ULK1 and ULK2 Regulate Stress Granule Disassembly Through Phosphorylation and Activation of VCP/p97.

Disturbances in autophagy and stress granule dynamics have been implicated as potential mechanisms underlying inclusion body myopathy (IBM) and related disorders. Yet the roles of core autophagy proteins in IBM and stress granule dynamics remain poorly characterized. Here, we demonstrate that disrupted expression of the core autophagy proteins ULK1 and ULK2 in mice causes a vacuolar myopathy with ubiquitin and TDP-43-positive inclusions; this myopathy is similar to that caused by VCP/p97 mutations, the most common cause of familial IBM. Mechanistically, we show that ULK1/2 localize to stress granules and phosphorylate VCP, thereby increasing VCP's activity and ability to disassemble stress granules. These data suggest that VCP dysregulation and defective stress granule disassembly contribute to IBM-like disease in Ulk1/2-deficient mice. In addition, stress granule disassembly is accelerated by an ULK1/2 agonist, suggesting ULK1/2 as targets for exploiting the higher-order regulation of stress granules for therapeutic intervention of IBM and related disorders.

The orally bioavailable GSPT1/2 degrader SJ6986 exhibits in vivo efficacy in acute lymphoblastic leukemia.

Advancing cure rates for high-risk acute lymphoblastic leukemia (ALL) has been limited by the lack of agents that effectively kill leukemic cells, sparing normal hematopoietic tissue. Molecular glues direct the ubiquitin ligase cellular machinery to target neosubstrates for protein degradation. We developed a novel cereblon modulator, SJ6986, that exhibits potent and selective degradation of GSPT1 and GSPT2 and cytotoxic activity against childhood cancer cell lines. Here, we report in vitro and in vivo testing of the activity of this agent in a panel of ALL cell lines and xenografts. SJ6986 exhibited similar cytotoxicity to the previously described GSPT1 degrader CC-90009 in a panel of leukemia cell lines in vitro, resulting in apoptosis and perturbation of cell cycle progression. SJ6986 was more effective than CC-90009 in suppressing leukemic cell growth in vivo, partly attributable to favorable pharmacokinetic properties, and did not significantly impair differentiation of human CD34+ cells ex vivo. Genome-wide CRISPR/Cas9 screening of ALL cell lines treated with SJ6986 confirmed that components of the CRL4CRBN complex, associated adaptors, regulators, and effectors were integral in mediating the action of SJ6986. SJ6986 is a potent, selective, orally bioavailable GSPT1/2 degrader that shows broad antileukemic activity and has potential for clinical development.

A Prospective Questionnaire-Based Study Evaluating Genetic Literacy and Impact of Brief Educational Intervention Among Breast Cancer Patients in a Low- to Middle-Income Country.

INTRODUCTION: A significant proportion of breast cancer cases are hereditary and are potentially preventable. However, adoption of the preventive measures remains a significant challenge, particularly because of to lack of knowledge and awareness in low- to middle-income countries. METHODS: This prospective study conducted at a high-volume tertiary care cancer center in North India to assess the knowledge, awareness, and attitudes of female breast cancer patients and impact of a brief educational intervention. The study involved three phases: pre-interventional assessment, educational intervention, and post-interventional assessment utilizing a structured questionnaire. RESULTS: The study involved 300 newly diagnosed breast cancer patients; 16.7% were familial. At the outset, 87.0% patients had low knowledge of risk factors, 90.3% about screening, and 32.7% about treatment. Awareness levels were low: 13.7% aware of familial risk and 2.7% of breast cancer genes. Affordability of genetic testing was low (15.2%), and interest in testing for self and family members was limited (32.0% and 26.3%). Following educational intervention, a significant positive percentage change was noticed in knowledge (risk factors: 12.8%, screening: 36.2%, treatment: 82%), awareness (familial risk: 66.7%, BRCA gene: 12.3%), and attitude (testing for self: 17.8%, family: 19.5%). CONCLUSIONS: This study highlights the significant knowledge gaps among breast cancer patients regarding genetics. The educational intervention led to notable improvements in knowledge, awareness, and attitudes, underscoring the importance of tailored patient education in breast cancer care.

Tuning the Flavin Core via Donor Appendage for Selective Subcellular Bioimaging and PDT Application.

Herein, we report a novel flavin analogue as singular chemical component for lysosome bioimaging, and inherited photosensitizer capability of the flavin core was demonstrated as a promising candidate for photodynamic therapy (PDT) application. Fine-tuning the flavin core with the incorporation of methoxy naphthyl appendage provides an appropriate chemical design, thereby offering photostability, selectivity, and lysosomal colocalization, along with the aggregation-induced emissive nature, making it suitable for lysosomal bioimaging applications. Additionally, photosensitization capability of the flavin core with photostable nature of the synthesized analogue has shown remarkable capacity for generating reactive oxygen species (ROS) within cells, making it a promising candidate for photodynamic therapy (PDT) application.

Metal-Free Direct C3-H Alkylation and Arylation of Quinoxalin-2(1H)-Ones with Inert Alkyl and Aryl Chlorides.

In the present manuscript, we reported the first visible-light-enabled direct C3-H alkylation/arylation of quinoxalin-2(1H)-ones with unactivated alkyl/aryl chlorides under metal-free conditions. A wide range of unactivated alkyl and aryl chlorides containing different functionalities are coupled with a variety of quinoxalin-2(1H)-one derivatives under mild reaction conditions to afford the C3-alkyl/aryl substituted quinoxalin-2(1H)-ones in moderate to good yields.

Flavin based supramolecular gel displaying multi-stimuli triggered sol-gel transition.

Herein, we report the design and synthesis of an amphiphilic flavin analogue as a robust low molecular weight gelator involving minimal structural modification. Four flavin analogues were evaluated for their gelation capabilities and the flavin analogue with antipodal positioning of the carboxyl and octyl functionalities was found to be the most efficient gelator with the minimum gelation concentration being as low as 0.03 M. A wide range of solvents were used for gelation studies suggesting its widespread applicability. Morphological, photophysical and rheological characterization studies were performed to fully characterize the nature of the gel. Interestingly, reversible multiple stimuli responsive sol-gel transition was observed with changing pH and redox activity, while metal screening showed specific transition in the presence of ferric ions. The gel was able to differentiate between ferric and ferrous species with well-defined sol-gel transition. The current results potentially offer a redox-active flavin-based material as a low molecular weight gelator for the development of next-generation materials.

Stabilizing hydroperoxyflavin intermediate formation via a peptide appendage: a neutral flavoenzyme model.

A bioinspired mimic for the stabilization of hydroperoxyflavin intermediate formation was designed and investigated for monooxygenase like catalytic properties. A suitable peptide appendage was covalently linked to the C7-position of the neutral isoalloxazine core to synthesize Fl-G, Fl-F, Fl-P, and Fl-ßA analogues. While the presence and identity of the peptide appendage were found to be crucial for catalytic efficiency, corroborative observations were made from theoretical studies as well, supporting the precise conformational and accessibility requirements for the stabilization of the key hydroperoxyflavin intermediate. A simple yet elegant flavopeptide model (Fl-G) was found to achieve almost quantitative catalytic efficiency compared to the control flavin analogue without a peptide appendage.

No Doppler Single Position-Lateral Intercostal Artery Perforator Flap (NDSP-LICAP): a Safe and Versatile Flap for Breast Oncoplasty in Resource-Limited Setting.

INTRODUCTION: The lateral intercostal artery perforator flap (LICAP) has emerged as one of the safest and less morbid flaps for lateral and central breast defects. We hereby describe a reproducible no Doppler single position (NDSP) technique to harvest it in single position without handheld Doppler, making it a versatile flap for lateral breast defects in resource-limited setting also. MATERIALS AND METHODS: With this technique, we performed a total of 22 LICAP turnover flaps over a period of 18 months from January 2020 to June 2021. In all 22 cases, the indication of flap was to fill the post-breast conservation surgery (BCS) defects in outer quadrant of breast. All LICAP flaps were harvested by surface marking of anatomical landmarks and without handheld Doppler. RESULTS: Out of 22 LICAP turnover flaps, thirteen were harvested for left breast and nine for right breast. The median width and length of the flap were 12.2 cm and 19.6 cm, respectively. The additional mean operative time was 41 min. All LICAP flaps survived well, and grade 1 Clavien-Dindo morbidity was documented in four cases. Mean hospital stay was 2.6 days. All patients received radiotherapy on their stipulated schedule. Early cosmetic outcome was good, and long-term outcomes are awaited. CONCLUSION: NDSP-LICAP flap is a workhorse for lateral breast defects. Precise knowledge of perforators and anatomical landmarks can be used for harvesting these flaps, thus avoiding ultrasound Doppler and dedicated training for perforator localization. This technique has short learning curve without the need for any plastic surgery training. The early cosmetic outcomes are good.

Luminescence and morphological behaviour of the aromatic dipeptide pair having singular structural variability.

In the present manuscript, the luminescence and the self-assembly behaviour of two aromatic dipeptides with a singular structure variable are investigated. The terminally protected dipeptides tryptophan-tyrosine (WYp ) and tryptophan-phenylalanine (WFp ) were synthesized using a standard solution phase procedure. Significant solvatochromic effect was observed for both the dipeptidyl entities; whilst the influence was more pronounced for the WYp entity when compared with WFp . Interesting morphological variation was observed for WFp and WYp , in which discrete and interconnected nanospheres were observed for the respective dipeptides. The results obtained signify the influence of the singular structural variation on modulating the overall functional behaviour of the short peptides motifs.

Investigating the spectral and electrochemical properties of novel flavin-pyrene dyads separated via variable spacer.

The present manuscript describes the synthesis and the photophysical properties of a pair of novel flavin-pyrene dyads where the donor and the acceptor entities are separated via variable spacer. The dyads were well characterized using standard techniques and investigated for their photophysical and electrochemical nature. The observed absorption spectra of the dyads mainly display peaks corresponding to the individual pyrene and flavin units, with some contribution from the flavin entity in the pyrene region. While, strong emission quenching was observed for both the dyads if compared to its individual constituents. However, a careful analysis of the emission spectra and the solvent dependent studies reveals subtle difference between the two dyads. While no significant difference could be observed when excited in the flavin region; excitation at the pyrene region displays a weak and broad emission band in case of closely connected dyad. Further, the electrochemical properties were investigated by cyclic voltammetry and the reduction ability was observed to follow the trend as FlPy2 < FlPy1 < Fl.

A Comprehensive Survey on Multi-Agent Reinforcement Learning for Connected and Automated Vehicles.

Connected and automated vehicles (CAVs) require multiple tasks in their seamless maneuverings. Some essential tasks that require simultaneous management and actions are motion planning, traffic prediction, traffic intersection management, etc. A few of them are complex in nature. Multi-agent reinforcement learning (MARL) can solve complex problems involving simultaneous controls. Recently, many researchers applied MARL in such applications. However, there is a lack of extensive surveys on the ongoing research to identify the current problems, proposed methods, and future research directions in MARL for CAVs. This paper provides a comprehensive survey on MARL for CAVs. A classification-based paper analysis is performed to identify the current developments and highlight the various existing research directions. Finally, the challenges in current works are discussed, and some potential areas are given for exploration to overcome those challenges. Future readers will benefit from this survey and can apply the ideas and findings in their research to solve complex problems.

Evaluation of Growth Responses of Lettuce and Energy Efficiency of the Substrate and Smart Hydroponics Cropping System.

Smart sensing devices enabled hydroponics, a concept of vertical farming that involves soilless technology that increases green area. Although the cultivation medium is water, hydroponic cultivation uses 13 ± 10 times less water and gives 10 ± 5 times better quality products compared with those obtained through the substrate cultivation medium. The use of smart sensing devices helps in continuous real-time monitoring of the nutrient requirements and the environmental conditions required by the crop selected for cultivation. This, in turn, helps in enhanced year-round agricultural production. In this study, lettuce, a leafy crop, is cultivated with the Nutrient Film Technique (NFT) setup of hydroponics, and the growth results are compared with cultivation in a substrate medium. The leaf growth was analyzed in terms of cultivation cycle, leaf length, leaf perimeter, and leaf count in both cultivation methods, where hydroponics outperformed substrate cultivation. The results of the 'AquaCrop simulator also showed similar results, not only qualitatively and quantitatively, but also in terms of sustainable growth and year-round production. The energy consumption of both the cultivation methods is compared, and it is found that hydroponics consumes 70 ± 11 times more energy compared to substrate cultivation. Finally, it is concluded that smart sensing devices form the backbone of precision agriculture, thereby multiplying crop yield by real-time monitoring of the agronomical variables.

Dynamics of Neural Microstates in the VTA-Striatal-Prefrontal Loop during Novelty Exploration in the Rat.

Neural activity at the large-scale population level has been suggested to be consistent with a sequence of brief, quasistable spatial patterns. These "microstates" and their temporal dynamics have been linked to myriad cognitive functions and brain diseases. Most of this research has been performed using EEG, leaving many questions, such as the existence, dynamics, and behavioral relevance of microstates at the level of local field potentials (LFPs), unaddressed. Here, we adapted the standard EEG microstate analysis to triple-area LFP recordings from 192 electrodes in rats to investigate the mesoscopic dynamics of neural microstates within and across brain regions during novelty exploration. We performed simultaneous recordings from the prefrontal cortex, striatum, and ventral tegmental area in male rats during awake behavior (object novelty and exploration). We found that the LFP data can be accounted for by multiple, recurring microstates that were stable for ∼60-100 ms. The simultaneous microstate activity across brain regions revealed rhythmic patterns of coactivations, which we interpret as a novel indicator of inter-regional, mesoscale synchronization. Furthermore, these rhythmic coactivation patterns across microstates were modulated by behavioral states such as movement and exploration of a novel object. These results support the existence of a functional mesoscopic organization across multiple brain areas and present a possible link of the origin of macroscopic EEG microstates to zero-lag neuronal synchronization within and between brain areas, which is of particular interest to the human research community.SIGNIFICANCE STATEMENT The coordination of neural activity across the entire brain has remained elusive. Here we combine large-scale neural recordings at fine spatial resolution with the analysis of microstates (i.e., short-lived, recurring spatial patterns of neural activity). We demonstrate that the local activity in different brain areas can be accounted for by only a few microstates per region. These microstates exhibited temporal dynamics that were correlated across regions in rhythmic patterns. We demonstrate that these microstates are linked to behavior and exhibit different properties in the frequency domain during different behavioral states. In summary, LFP microstates provide an insightful approach to studying both mesoscopic and large-scale brain activation within and across regions.

Intra- and inter-regional dynamics in cortical-striatal-tegmental networks.

It is increasingly recognized that networks of brain areas work together to accomplish computational goals. However, functional connectivity networks are not often compared between different behavioral states and across different frequencies of electrical oscillatory signals. In addition, connectivity is always defined as the strength of signal relatedness between two atlas-based anatomical locations. Here, we performed an exploratory analysis using data collected from high-density arrays in the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA) of male rats. These areas have all been implicated in a wide range of different tasks and computations including various types of memory as well as reward valuation, habit formation and execution, and skill learning. Novel intraregional clustering analyses identified patterns of spatially restricted, temporally coherent, and frequency-specific signals that were reproducible across days and were modulated by behavioral states. Multiple clusters were identified within each anatomical region, indicating a mesoscopic scale of organization. Generalized eigendecomposition (GED) was used to dimension-reduce each cluster to a single component time series. Dense intercluster connectivity was modulated by behavioral state, with connectivity becoming reduced when the animals were exposed to a novel object, compared with a baseline condition. Behavior-modulated connectivity changes were seen across the spectrum, with δ, θ, and γ all being modulated. These results demonstrate the brain's ability to reorganize functionally at both the intra- and inter-regional levels during different behavioral states.NEW & NOTEWORTHY We applied novel clustering techniques to discover functional subregional anatomical patches that changed with behavioral conditions but were frequency specific and stable across days. By taking into account these changes in intraregional signal generator location and extent, we were able to reveal a richer picture of inter-regional functional connectivity than would otherwise have been possible. These findings reveal that the brain's functional organization changes with state at multiple levels of scale.

In-Cabin Monitoring System for Autonomous Vehicles.

In this paper, we have demonstrated a robust in-cabin monitoring system (IMS) for safety, security, surveillance, and monitoring, including privacy concerns for personal and shared autonomous vehicles (AVs). It consists of a set of monitoring cameras and an onboard device (OBD) equipped with artificial intelligence (AI). Hereafter, this combination of a camera and an OBD is referred to as the AI camera. We have investigated the issues for mobility services in higher levels of autonomous driving, what needs to be monitored, how to monitor, etc. Our proposed IMS is an on-device AI system that indigenously has improved the privacy of the users. Furthermore, we have enlisted the essential actions to be considered in an IMS and developed an appropriate database (DB). Our DB consists of multifaced scenarios important for monitoring the in-cabin of the higher-level AVs. Moreover, we have compared popular AI models applied for object and occupant recognition. In addition, our DB is available on request to support the research on the development of seamless monitoring of the in-cabin higher levels of autonomous driving for the assurance of safety and security.

Modeling of the As (III) adsorption using Fe impregnated polyethylene terephthalate char matrix: A statistical approach.

The present research aimed to analyse the impact of economical Fe impregnated polyethylene terephthalate (PET) char (PETC-Fe) for adsorption of As (III) through series of column experiments. For an inlet arsenite concentration of 1,000 µg/L, PETC-Fe exhibits excellent uptake capacity of 1,892 µg/g. Central composite design (CCD) in response surface methodology (RSM) was used to evaluate the influence of various process variables on the response function (breakthrough time) for optimization and assessment of interaction effects. The breakthrough time is more responsive to influent As (III) concentration and bed height than inlet flow rate, according to the perturbation plot. Adams-Bohart, Bed Depth Service Time (BDST) model, and Thomas models were used to model the dynamics of the adsorption system. The BDST model suited the experimental data well in the early part of the breakthrough curve, but there were minor variations over the breakpoints. Despite the fact that the experimental values and the data sets estimated using the Adams-Bohart model followed a similar pattern, they differed slightly. The PETC-Fe was found to be a sustainable and highly economical adsorbent, with a desorption performance of more than 97%, indicating the adsorbent's reusability. This adsorbent's excellent As (III) uptake capacity and regeneration performance imply that it might be used in industrial/domestic applications, and the information obtained could aid in future scaling up of the adsorption system.

Stop codon read-through of mammalian MTCH2 leading to an unstable isoform regulates mitochondrial membrane potential.

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through-deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

Authorized Traffic Controller Hand Gesture Recognition for Situation-Aware Autonomous Driving.

An authorized traffic controller (ATC) has the highest priority for direct road traffic. In some irregular situations, the ATC supersedes other traffic control. Human drivers indigenously understand such situations and tend to follow the ATC; however, an autonomous vehicle (AV) can become confused in such circumstances. Therefore, autonomous driving (AD) crucially requires a human-level understanding of situation-aware traffic gesture recognition. In AVs, vision-based recognition is particularly desirable because of its suitability; however, such recognition systems have various bottlenecks, such as failing to recognize other humans on the road, identifying a variety of ATCs, and gloves in the hands of ATCs. We propose a situation-aware traffic control hand-gesture recognition system, which includes ATC detection and gesture recognition. Three-dimensional (3D) hand model-based gesture recognition is used to mitigate the problem associated with gloves. Our database contains separate training and test videos of approximately 60 min length, captured at a frame rate of 24 frames per second. It has 35,291 different frames that belong to traffic control hand gestures. Our approach correctly recognized traffic control hand gestures; therefore, the proposed system can be considered as an extension of the operational domain of the AV.

EEG microstates as a continuous phenomenon.

In recent years, EEG microstate analysis has gained popularity as a tool to characterize spatio-temporal dynamics of large-scale electrophysiology data. It has been used in a wide range of EEG studies and the discovered microstates have been linked to cognitive function and brain diseases. EEG microstates are assumed to (1) be winner-take-all, meaning that the topography at any given time point is in one state; and (2) discretely transition from one state into another. In this study we investigated these assumptions by taking a geometric perspective of EEG data, treating microstate topographies as basis vectors for a subspace of the original channel space. We found that within- and across-microstate distance distributions were largely overlapping: for the low GFP (Global Field Power) range (lower 15%), individual time points labeled as one microstate are often equidistant to multiple microstate vectors, challenging the winner-take-all assumption. At high global field power, separability of microstates improved, but remained rather weak. Although many GFP peaks (which are the time points used for defining microstates) occur during high GFP ranges, low GFP ranges associated with poor separability also contain GFP peaks. Furthermore, the geometric analysis suggested that microstates and their transitions appear to be more continuous than discrete. The Analysis of rate of change of trajectory in sensor space suggests gradual microstate transitions as opposed to the classical binary view of EEG microstates. Taken together, our findings suggest that EEG microstates are better conceptualized as spatially and temporally continuous, rather than discrete activations of neural populations.

'Know-Can' gap: gap between knowledge and skills related to childhood diarrhoea and pneumonia among frontline workers in rural Uttar Pradesh, India.

OBJECTIVES: In India, frontline workers (FLWs) - public accredited social health activists (ASHAs) and private rural medical providers (RMPs) - are important for early detection and treatment of childhood diarrhoea and pneumonia. This cross-sectional study aims to measure knowledge and skills, and the gap between the two ('know-can' gap), regarding assessment of childhood diarrhoea with dehydration and pneumonia among FLWs, and to explore factors associated with them. METHODS: We surveyed 473 ASHAs and 447 RMPs in six districts of Uttar Pradesh. We assessed knowledge and skills using face-to-face interviews and video vignettes, respectively, about key signs of both conditions. The 'know-can' gap corresponds to absent skills among FLWs with correct knowledge. We used logistic regression to identify the correlates of knowledge and skills. RESULTS: FLWs' correct knowledge ranged from 23% to 48% for dehydration signs and 27% to 37% for pneumonia signs. Their skills ranged from 3% to 42% for dehydration and 3% to 18% for pneumonia. There was a significant 'know-can' gap in all the signs, except 'sunken eyes'. Training and supervisory support was associated with better knowledge and skills for diarrhoea with dehydration, but only better knowledge for pneumonia. CONCLUSIONS: FLWs are crucial to the Indian health system, and high-quality FLW services are necessary for continued progress against under-five deaths. The gap between FLWs' knowledge and skills warrants immediate attention. In particular, our results suggest that knowledge-focused trainings are insufficient for FLWs to convert knowledge into appropriate assessment skills.

OBJECTIFS: En Inde, les travailleurs de première ligne (TPL) - activistes de la santé sociale accrédités par le public (ASSAP) et prestataires médicaux ruraux privés (PMRP) - sont importants pour la détection et le traitement précoces de la diarrhée et de la pneumonie infantiles. Cette étude transversale vise à mesurer les connaissances et les compétences, et l'écart entre les deux (écart ''savoir-pouvoir''), en ce qui concerne l'évaluation de la diarrhée infantile avec déshydratation et la pneumonie chez les TPL et à explorer les facteurs qui leur sont associés. MÉTHODES: Nous avons mené une enquête sur 473 ASSAP et 447 PMRP dans six districts de l'Uttar Pradesh. Nous avons évalué les connaissances et les compétences à l'aide d'entretiens de face à face et de vignettes vidéo, respectivement, sur les signes clés des deux conditions. L'écart «savoir-pouvoir¼ correspond à des compétences absentes parmi les TPL ayant des connaissances correctes. Nous avons utilisé la régression logistique pour identifier les corrélats des connaissances et des compétences. RÉSULTATS: Les connaissances correctes des TPL variaient de 23% à 48% pour les signes de déshydratation, 27% à 37% pour les signes de pneumonie. Leurs compétences variaient de 3% à 42% pour la déshydratation et de 3% à 18% pour la pneumonie. Il y avait un écart important dans le «savoir-pouvoir¼ pour tous les signes, à l'exception des «yeux enfoncés¼. La formation et le soutien à la supervision étaient associés à de meilleures connaissances et compétences pour la diarrhée avec déshydratation, mais seulement à de meilleures connaissances pour la pneumonie. CONCLUSIONS: Les TPL sont cruciaux pour le système de santé indien, et des services de TPL de haute qualité sont nécessaires pour continuer à lutter contre les décès d'enfants de moins de cinq ans. L'écart entre les connaissances et les compétences des TPL mérite une attention immédiate. En particulier, nos résultats suggèrent que les formations axées sur les connaissances sont insuffisantes pour que les TPL convertissent les connaissances en compétences d'évaluation appropriées.