The 18S rRNA Methyltransferase DIMT-1 Regulates Lifespan in the Germline Later in Life.

Ribosome heterogeneity has emerged as an important regulatory control feature for determining which proteins are synthesized, however, the influence of age on ribosome heterogeneity is not fully understood. Whether mRNA transcripts are selectively translated in young versus old cells and whether dysregulation of this process drives organismal aging is unknown. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation as organisms age. In a directed RNAi screen, we identified the 18S rRNA N6'-dimethyl adenosine (m6,2A) methyltransferase, dimt-1, as a regulator of C. elegans lifespan and stress resistance. Lifespan extension induced by dimt-1 deficiency required a functional germline and was dependent on the known regulator of protein translation, the Rag GTPase, raga-1, which links amino acid sensing to the mechanistic target of rapamycin complex (mTORC)1. Using an auxin-inducible degron tagged version of dimt-1, we demonstrate that DIMT-1 functions in the germline after mid-life to regulate lifespan. We further found that knock-down of dimt-1 leads to selective translation of transcripts important for stress resistance and lifespan regulation in the C. elegans germline in mid-life including the cytochrome P450 daf-9, which synthesizes a steroid that signals from the germline to the soma to regulate lifespan. We found that dimt-1 induced lifespan extension was dependent on the daf-9 signaling pathway. This finding reveals a new layer of proteome dysfunction, beyond protein synthesis and degradation, as an important regulator of aging. Our findings highlight a new role for ribosome heterogeneity, and specific rRNA modifications, in maintaining appropriate translation later in life to promote healthy aging.

DNA damage signals from somatic uterine tissue arrest oogenesis through activated DAF-16.

Germ line integrity is crucial for progeny fitness. Organisms deploy the DNA damage response (DDR) signaling to protect the germ line from genotoxic stress, facilitating the cell-cycle arrest of germ cells and DNA repair or their apoptosis. Cell-autonomous regulation of germ line quality in response to DNA damage is well studied; however, how quality is enforced cell non-autonomously on sensing somatic DNA damage is less known. Using Caenorhabditis elegans, we show that DDR disruption, only in the uterus, when insulin/IGF-1 signaling (IIS) is low, arrests oogenesis in the pachytene stage of meiosis I, in a FOXO/DAF-16 transcription factor-dependent manner. Without FOXO/DAF-16, germ cells of the IIS mutant escape the arrest to produce poor-quality oocytes, showing that the transcription factor imposes strict quality control during low IIS. Activated FOXO/DAF-16 senses DDR perturbations during low IIS to lower ERK/MPK-1 signaling below a threshold to promote germ line arrest. Altogether, we elucidate a new surveillance role for activated FOXO/DAF-16 that ensures optimal germ cell quality and progeny fitness in response to somatic DNA damage.

Nested U-Net for Segmentation of Red Lesions in Retinal Fundus Images and Sub-image Classification for Removal of False Positives.

Diabetic retinopathy is a pathological change of the retina that occurs for long-term diabetes. The patients become symptomatic in advanced stages of diabetic retinopathy resulting in severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy stages. There is a need of an automated screening tool for the early detection and treatment of patients with diabetic retinopathy. This paper focuses on the segmentation of red lesions using nested U-Net Zhou et al. (Deep Learning in Medical Image Analysis and Multimodal Learning for Clinical Decision Support, Springer, 2018) followed by removal of false positives based on the sub-image classification method. Different sizes of sub-images were studied for the reduction in false positives in the sub-image classification method. The network could capture semantic features and fine details due to dense convolutional blocks connected via skip connections in between down sampling and up sampling paths. False-negative candidates were very few and the sub-image classification network effectively reduced the falsely detected candidates. The proposed framework achieves a sensitivity of [Formula: see text], precision of [Formula: see text], and F1-Score of [Formula: see text] for the DIARETDB1 data set Kalviainen and Uusutalo (Medical Image Understanding and Analysis, Citeseer, 2007). It outperforms the state-of-the-art networks such as U-Net Ronneberger et al. (International Conference on Medical Image Computing and Computer-Assisted Intervention, Springer, 2015) and attention U-Net Oktay et al. (Attention u-net: Learning where to look for the pancreas, 2018).

lBest-HS algorithm based concurrent L1 adaptive control for non-Linear systems.

This paper proposes a new approach for designing stable hybrid L1 adaptive controller employing lbest topological model of harmony search (HS) algorithm. The proposed design approach guarantees desired stability and simultaneously provides satisfactory tracking performance for a class of non-linear systems. The design methodology for the controller utilizes the meta-heuristic global search feature of HS algorithm and the local search phenomenon of L1 adaptive control strategy in tandem. The paper also analytically describes the superiority of lbest topological model compared to the conventional HS algorithm in terms of convergence phenomenon, when hybridized with L1 adaptive control. The proposed hybrid control methodology has been implemented for benchmark simulation case studies and real-time experimentation to demonstrate its usefulness.

Dietary restriction improves proteostasis and increases life span through endoplasmic reticulum hormesis.

Unfolded protein response (UPR) of the endoplasmic reticulum (UPRER) helps maintain proteostasis in the cell. The ability to mount an effective UPRER to external stress (iUPRER) decreases with age and is linked to the pathophysiology of multiple age-related disorders. Here, we show that a transient pharmacological ER stress, imposed early in development on Caenorhabditis elegans, enhances proteostasis, prevents iUPRER decline with age, and increases adult life span. Importantly, dietary restriction (DR), that has a conserved positive effect on life span, employs this mechanism of ER hormesis for longevity assurance. We found that only the IRE-1-XBP-1 branch of UPRER is required for the longevity effects, resulting in increased ER-associated degradation (ERAD) gene expression and degradation of ER resident proteins during DR. Further, both ER hormesis and DR protect against polyglutamine aggregation in an IRE-1-dependent manner. We show that the DR-specific FOXA transcription factor PHA-4 transcriptionally regulates the genes required for ER homeostasis and is required for ER preconditioning-induced life span extension. Finally, we show that ER hormesis improves proteostasis and viability in a mammalian cellular model of neurodegenerative disease. Together, our study identifies a mechanism by which DR offers its benefits and opens the possibility of using ER-targeted pharmacological interventions to mimic the prolongevity effects of DR.

Magnitude of Mental Morbidity and Its Correlates with Special Reference to Household Food Insecurity among Adult Slum Dwellers of Bankura, India: A Cross-Sectional Survey.

BACKGROUND: Mental disorders cause considerable morbidity and disability, and there is ample evidence that mental disorders are positively associated with household food insecurity. METHODS: A cross-sectional survey was conducted for a period of 2 months at Bakultala slum of Bankura town involving 152 people of ≥18 and ≤60 years of age selected using simple random sampling technique to estimate the prevalence of mental disorders and to find out its correlates. Information pertaining to socio-demographics and household food security (HHFS) and " potential psychiatric case" were collected through a house to house interview of the head of the household, using predesigned questionnaire, Bengali version of self-reporting questionnaire, and 6-item household food security scale (HFSS). RESULTS: In total, 45% of the study participants belonged to food unsecured households. Overall, 21% of the respondents were identified as "potential psychiatric case," which was found to be associated with higher age, illiteracy, divorcee female, and people living in households without food security. CONCLUSION: Study results reflecting high prevalence (21%) of "potential psychiatric case" with various correlates such as age, sex, education, marital status, and HHFS among the slum dweller of Bankura town may be helpful in formulating policies for combating mental health morbidities.

Road Traffic Injuries: A Study on Severity and Outcome among Inpatients of a Tertiary Care Level Hospital of West Bengal, India.

BACKGROUND: Road traffic injuries (RTIs) are a complex phenomenon caused by nonlinear combination and interaction of man, vehicles, road, and environment. AIM: This study aims to find out the outcome and severity of RTI in a district of West Bengal, India. SETTINGS AND DESIGN: A cross-sectional study was conducted among inpatients of Departments of Surgery and Orthopedics of Bankura Sammilani Medical College and Hospital, West Bengal, India. MATERIALS AND METHODS: The study was conducted for 1 year interviewing 295 RTI selected through scheduled sampling. Information pertaining to demographic and correlates of RTI was collected by face to face and over telephone using semi-structured questionnaire. Nine-item Simplified Injury Severity Scale (SISS) was used to assess injury severity. Internal consistency of SISS scale was showed by Cronbach's alpha and association with the correlates was done by Mann-Whitney U-test. STATISTICAL ANALYSIS USED: With SPSS version 22.0, binary logistic regression, and Mann-Whitney U-test. RESULTS AND CONCLUSION: Fatal outcome in terms of death and permanent disability was 34.24% and they had higher marginally significant (P = 0.06), SISS score (45.17 ± 12.59). Participants with absence of protective devices, presence of comorbidities, drunkenness, with accidents over national highways, in-between 6 am and 6 pm, mechanized two-wheelers, and nonreceipt of first aid were found to have significantly high scores compared to their counterpart. SISS, as a proxy measure of severity assessment, could throw a light on it and awareness generation and legislative stringency might be need of the hour for the country.

Correlation among perceived stress, emotional intelligence, and burnout of resident doctors in a medical college of West Bengal: A mediation analysis.

BACKGROUND: Perceived stress and burnout are by-products of powerless responsibility imposed on resident doctors. Emotional intelligence (EI) works as an adapting and coping tool. OBJECTIVE: The objective of this study is to find out the role of work-related perceived stress on burnout and influence of EI on it. METHODS:: A descriptive cross-sectional study was conducted from February to April 2016 among 63 resident doctors of different departments of Bankura Sammilani Medical College and Hospital. Data were collected through a self-administered questionnaire for background characteristics and work-related variables. Cohen perceived stress scale, Trait EI, and Shirom-Melamed burnout questionnaire were applied for measuring perceived stress, EI, and burnout, respectively. Statistical analysis was done with of SPSS version 22.0, and for mediation analysis, Andrew F. Hyne's SPSS macro was adopted. Nonparametric bootstrapping was done assuming small sample. RESULTS: Out of complete responses, 67%, 22.9%, and 9.8% were from clinical, paraclinical, and preclinical specialties, respectively. Burnout had a significant positive correlation with perceived stress and in negative correlation with EI-well-being and positive correlation with EI-self-control and sociability. Physical fatigue factor of burnout had a significant positive correlation with EI-emotionality. Perceived stress had a negative correlation with EI-well-being. On mediation analysis, assuming EI as a mediator, total, direct, and indirect effects of perceived stress on burnout were significant (<0.05). Mediation was proved to act with percent mediation of 0.07. CONCLUSION: There was definite mitigating effect of EI on burnout by perceived stress among resident doctors. This necessitates more attention by decision-makers toward this burning problem for the sake of care of caregivers.

Status of early childhood education under integrated child development services scheme in Bankura Municipality, West Bengal.

BACKGROUND: Early childhood education (ECE) is an important service provided by Integrated Child Development Services (ICDS). It is largely responsible for developing school readiness in children. OBJECTIVE: The objective of this study is to assess ECE component of ICDS services through measurement of school readiness and find out other correlates. METHODS: A cross-sectional evaluation study was carried out among Anganwadi centers (AWCs) under Bankura Municipality, West Bengal, India from July to November 2015. AWCs were selected by 30 cluster sampling. From each selected center Anganwadi worker (AWW), 7 randomly selected children of 5 years of age and their caregivers were included in the study. Data were collected by assessment of children, interview of AWWs and caregivers of children, observation of ECE activity and record review using ECE Program Evaluation Package developed by World Bank and predesigned schedule. Mean, standard deviation, proportions were estimated for description and correlation, unpaired t-test, analysis of one-way variance, multivariable linear regression were performed to find out correlates of school readiness using SPSS 22.0 version. RESULTS: Average duration of ECE activity was 66.0 min/day which was far less than the norm. Overall average score of school readiness of 210 children was 14.0 out of 40. Inadequate physical facility, poor classroom performance acted as deterrents for school readiness. Help in the study at home was revealed to be a determinant of school readiness. CONCLUSION: For the preparation of formal schooling of children most important needs of the hour are physical facility of AWCs, supportive supervision of AWWs, and creation of congenial environment at home.

Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis.

PURPOSE: Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. METHODS: Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. RESULTS: EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. CONCLUSIONS: Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

Is the coverage of mass-drug-administration adequate for elimination of Bancroftian filariasis? An experience from West Bengal, India.

BACKGROUND: Bancroftian filariasis is the second most common mosquito-borne disease in India. Government of India adopted mass-drug-administration (MDA) since 2004 for its elimination by 2015 AD. OBJECTIVE: The aim was to assess the coverage, compliance, factors-related to noncompliance to MDA. MATERIALS AND METHODS: A cross-sectional survey of 1 week was conducted within 2 weeks after completion of MDA for 2012 in three villages and two municipal wards of North 24 Parganas district of West Bengal, India selected as clusters by multistage random sampling. Information was collected via interview of inhabitants of the clusters selected by systematic random sampling and drug administrators of the selected clusters along with verifying left over medicines, if any. RESULTS: Both appropriate medicine distribution (83.4%) and 61.28% of people who received drug reported consumption and effective consumption rate (48.01%) fell short of the target. The lowest consumption (38.15%) was noted in one of the rural cluster (villages), followed by municipal wards (43.14%). Consumption was significantly higher among rural residents and Hindu community. Fear of the adverse reaction was the commonest (63.02%) cause of noncompliance. Contrary to the requirement, almost all consumptions were unsupervised by drug administrators. Only 10.71% of the respondents reportedly were paid house to house campaign of forthcoming MDA. About 64% participants had heard about filariasis out of which 71% & 47% mentioned swelling of legs as symptoms and mosquito bite as mode of spread, respectively. About one-third opined mosquito control and MDA each as means of prevention. Approximately, 60% participants had heard about MDA. Information education and communication related to MDA program was conspicuously inadequate in the last round. CONCLUSION: Mass mobilization as in intensive pulse polio immunization with effective monitoring and supervision is the need of the hour for universal coverage of MDA with supervised on the spot consumption of tablets.

A tertiary level hospital-based study on frequency of changing presbyopic glasses in primary open angle glaucoma patients.

A tertiary level hospital-based case control study on frequency of changing presbyopic glasses among primary open angle glaucoma cases was carried out jointly by the departments of community medicine and ophthalmology from 1st July to 31st December, 2008. Each of the case and control groups included 31 persons. Odd's ratio of 4.55 (95% CI = 1.37-15.68) using epi-info version 3.2 showed that among primary open angle glaucoma cases the time of changing spectacles at < or = 2 years was 4.55 times more than that among control group; Pearson's Chi-square test (chi2 = 7.94, df = 1, p = 0.00) was statistically significant; Z-test for proportion = 2.56, p=0.01. So changing spectacles at < or = 2 years among patients would help the paramedical workers/paramedical ophthalmic assistants in the community to refer the patients earlier to ophthalmologists for further investigation and management.

Determination of the orientational order parameter of the homologous series of 4-cyanophenyl 4-alkylbenzoate (n.CN) by different methods.

The orientational order parameters of a homologous series of 4-cyanophenyl 4-alkylbenzoates have been determined at different temperatures from (13)C-NMR, x-ray diffraction, optical birefringence, high resolution density and diamagnetic susceptibility anisotropy measurements. To determine the temperature dependence of the orientational order parameter from the (13)C chemical shift values, the two-dimensional polarization inversion spin exchange at the magic angle (PISEMA) method was also used for the measurement of (13)C-(1)H dipolar couplings at different sites in the oriented phase. The nematic order parameters determined from each of these methods have been compared. Apart from a slight shift in their values their trends with temperature are very similar. The differences among the results obtained by these five different methods have been discussed. From the high resolution density data, the values of the critical exponents near the T(N-I) transition are found to lie between the Ising model and tricritical behaviour.

Detection of methicillin resistance in Staphylococcus aureus by polymerase chain reaction and conventional methods: a comparative study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen worldwide, which has emerged over the past 30 years as a leading cause of both nosocomial and community-acquired infections. Accurate and rapid identification of MRSA in clinical specimens is essential for timely decision on effective antimicrobial chemotherapy. AIM: The present study was conducted to compare two conventional phenotypic methods, oxacillin disk diffusion (ODD) method and mannitol salt agar (MSA) with oxacillin, with polymerase chain reaction (PCR) for mecA gene (as standard). MATERIALS AND METHODS: A total of 165 consecutive clinical isolates of S. aureus received at the Department of Microbiology in our tertiary care teaching hospital were included in the study. All the isolates were subjected to ODD (1 µg) method, culture in MSA with oxacillin, and PCR for mecA gene. RESULTS: The sensitivity and specificity of ODD test were found to be 93.5% (86.4-97.3%) and 83.5% (79.2-85.8%), respectively, and that of MSA with oxacillin were found to be 87.1% (79.5-92.3%) and 89.3% (84.8-92.5%), respectively. The time taken for diagnosing MRSA by conventional methods is 48-72 h, which is more as compared to PCR which takes 18-24 h. CONCLUSION: This study recommends advocating PCR for mecA gene on a regular basis for detecting methicillin resistance in S. aureus isolates isolated from sterile body fluids or from special units such as intensive care units.