38364289

RESUMEN

Respiratory tract infections (RTIs) are a common cause of mortality and morbidity in the human population. The overuse of antibiotics to overcome such infections has led to antibiotic resistance. The emergence of multidrug resistant bacteria is necessitating the development of novel therapeutic techniques in order to avoid a major global clinical threat. Our study aims to investigate the potential of tryptone stabilised silver nanoparticles (Ts-AgNPs) on planktonic and biofilms produced byKlebsiella pneumoniae(K. pneumoniae)and Pseudomonas aeruginosa(P. aeruginosa). The MIC50of Ts-AgNPs was found to be as low as 1.7 µg ml-1and 2.7 µg ml-1forK. pneumoniae and P.aeruginosarespectively. Ts-AgNPs ability to alter redox environment by producing intracellular ROS, time-kill curves showing substantial decrease in the bacterial growth and significantly reduced colony forming units further validate its antimicrobial effect. The biofilm inhibition and eradication ability of Ts-AgNPs was found to be as high as 93% and 97% in both the tested organisms. A significant decrease in the eDNA and EPS quantity in Ts-AgNPs treated cells proved its ability to successfully distort the matrix and matured biofilms. Interestingly Ts-AgNPs also attenuated QS-induced virulence factors production. This study paves way to develop Ts-AgNPs as novel antibiotics against RTIs causing bacterial biofilms.


Asunto(s)
Nanopartículas del Metal , Peptonas , Infecciones del Sistema Respiratorio , Humanos , Plata/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Biopelículas , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Pseudomonas aeruginosa
9.
Food Sci Technol Int ; : 10820132231188631, 2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37461837

RESUMEN

This study aims to develop a multigrain probiotic biscuit and evaluate the effect of erythritol as a sugar replacer on the rheological properties of dough, along with the physicochemical and organoleptic properties of biscuits. The higher viscoelasticity of dough was observed at a 25% sugar replacement level with erythritol, and the calorific value of biscuits was significantly (p < 0.05) reduced from 415.12 to 404.69 Cal/100 g with increasing in the sugar replacement from 0% to 75%. The biscuits with higher concentrations of erythritol showed reduced water activity (aw) and higher hardness values. From Pearson's correlation analysis, it was observed that the probiotic viability had a positive relation with moisture, fat, energy, aw, and diameter and a negative association with the protein and fiber content of biscuits. The 25% replacement of sugar with erythritol showed a higher probiotic count (> 7 log CFU/g) and improved physicochemical and sensory properties during the storage period, which was further confirmed by the principal component analysis. So, it was recommended that the partial replacement of sugar with erythritol up to 25% is desirable for developing low-calorie bakery products without any alteration in the functional groups and improving the internal structure of the biscuits.

11.
J Biol Inorg Chem ; 28(2): 139-152, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36484825

RESUMEN

Several microbial pathogens are capable of forming biofilms. These microbial communities pose a serious challenge to the healthcare sector as they are quite difficult to combat. Given the challenges associated with the antibiotic-based management of biofilms, the research focus has now been shifted towards finding alternate treatment strategies that can replace or complement the antibacterial properties of antibiotics. The field of nanotechnology offers several novel and revolutionary approaches to eradicate biofilm-forming microbes. In this study, we evaluated the antibacterial and antibiofilm efficacy of in-house synthesized, tryptone-stabilized silver nanoparticles (Ts-AgNPs) against the superbug Serratia marcescens. The nanoparticles were of spherical morphology with an average hydrodynamic diameter of 170 nm and considerable colloidal stability with a Zeta potential of - 24 ± 6.15 mV. Ts-AgNPs showed strong antibacterial activities with a minimum inhibitory concentration (MIC50) of 2.5 µg/mL and minimum bactericidal concentration (MBC) of 12.5 µg/mL against S. marcescens. The nanoparticles altered the cell surface hydrophobicity and inhibited biofilm formation. The Ts-AgNPs were also effective in distorting pre-existing biofilms by degrading the extracellular DNA (eDNA) component of the extracellular polymeric substance (EPS) layer. Furthermore, reduction in quorum-sensing (QS)-induced virulence factors produced by S. marcescens indicated that Ts-AgNPs attenuated the QS pathway. Together, these findings suggest that Ts-AgNPs are an important anti-planktonic and antibiofilm agent that can be explored for both the prevention and treatment of infections caused by S. marcescens.


Asunto(s)
Nanopartículas del Metal , Serratia marcescens , Serratia marcescens/genética , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Matriz Extracelular de Sustancias Poliméricas , Biopelículas , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana
12.
Biol Trace Elem Res ; 201(8): 3791-3803, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36370333

RESUMEN

This study was conducted to evaluate the effect of nano copper (nano Cu) and nano zinc (nano Zn) supplementation on the biomarkers of immunity and antioxidant and health status attributes in young dairy calves. Twenty-four young cattle calves were randomly assigned into four groups (6 calves per group) on a body weight and age basis for a period of 120 days. The feeding regimen was the same in all the groups except that these were supplemented with 0.0 mg nano Cu and nano Zn (control), 10 mg nano Cu (nanoCu10), 32 mg nano Zn (nanoZn32), and a combination of nano Cu and nano Zn (nanoCu10 + nanoZn32) per kg dry matter (DM) basis in four respective groups. Supplementation of nano Cu along with nano Zn improves immune response which was evidenced from higher immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), total immunoglobulin (TIg), and Zn sulphate turbidity (ZST) units and lower plasma concentrations of tumour necrosis factor-α (TNF-α) and cortisol in the nanoCu10 + nanoZn32 group. There was no effect of treatment on the plasma concentrations of immunoglobulin E (IgE) and interferon-gamma (IFN-γ). Antioxidant status was also better in the nanoCu10 + nanoZn32 group as evidenced by lower concentrations of malondialdehyde (MDA) and higher activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), ceruloplasmin (Cp), and total antioxidant status (TAS). However, treatment did not exert any effect on catalase (CAT) activity. Although the nano Cu or nano Zn supplementation, either alone or in combination, did not exert any effect on growth performance or body condition score (BCS), the frequency of diarrhoea and incidence of diarrhoea were lower, while faecal consistency score (FCS) and attitude score were better in the nanoCu10 + nanoZn32 groups. In the control group, one calf was found affected with joint illness and two calves were found affected with navel illness. During the experimental period, none of the calves in all four groups were found to be affected by pneumonia. The findings of this study revealed that dietary supplementation of nano Cu in combination with nano Zn improved the health status of young dairy calves by improving immunity and antioxidant status.


Asunto(s)
Antioxidantes , Nanopartículas del Metal , Animales , Bovinos , Cobre , Zinc/farmacología , Incidencia , Suplementos Dietéticos , Inmunidad , Diarrea , Dieta/veterinaria , Alimentación Animal/análisis
13.
Cureus ; 14(10): e30061, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36381899

RESUMEN

Psoriasis is a chronic, incurable condition with an erratic course of symptoms and triggers by nature. Psoriasis patients need medical attention that extends beyond only treating skin conditions and joint issues. Because psoriasis is so complex, treating it with medication alone does not work well; comprehensive, whole-person treatment is required. Screening for concomitant diseases including hypertension, dyslipidemia, diabetes mellitus, cardiovascular issues, and their adverse effects like myocardial infarction and stroke is a part of treating psoriasis. Regular screening for these linked illnesses should be done. Essential elements of psoriasis care include co-medication to avoid drug interactions or drug-induced psoriasis, as well as the identification and management of trigger factors. The lack of widely used and established diagnostic criteria restricts these studies. Essential elements of psoriasis management include routine screening for these associated disorders, co-medication to avoid drug interactions or psoriasis caused by drugs, as well as the identification of trigger factors and their management. This short review highlights the effectiveness of dialysis in people with psoriasis and the fact that the benefit is more pronounced with peritoneal dialysis than with hemodialysis.

14.
Trop Med Infect Dis ; 7(9)2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36136655

RESUMEN

BACKGROUND: Drug-resistant tuberculosis is a major public health problem throughout the world and accounts for substantial morbidity and mortality rates in India, too. Early diagnosis is the corner stone of tuberculosis treatment. State-level and cluster-wise variations in drug resistance is a possibility and should be regularly checked in from time to time. MATERIALS AND METHODS: The present prospective cohort study (January 2019 to May 2022) was conducted in Darbhanga Medical College and Hospital on drug-resistant pulmonary tuberculosis patients. Sputum specimens were collected from designated centers. Rapid molecular drug-resistance testing (genotypic tests) and growth-based drug-susceptibility testing (DST) (phenotypic tests) were performed in the National Tuberculosis Elimination Program certified Laboratory. RESULTS: A total of 268 patients with drug-resistant pulmonary tuberculosis were included in the study group. The treatment outcomes revealed as cured in 100 (37.31%); treatment completed in 43 (16.04%); died in 56 (20.89%); treatment failed in 22 (8.21%); loss of follow up in 34 (12.69%); and transferred out in 13 (4.85%) drug-resistant pulmonary tuberculosis patients. Adverse events were recorded in 199 (74.25%) of the drug-resistant pulmonary tuberculosis patients. CONCLUSIONS: Drug-resistant pulmonary tuberculosis patients are a matter of concern and need to be addressed.

15.
EMBO J ; 41(13): e110352, 2022 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-35620914

RESUMEN

Beyond its role in cellular homeostasis, autophagy plays anti- and promicrobial roles in host-microbe interactions, both in animals and plants. One prominent role of antimicrobial autophagy is to degrade intracellular pathogens or microbial molecules, in a process termed xenophagy. Consequently, microbes evolved mechanisms to hijack or modulate autophagy to escape elimination. Although well-described in animals, the extent to which xenophagy contributes to plant-bacteria interactions remains unknown. Here, we provide evidence that Xanthomonas campestris pv. vesicatoria (Xcv) suppresses host autophagy by utilizing type-III effector XopL. XopL interacts with and degrades the autophagy component SH3P2 via its E3 ligase activity to promote infection. Intriguingly, XopL is targeted for degradation by defense-related selective autophagy mediated by NBR1/Joka2, revealing a complex antagonistic interplay between XopL and the host autophagy machinery. Our results implicate plant antimicrobial autophagy in the depletion of a bacterial virulence factor and unravel an unprecedented pathogen strategy to counteract defense-related autophagy in plant-bacteria interactions.


Asunto(s)
Enfermedades de las Plantas , Factores de Virulencia , Animales , Autofagia , Bacterias/metabolismo , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/microbiología , Factores de Virulencia/genética , Factores de Virulencia/metabolismo
16.
J Food Sci Technol ; 59(4): 1637-1648, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35250087

RESUMEN

A grain based carbonated beverage premix with adequate nutritional composition and fizzing effect in the form of dry powder has been developed in the current study. Maize and Bengal gram were roasted at temperature 160-180 °C while finger millet at 80-120 °C for 10-30 min. The optimized conditions for the roasting of maize, Bengal gram and finger millet were 180 °C for 10 min, 180 °C for 27 min and 110 °C for 30 min, respectively using face centred composite design and response surface methodology (RSM). The formulation of the beverage premix obtained using linear programming was in the proportion of 30 g, 30 g, 10 g, 20 g and 10 g of roasted maize, Bengal gram, finger millet flours, sugar (powdered) and pea protein isolate, respectively. The effect of carbonation was found to be best with 8% carbonation powder concentration and 1:4 beverage premix to water ratio which showed an overall acceptability of 7.7. The developed carbonated beverage premix was light in color with a positive L* value of 79.01 ± 0.12 and slightly acidic with a pH of 5.56 ± 0.10. The nutritional composition of the final product comprised of 16% protein and several minerals viz. Fe (11.67 mg/100 g), Ca (36.67 mg/100 g) and Mg (86.26 mg/100 g). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05175-5.

17.
Food Bioproc Tech ; 15(5): 998-1039, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35126801

RESUMEN

From the past few decades, consumers' demand for probiotic-based functional and healthy food products is rising exponentially. Encapsulation is an emerging field to protect probiotics from unfavorable conditions and to deliver probiotics at the target place while maintaining the controlled release in the colon. Probiotics have been encapsulated for decades using different encapsulation methods to maintain their viability during processing, storage, and digestion and to give health benefits. This review focuses on novel microencapsulation techniques of probiotic bacteria including vacuum drying, microwave drying, spray freeze drying, fluidized bed drying, impinging aerosol technology, hybridization system, ultrasonication with their recent advancement, and characteristics of the commonly used polymers have been briefly discussed. Other than novel techniques, characterization of microcapsules along with their mechanism of release and stability have shown great interest recently in developing novel functional food products with synergetic effects, especially in COVID-19 outbreak. A thorough discussion of novel processing technologies and applications in food products with the incorporation of recent research works is the novelty and highlight of this review paper.

18.
BMC Health Serv Res ; 21(1): 1027, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34587959

RESUMEN

BACKGROUND: In India, the distribution and retention of biomedical doctors in public sector facilities in rural areas is an obstacle to improving access to health services. The Government of Uttar Pradesh is developing a comprehensive, ten-year Human Resources for Health (HRH) strategy, which includes policies to address rural distribution and retention of government doctors in Uttar Pradesh (UP). We undertook a stakeholder analysis to understand stakeholder positions on particular policies within the strategy, and to examine how stakeholder power and interests would shape the development and implementation of these proposed policies. This paper focuses on the results of the stakeholder analysis pertaining to rural distribution and retention of doctors in the government sector in UP. Our objectives are to 1) analyze stakeholder power in influencing the adoption of policies; 2) compare and analyze stakeholder positions on specific policies, including their perspectives on the conditions for successful policy adoption and implementation; and 3) explore the challenges with developing and implementing a coordinated, 'bundled' approach to strengthening rural distribution and retention of doctors. METHODS: We utilized three forms of data collection for this study - document review, in-depth interviews and focus group discussions. We conducted 17 interviews and three focus group discussions with key stakeholders between September and November 2019. RESULTS: We found that the adoption of a coordinated policy approach for rural retention and distribution of doctors is negatively impacted by governance challenges and fragmentation within and beyond the health sector. Respondents also noted that the opposition to certain policies by health worker associations created challenges for comprehensive policy development. Finally, respondents believed that even in the event of policy adoption, implementation remained severely hampered by several factors, including weak mechanisms of accountability and perceived corruption at local, district and state level. CONCLUSION: Building on the findings of this analysis, we propose several strategies for addressing the challenges in improving access to government doctors in rural areas of UP, including additional policies that address key concerns raised by stakeholders, and improved mechanisms for coordination, accountability and transparency.


Asunto(s)
Médicos , Servicios de Salud Rural , Humanos , India , Políticas , Recursos Humanos
19.
Elife ; 102021 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-34424198

RESUMEN

Eukaryotic cells deploy autophagy to eliminate invading microbes. In turn, pathogens have evolved effector proteins to counteract antimicrobial autophagy. How adapted pathogens co-opt autophagy for their own benefit is poorly understood. The Irish famine pathogen Phytophthora infestans secretes the effector protein PexRD54 that selectively activates an unknown plant autophagy pathway that antagonizes antimicrobial autophagy at the pathogen interface. Here, we show that PexRD54 induces autophagosome formation by bridging vesicles decorated by the small GTPase Rab8a with autophagic compartments labeled by the core autophagy protein ATG8CL. Rab8a is required for pathogen-triggered and starvation-induced but not antimicrobial autophagy, revealing specific trafficking pathways underpin selective autophagy. By subverting Rab8a-mediated vesicle trafficking, PexRD54 utilizes lipid droplets to facilitate biogenesis of autophagosomes diverted to pathogen feeding sites. Altogether, we show that PexRD54 mimics starvation-induced autophagy to subvert endomembrane trafficking at the host-pathogen interface, revealing how effectors bridge distinct host compartments to expedite colonization.


With its long filaments reaching deep inside its prey, the tiny fungi-like organism known as Phytophthora infestans has had a disproportionate impact on human history. Latching onto plants and feeding on their cells, it has caused large-scale starvation events such as the Irish or Highland potato famines. Many specialized proteins allow the parasite to accomplish its feat. For instance, PexRD54 helps P. infestans hijack a cellular process known as autophagy. Healthy cells use this 'self-eating' mechanism to break down invaders or to recycle their components, for example when they require specific nutrients. The process is set in motion by various pathways of molecular events that result in specific sac-like 'vesicles' filled with cargo being transported to specialized compartments for recycling. PexRD54 can take over this mechanism by activating one of the plant autophagy pathways, directing cells to form autophagic vesicles that Phytophthora could then possibly use to feed on or to destroy antimicrobial components. How or why this is the case remains poorly understood. To examine these questions, Pandey, Leary et al. used a combination of genetic and microscopy techniques and tracked how PexRD54 alters autophagy as P. infestans infects a tobacco-related plant. The results show that PexRD54 works by bridging two proteins: one is present on cellular vesicles filled with cargo, and the other on autophagic structures surrounding the parasite. This allows PexRD54 to direct the vesicles to the feeding sites of P. infestans so the parasite can potentially divert nutrients. Pandey, Leary et al. then went on to develop a molecule called the AIM peptide, which could block autophagy by mimicking part of PexRD54. These results help to better grasp how a key disease affects crops, potentially leading to new ways to protect plants without the use of pesticides. They also shed light on autophagy: ultimately, a deeper understanding of this fundamental biological process could allow the development of plants which can adapt to changing environments.


Asunto(s)
Proteínas Fúngicas/genética , Interacciones Huésped-Patógeno , Phytophthora infestans/fisiología , Proteínas de Plantas/genética , Solanum tuberosum/genética , Autofagia , Proteínas Fúngicas/metabolismo , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Solanum tuberosum/metabolismo , Solanum tuberosum/microbiología
20.
Plant J ; 107(6): 1771-1787, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34250673

RESUMEN

Upon immune activation, chloroplasts switch off photosynthesis, produce antimicrobial compounds and associate with the nucleus through tubular extensions called stromules. Although it is well established that chloroplasts alter their position in response to light, little is known about the dynamics of chloroplast movement in response to pathogen attack. Here, we report that during infection with the Irish potato famine pathogen Phytophthora infestans, chloroplasts accumulate at the pathogen interface, associating with the specialized membrane that engulfs the pathogen haustorium. The chemical inhibition of actin polymerization reduces the accumulation of chloroplasts at pathogen haustoria, suggesting that this process is partially dependent on the actin cytoskeleton. However, chloroplast accumulation at haustoria does not necessarily rely on movement of the nucleus to this interface and is not affected by light conditions. Stromules are typically induced during infection, embracing haustoria and facilitating chloroplast interactions, to form dynamic organelle clusters. We found that infection-triggered stromule formation relies on BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1)-mediated surface immune signaling, whereas chloroplast repositioning towards haustoria does not. Consistent with the defense-related induction of stromules, effector-mediated suppression of BAK1-mediated immune signaling reduced stromule formation during infection. On the other hand, immune recognition of the same effector stimulated stromules, presumably via a different pathway. These findings implicate chloroplasts in a polarized response upon pathogen attack and point to more complex functions of these organelles in plant-pathogen interactions.


Asunto(s)
Cloroplastos/microbiología , Interacciones Huésped-Patógeno/fisiología , Nicotiana/microbiología , Phytophthora infestans/patogenicidad , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/microbiología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cloroplastos/efectos de los fármacos , Cloroplastos/inmunología , Dinitrobencenos/farmacología , Luz , Microscopía Confocal , Pinzas Ópticas , Enfermedades de las Plantas/microbiología , Inmunidad de la Planta , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/microbiología , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno/metabolismo , Sulfanilamidas/farmacología , Tiazolidinas/farmacología , Nicotiana/efectos de los fármacos , Nicotiana/genética , Nicotiana/inmunología
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