Filosofia come stile di vita. Conversazione con Luigi Vero Tarca

OBJECTIVE: To examine factors associated with chronic energy deficiency (CED) and anaemia in disadvantaged Indian adults who are mostly involved in subsistence farming. DESIGN: A cross-sectional study in which we collected information on socio-demographic factors, physical activity, anthropometry, blood haemoglobin concentration, and daily household food intake. These data were used to calculate body mass index (BMI), basal metabolic rate (BMR), daily energy expenditure, and energy and nutrient intake. Multivariable backward stepwise logistic regression was used to assess socioeconomic and lifestyle factors associated with CED (defined as BMI<18 kg/m²) and anaemia. SETTING: The study was conducted in 12 villages, in the Rishi Valley, Andhra Pradesh, India. SUBJECTS: Individuals aged 18 years and above, residing in the 12 villages, were eligible to participate. RESULTS: Data were available for 1178 individuals (45% male, median age 36 years (inter quartile range (IQR 27-50)). The prevalence of CED (38%) and anaemia (25%) was high. Farming was associated with CED in women (2.20, 95% CI: 1.39-3.49) and men (1.71, 95% CI: (1.06-2.74). Low income was also significantly associated with CED, while not completing high school was positively associated with anaemia. Median iron intake was high: 35.7 mg/day (IQR 26-46) in women and 43.4 mg/day (IQR 34-55) in men. CONCLUSIONS: Farming is an important risk factor associated with CED in this rural Indian population and low dietary iron is not the main cause of anaemia. Better farming practice may help to reduce CED in this population

Effectiveness of a scalable group-based education and monitoring program, delivered by health workers, to improve control of hypertension in rural India: A cluster randomised controlled trial

New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678)

An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages

Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis

Novel Role of Phosphorylation-Dependent Interaction between FtsZ and FipA in Mycobacterial Cell Division

The bacterial divisome is a multiprotein complex. Specific protein-protein interactions specify whether cell division occurs optimally, or whether division is arrested. Little is known about these protein-protein interactions and their regulation in mycobacteria. We have investigated the interrelationship between the products of the Mycobacterium tuberculosis gene cluster Rv0014c-Rv0019c, namely PknA (encoded by Rv0014c) and FtsZ-interacting protein A, FipA (encoded by Rv0019c) and the products of the division cell wall (dcw) cluster, namely FtsZ and FtsQ. M. smegmatis strains depleted in components of the two gene clusters have been complemented with orthologs of the respective genes of M. tuberculosis. Here we identify FipA as an interacting partner of FtsZ and FtsQ and establish that PknA-dependent phosphorylation of FipA on T77 and FtsZ on T343 is required for cell division under oxidative stress. A fipA knockout strain of M. smegmatis is less capable of withstanding oxidative stress than the wild type and showed elongation of cells due to a defect in septum formation. Localization of FtsQ, FtsZ and FipA at mid-cell was also compromised. Growth and survival defects under oxidative stress could be functionally complemented by fipA of M. tuberculosis but not its T77A mutant. Merodiploid strains of M. smegmatis expressing the FtsZ(T343A) showed inhibition of FtsZ-FipA interaction and Z ring formation under oxidative stress. Knockdown of FipA led to elongation of M. tuberculosis cells grown in macrophages and reduced intramacrophage growth. These data reveal a novel role of phosphorylation-dependent protein-protein interactions involving FipA, in the sustenance of mycobacterial cell division under oxidative stress

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Antioxidants l-carnitine and d-methionine modulate neuronal activity through GABAergic inhibition

Article on antioxidants L-carnitine and D-methionine modulate neuronal activity through GABAergic inhibition

Bioresource status in Karnataka

Energy is a vital component of any society playing a pivotal role in the development. Post oil crises shifted the focus of energy planners towards renewable resources and energy conservation. Biomass is one such renewable, which accounts for nearly 33% of a developing country’s energy needs. In India, it meets about 75% of the rural energy needs. In Karnataka, non-commercial energy sources like firewood, agricultural residues, charcoal and cow dung account for 53.2%. The energy released by the reaction of organic carbon (of bioresources) with oxygen is referred to as bioenergy. Bioresource availability is highly diversified and it depends on the region’s agroclimatic conditions. Inventorying of these resources is required for describing the quality, quantity, change, productivity, condition of bioresources and requirement in a given area. The present study assesses bioresource status across the agroclimatic zones of Karnataka, considering the bioenergy availability (from agriculture, horticulture, forests and plantations) and sector-wise energy demand (domestic, agriculture, industry, etc.). Bioresource availability is computed based on the compilation of data on the area and productivity of agriculture and horticulture crops, forests and plantations. Sector-wise energy demand is computed based on the National Sample Survey Organisation (NSSO study) data, primary survey data and from the literature. Using the data of bioresource availability and demand, bioresource status is computed for all the agroclimatic zones. The ratio of bioresource availability to demand gives the bioresource status. The ratio greater than one indicates bioresource surplus zones, while a ratio less than one indicates scarcity. The study reveals that the central dry zone (1.4), the hilly zone (3.79), the southern transition zone (3.12) and the coastal zone (3.40) are bioresource surplus zones, whereas the northeastern transition zone (0.48), northeastern dry zone (0.23), northern dry zone (0.58), eastern dry zone (0.39), southern dry zone (0.93) and northern transition zone (0.45) come under bioresource-deficient zones. Among the bioresource surplus zones, horticulture residues contribute significantly towards bioenergy in the central dry zone, southern transition zone and the coastal zone, while in the hilly zone the main contributor of bioenergy are agricultural residues. Amidst the bioresource-deficient zones, agriculture is the major contributor of bioenergy in the northeastern transition zone (52%), northern dry zone (59%), and northern transition zone. Based on the bioenergy status of the zones and land use pattern, feasible management and technical options have been discussed, which help in optimising the available bioenergy and in building a sustainable energy society. This study also explores various programmes that can be initiated and implemented like social, community and joint forest management involving public participation. Such schemes will lessen the burden on the existing resources and also help the rural masses to procure biomass on a sustained basis

Bioresource status in Karnataka

Energy is a vital component of any society playing a pivotal role in the development. Post oil crises shifted the focus of energy planners towards renewable resources and energy conservation. Biomass is one such renewable, which accounts for nearly 33% of a developing country's energy needs. In India, it meets about 75% of the rural energy needs. In Karnataka, non-commercial energy sources like firewood, agricultural residues, charcoal and cow dung account for 53.2%. The energy released by the reaction of organic carbon (of bioresources) with oxygen is referred to as bioenergy. Bioresource availability is highly diversified and it depends on the region's agroclimatic conditions. Inventorying of these resources is required for describing the quality, quantity, change, productivity, condition of bioresources and requirement in a given area. The present study assesses bioresource status across the agroclimatic zones of Karnataka, considering the bioenergy availability (from agriculture, horticulture, forests and plantations) and sector-wise energy demand (domestic, agriculture, industry, etc.). Bioresource availability is computed based on the compilation of data on the area and productivity of agriculture and horticulture crops, forests and plantations. Sector-wise energy demand is computed based on the National Sample Survey Organisation (NSSO study) data, primary survey data and from the literature. Using the data of bioresource availability and demand, bioresource status is computed for all the agroclimatic zones. The ratio of bioresource availability to demand gives the bioresource status. The ratio greater than one indicates bioresource surplus zones, while a ratio less than one indicates scarcity. The study reveals that the central dry zone (1.4), the hilly zone (3.79), the southern transition zone (3.12) and the coastal zone (3.40) are bioresource surplus zones, whereas the northeastern transition zone (0.48), northeastern dry zone (0.23), northern dry zone (0.58), eastern dry zone (0.39), southern dry zone (0.93) and northern transition zone (0.45) come under bioresource-deficient zones. Among the bioresource surplus zones, horticulture residues contribute significantly towards bioenergy in the central dry zone, southern transition zone and the coastal zone, while in the hilly zone the main contributor of bioenergy are agricultural residues. Amidst the bioresource-deficient zones, agriculture is the major contributor of bioenergy in the northeastern transition zone (52%), northern dry zone (59%), and northern transition zone. Based on the bioenergy status of the zones and land use pattern, feasible management and technical options have been discussed, which help in optimising the available bioenergy and in building a sustainable energy society. This study also explores various programmes that can be initiated and implemented like social, community and joint forest management involving public participation. Such schemes will lessen the burden on the existing resources and also help the rural masses to procure biomass on a sustained basis.Biomass Bio-energy Availability Demand

COMPARATIVE EVALUATION OF EFFICACY AND DURABILITY OF SELF-CURE AND LIGHT-CURE DESENSITIZING AGENTS IN THE TREATMENT OF DENTIN HYPERSENSITIVITY- AN IN-VIVO STUDY

&lt;p&gt;&lt;strong&gt;Objectives:&lt;/strong&gt;This in vivo study aimed to compare the efficacy and durability of three different varnishes/Desensitizing agents. Fluoride varnish, self-cure varnish, and light-cure varnish were used to treat dentin hypersensitivity by blocking dentinal tubules.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and Methods:&lt;/strong&gt; A total of 60 patients were randomly assigned into three groups Group A: received desensitizing fluoride varnish (ProfluoridVarnish, Voco), Group B: received self-cure varnish (Systemp desensitizer, IvoclarVivadent) and Group C: received light-cure varnish (Admira Protect, Voco). Assessment of air and tactile sensitivity was done based on visual analogue scale scores at baseline, immediately after treatment, and one-monthpost-treatment. One-way ANOVA was used to assess the level of significance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt;The results showed there was no statistically significant difference in the VAS scores for tactile and evaporative stimuli between the three groups immediately after treatment. Group C – Admira Protect showed lesser mean VAS scores for both the stimuli immediately and after 30 days of application which was statistically significant with post&nbsp;hoc&nbsp;correction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt;Allthree varnishes were effective in treating DH immediately after a single application. Profluorid Varnish showed lessefficacy when compared to resin varnishes at the end of one month. Clinical effectiveness was less at the end of one month for Systemp desensitizer, a self-cure varnish when compared to Admira Protect a light cure varnish.&lt;/p&gt;&lt;p&gt;&nbsp;&lt;/p&gt