Exposure density and neighborhood disparities in COVID-19 infection risk.

Although there is increasing awareness of disparities in COVID-19 infection risk among vulnerable communities, the effect of behavioral interventions at the scale of individual neighborhoods has not been fully studied. We develop a method to quantify neighborhood activity behaviors at high spatial and temporal resolutions and test whether, and to what extent, behavioral responses to social-distancing policies vary with socioeconomic and demographic characteristics. We define exposure density ([Formula: see text]) as a measure of both the localized volume of activity in a defined area and the proportion of activity occurring in distinct land-use types. Using detailed neighborhood data for New York City, we quantify neighborhood exposure density using anonymized smartphone geolocation data over a 3-mo period covering more than 12 million unique devices and rasterize granular land-use information to contextualize observed activity. Next, we analyze disparities in community social distancing by estimating variations in neighborhood activity by land-use type before and after a mandated stay-at-home order. Finally, we evaluate the effects of localized demographic, socioeconomic, and built-environment density characteristics on infection rates and deaths in order to identify disparities in health outcomes related to exposure risk. Our findings demonstrate distinct behavioral patterns across neighborhoods after the stay-at-home order and that these variations in exposure density had a direct and measurable impact on the risk of infection. Notably, we find that an additional 10% reduction in exposure density city-wide could have saved between 1,849 and 4,068 lives during the study period, predominantly in lower-income and minority communities.

Modeling the cost-effectiveness of school-based supervised toothbrushing program in reducing the dental caries burden in India.

BACKGROUND: Supervised toothbrushing (STB) significantly reduces the incidence and progression of dental caries. School years present a favorable age for introducing such healthy habits for a lifetime. AIM: To estimate the cost-effectiveness of implementing a STB program in India in preventing dental caries incidence. DESIGN: An operational framework of a national STB program was devised. A mathematical model was then developed to evaluate this program's clinical effectiveness and economic impact in the Indian scenario. This study considered a hypothetical cohort of the Indian population aged from 6 to 75 years. Two groups were compared: no intervention and STB in government schools. The health outcomes assessed were a number of tooth caries incidences averted and quality-adjusted life years gained. RESULTS: The STB program in the government schools of India would prevent at least one tooth from developing caries in an individual's lifetime. Considering the current treatment-seeking behavior, the STB program saves INR 153 (US$ 1.95) per carious tooth incidence averted and INR 22 202 (US$ 283) per QALY gained. CONCLUSION: In India, the school-based STB program is expected to be a cost-effective strategy for reducing the dental caries burden and its associated treatment costs.

A penetratin-derived peptide reduces the membrane permeabilization and cell toxicity of α-synuclein oligomers.

Parkinson's disease is a neurodegenerative movement disorder associated with the intracellular aggregation of α-synuclein (α-syn). Cytotoxicity is mainly associated with the oligomeric species (αSOs) formed at early stages in α-syn aggregation. Consequently, there is an intense focus on the discovery of novel inhibitors such as peptides to inhibit oligomer formation and toxicity. Here, using peptide arrays, we identified nine peptides with high specificity and affinity for αSOs. Of these, peptides p194, p235, and p249 diverted α-syn aggregation from fibrils to amorphous aggregates with reduced ß-structures and increased random coil content. However, they did not reduce αSO cytotoxicity and permeabilization of large anionic unilamellar vesicles. In parallel, we identified a non-self-aggregating peptide (p216), derived from the cell-penetrating peptide penetratin, which showed 12-fold higher binding affinity to αSOs than to α-syn monomers (Kdapp 2.7 and 31.2 µM, respectively). p216 reduced αSOs-induced large anionic unilamellar vesicle membrane permeability at 10-1 to 10-3 mg/ml by almost 100%, was not toxic to SH-SY5Y cells, and reduced αSOs cytotoxicity by about 20%. We conclude that p216 is a promising starting point from which to develop peptides targeting toxic αSOs in Parkinson's disease.

Influence of periodontitis and diabetes on structure and cytokine content of platelet-rich fibrin.

BACKGROUND: Platelet-rich fibrin (PRF) is a second-generation platelet concentrate with multiple applications in wound healing and regeneration in both periodontitis and diabetes. However, the three dimensional (3-D) structure and cytokine content of PRF might be altered in patients suffering from either/both of the chronic inflammatory conditions, ultimately influencing the efficacy of PRF as a biomaterial for regenerative medicine. AIM: The aim of the present study was hence to evaluate the effect of both these chronic inflammatory diseases on the 3-D structure of PRF membrane. An attempt was also made to compare the growth factor content between the plasma and RBC ends of the prepared PRF gel. MATERIALS & METHODS: L-PRF was prepared for twenty participants, healthy (5), periodontitis (5), T2DM (5) and T2DM with periodontitis (5). Porosity and fiber diameter of PRF membranes was visualized under FE-SEM and measured using ImageJ Software. PDGF-BB and TGF-ß1 levels in PRF gel were assessed by ELISA. RESULTS: The average diameter of fibrin fibers under FE-SEM was 0.15 to 0.30 micrometers. Porosity was higher at the plasma end (p = 0.042). Red blood cell (RBC) end of the membrane had thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities. Healthy subjects had the least porous PRF compared to subjects with either/both of the chronic conditions. PDGF-BB levels were similar along all the four groups. TGF-ß1 levels were highest in healthy subjects. DISCUSSION: 3-D structure and growth factor content of PRF are influenced by a person's periodontal and/or diabetic status. The RBC end of the PRF membrane, as compared to the plasma end, has thinner fibers arranged in a comparatively more dense and compact structure with smaller porosities, and hence should be favored during periodontal regenerative procedures. CONCLUSION: Both periodontitis and diabetes have a significant influence on the 3-D structure and growth factor content of PRF produced.

"Does the Exploration of the Temporomandibular Joint Using a Deep Subfascial Technique Result in a Superior Operative Outcome?"

PURPOSE: The literature is replete with various approaches for the temporomandibular joint (TMJ), each with its own distinct advantages and disadvantages. None of these approaches, however, have been associated with superior operative outcomes. The purpose of this study was to measure the efficacy of three operative approaches to TMJ, namely superficial, subfascial, and deep subfascial approaches. The aim was to contrast selected intraoperative and postoperative outcomes among these surgical approaches. METHODS: This was a prospective randomized clinical trial of subjects presenting to outpatient department. The primary predictor variables were three dissection planes of TMJ: Group-I (superficial), Group-II (subfascial), and Group-III (deep subfascial). The primary outcome variables were quality of surgical field employing fromme scale, dissection time in minutes, amount of blood loss in milliliters, and facial nerve function (FNF) using House-Brackmann scale. The secondary outcome variables were postoperative pain using visual-analog scale and swelling in millimeters measured on 1st, 3rd, and 7th postoperative days and quality of life using facial clinimetric evaluation questionnaire at 6-month follow-up. Age, gender, side, diagnosis, and type of surgery were the covariates. The data were analyzed using descriptive, comparative, and regression analysis. A P value of less than .05 was considered statistically significant. RESULT: The study included thirty subjects (8 males and 22 females) with various TMJ disorders ranging in age from 8 years to 65 years (mean 27.83 ± 10.52). On evaluation of intraoperative parameters, subfascial approach had statistically significant superior quality of surgical field (Group-I: 1.90 ± 0.57; Group-II: 1.10 ± 0.32; Group-III: 1.40 ± 0.52; P value = .006), statistically significant shortest dissection time (Group-I: 18.30 ± 3.74 min; Group-II: 13.240 ± 1.96 min; Group-III: 16.20 ± 1.99 min; with P value = .03), and statistically significant lower amount of blood loss compared with other groups (Group-I: 92.40 ± 4.74 ml: Group-II: 82.30 ± 3.77 ml; Group-III: 84.60 ± 3.06 ml; P value<.001). On assessment of postoperative parameters, only FNF of temporal branch showed statistically significant difference from 24 hours till 3 months with better outcome in deep subfascial approach. Mean scores of FNF at 24 hours and 1-week (Group-I: 4.20 ± 2.39; Group-II: 2.40 ± 2.27; Group-III: 1.50 ± 1.58 P = .02) and 1-month and 3-month (Group-I: 2.70 ± 1.82; Group-II: 1.20 ± 0.63; Group-III: 1.00 ± 0.00 P = .04). CONCLUSIONS: The subfascial approach significantly improved intraoperative outcomes and deep subfascial approach was comparatively safe with fewer incidence of facial nerve injury.

Characterization of fetal exposure to multiple metals among an urban population: A case study of New York City.

INTRODUCTION: Metals and metalloids are ubiquitous and persistent in urban areas and are generally released into the environment as mixtures. OBJECTIVES: The purpose of this study was to establish baseline concentrations of selected elements in meconium samples among a large urban population in the US and understand the spatial variability in concentrations. The association of metal mixtures on birth weight was also assessed. METHODS: This cross-sectional study was conducted across five public hospitals located in New York City, NY (NYC) in four boroughs. We collected meconium sample from 116 infants during the first 24 h after delivery and quantified 11 metals using ICP-MS. Principal component analysis was used to determine metal mixtures and their association with birth weight. Spatial hot spots of each metal were calculated using the Getis-Ord (GI*). RESULTS: Essential elements were detected in all samples with Zn in the greatest abundance (median = 274.5 µg/g) and Mo in the least (median = 0.1845 µg/g). Pb was detected in all but two samples (median = 0.0222 µg/g), while Cd levels were detected in approximately half of the samples (median = 0.0019 µg/g). Co-located hot spots were detected for Cu, Zn, and Fe in southeast Brooklyn; Cd, Cr, and Ni in eastern Queens; and Al and Mo in south Queens. There was a significant inverse relationship between Pb concentrations (beta = -1935.7; p = 0.006) and the mixture of Cr, Cu, Mo, Zn (beta = -157.7; p = 0.045) and birth weight. CONCLUSIONS: Our findings indicate that meconium is an effective biomarker for measuring metal exposures among an urban population. We were able to quantify detectable levels of ten of the eleven metals measured in the study and characterize nutritionally necessary trace elements and metals derived from anthropogenic sources without biologic need in a cohort of NYC newborns. Further research needs to establish the change point from necessary to toxic, for the essential elements.

Herbal smoking products: a systematic content analysis and mapping of the e-retail market.

OBJECTIVE: To assess the online availability and e-marketing strategies of herbal smoking products (HSPs). METHODOLOGY: Google, Yahoo and Bing were searched using relevant keywords related to HSPs. The first 50 records were retrieved and duplicates were removed. Two trained and calibrated authors screened the records according to the eligibility criteria and extracted data from each selected retail-webpage as per the pre-tested data extraction form. RESULTS: Out of the initial 1044 records obtained, 73 retail webpages were finally included. Most of the webpages about HSPs hailed from India followed by the USA. The results showed 24 brands with about 189 flavour variants that are readily available online to all age groups including minors, with price per pack (20 sticks) of herbal cigarettes ranging from INR (₹) 51 to 1830 (median 588). There are no regulations regarding the sale and marketing of HSPs concerning age restrictions and display of health warnings. CONCLUSION: HSPs are readily available online at affordable prices and attractive variants for customers of all ages. The flavour appeal and the health benefit appeal is being used to target minors and young women. There is an urgent need for some regulations on the sale and e-marketing of such products that have an enormous potential to be used as a gateway to tobacco smoking.

Mother to Newborn Transmission of SARS-CoV-2 Infection: Evolution of Evidence in 1.5 Years of COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) pandemic caused significant mortality and morbidity in people of all age groups worldwide. Given the uncertainty regarding the mode of transmission and potential effects of COVID-19 on pregnant mothers and their newborns, guidelines for taking care of maternal-newborn dyads have evolved tremendously since the pandemic began. There has been an enormous influx of published materials regarding the outcomes of mothers and newborns. Still, multiple knowledge gaps regarding comprehensive information about risk to the mothers and newborns exist, which need to be addressed. Current evidence suggests that mothers with symptomatic COVID-19 infection are at increased risk of severe illness during pregnancy, with a higher need for respiratory support and premature deliveries. Neonates born to mothers with COVID-19 are at increased risk of needing intensive care; however, most newborns do well after birth. As new mutant variants arise, we need to be cautious while proactively understanding any new evolving patterns. All leading health authorities strongly recommend COVID-19 vaccination before or during pregnancy to reduce the risk of maternal morbidities and benefit from passing antibodies to newborns prenatally and via breastmilk. Additionally, there are racial, ethnic, and socioeconomic disparities in outcomes and vaccination coverage for pregnant women. This article summarizes the rapidly evolving evidence for the last 1.5 years and aims to help health care professionals care for mothers with COVID-19 and their newborns. KEY POINTS: · COVID-19 in pregnancy can cause perinatal morbidities.. · Breastfeeding and breast milk are safe for newborns.. · COVID-19 vaccination reduces the risk for morbidities..

Analysis of algal bloom intensification in mid-Ganga river, India, using satellite data and neural network techniques.

River Ganga is one of the most significant rivers in the country. This river is the adobe for numerous aquatic species and microorganisms. The color of the river suddenly changed to green due to the rise of algal bloom in the Varanasi and nearby regions of the river Ganga during May-June 2021. These algal blooms can be detrimental to the aquatic animals of the river. This study analyzes the occurrence and the possible reasons for the algal bloom generation in the river for the considered stretch. Several factors like nutrient accumulation in the river through agricultural run-off, warm river temperature, low flow condition of the river, thermal stratification, and less turbid river water can be considered as possible reasons for algal bloom development. In this work, the optical remote sensing-based Sentinel 2 datasets have been used for the duration of mid-May 2021 to mid-June 2021. These datasets have been processed in the Google Earth Engine (GEE) platform, and chlorophyll concentration has been calculated using different satellite-based indices or band ratios. The chlorophyll concentration measurements have quantified the algal bloom growth. These indices or band ratios have been analyzed using several artificial neural network (ANN) architectures like multilayer perceptron (MLP) and radial basis function (RBF) along with the in situ values. It has been found that chlorophyll concentration has been highest for the mid-June 2021 time period in the considered river stretch.

Dentinogenic Ghost Cell Tumor associated with Odontoma: A unique Histopathological Entity and its Surgical Management.

We report a rare case of dentinogenic ghost cell tumor (DGCT) associated with complex composite odontoma in a 17 years male affecting the posterior segment of the mandible. On radiographic examination, there was a well-defined multilocular radiolucency surrounding the radio opaque mass with respect to 44, 45 and 46. Histopathologically it showed ameloblastomatous proliferation with dentin like areas and ghost cells. It was associated with tooth like structures consisting of dentin, cementum and pulp like areas. DGCT with odontoma is extremely rare with only two cases being reported in literature till date. The management with its rare occurrence is discussed here.

Effectiveness-of Calcium Phosphate derivative agents on the prevention and remineralization of caries among children- A systematic review & meta-analysis of randomized controlled trials.

OBJECTIVES: Dental caries among children is a highly prevalent yet easily preventable oral health issue among children. Various calcium phosphate (CaP) derivatives are implicated to exhibit caries preventive potential; however, no study has summarized the anti-caries effectiveness of these agents. This systematic review and meta-analysis sought to assess the caries-preventive and tooth-remineralizing effect of various (CaP) derivative agents compared to no-intervention/placebo or Fluoride (F) use alone among children. MATERIALS AND METHODS: EMBASE, Ovid, PubMed, Scopus, Web of Science, Cochrane central register of controlled trials (CENTRAL), and grey literature were searched for relevant articles up to April 2021. Only English-language articles were included. Total 2636 articles were searched through different databases; out of the 2161 articles were screened after duplicate removal. 26 studies fulfilling the eligibility criteria were included in this systematic review. Methodological quality assessment and quantitative analysis were done using RevMan. GRADE was used to evaluate the certainty of evidence. RESULTS: A total of 26 trials fulfilling the eligibility criteria were included. The meta-analysis of 10 studies revealed that complete white spot lesions (WSLs) regression (RR=1.56; 95% CI, 1.27 to 1.91; P < .0001, I2=0%), post intervention active WSLs (RR=0.80; 95% CI, 0.70 to 0.90; P = .0004, I2=0%) and post intervention Salivary S. mutans count (RR= 0.69; 95% CI, 0.48 to 0.99; P = .47, I2=0%) significantly favored the CaP+F combined therapy as compared to F alone. No significant differences in the lesion area, Delta F, and DIAGNOdent values were observed between the 2 groups. Low certainty of the evidence was found in the present systematic review due to the high/unclear risk of bias, imprecision, and indirectness of included trials. CONCLUSIONS: Topical treatment using CaP+F group showed superior remineralization potential as well as the antibacterial effect on dental caries among children as compared to no intervention and/or placebo or F alone. Apart from CPP-ACP, other CaP derivatives like TCP and fTCP seem to have promising effects in remineralizing early lesions, however, very few trials exist on these potential agents. To provide definitive recommendations in this area, more clinical trials on caries preventive effectiveness of various CaP agents are warranted.

The yeast stress inducible Ssa Hsp70 reduces α-synuclein toxicity by promoting its degradation through autophagy.

The mechanism underlying the role of Hsp70s in toxicity associated with intracellular accumulation of toxic protein inclusions is under intense investigation. In current study, we examined the roles of all different isoforms of yeast cytosolic Ssa Hsp70 on α-synuclein mediated cellular toxicity. The study showed that yeast cells expressing stress-inducible Ssa3 or Ssa4 as sole Ssa Hsp70 isoforms, reduced α-synuclein toxicity better than those expressing a constitutive counterpart. The protective effect of stress-inducible Ssa Hsp70s was not α-syn specific, but more general to other inclusion forming proteins such as polyQ. We show that the protective effect is not by induction of a general stress response in Ssa3 cells rather by promoting α-synuclein degradation through autophagy. The present study revealed that effect of Hsp70s was isoform dependent, and that autophagy protects Ssa3 cells from the deleterious effects of toxic protein inclusions.

Effectiveness of a web-based learning module on oral health promotion for nursing and allied health professionals.

Background Nursing and allied health professionals are helping hands for healthcare and are important in the training cascade. We aimed to develop and validate the effectiveness of a web-based learning module on oral health promotion among nursing and allied health professionals. Methods We developed and validated an oral health module focused on prevention and promotion for a web-based intervention among nurses and allied health professionals. Pre- and post-test assessment was conducted to evaluate the effectiveness of the programme. Results Of a total of 347 participants, 170 (48.9%) had a good knowledge score in the pre-test, and after attending the oral health module their number increased to 267 (76.9%). The mean difference between the pre-test and post-test scores was statistically significant (p<0.005). Conclusions Training of nurses and allied health professionals on oral health through a web-based module showed improvement in oral health literacy.

Remineralization potential and caries preventive efficacy of CPP-ACP/Xylitol/Ozone/Bioactive glass and topical fluoride combined therapy versus fluoride mono-therapy - a systematic review and meta-analysis.

OBJECTIVE: To compare the remineralization potential and caries preventive efficacy of CPP-ACP/bioactive glass/xylitol/ozone and topical fluoride (TF) combined therapy versus TF mono-therapy. MATERIAL AND METHODS: Embase, PubMed, Scopus, Web of Science and Cochrane databases were searched. 4457 records were screened and 26 trials were included. Data from 16 trials was pooled using Review Manager 5.4. Level of significance was p < .05. The certainty of the evidence was evaluated using GRADE. RESULTS: Pooled analysis of two trials for white spot lesions (WSLs) regression (SMD -0.6, 95% CI: [-1.07 to -0.14], p = .01) and three trials for post-intervention DIAGNOdent values (SMD -1.24, 95% CI: [-1.96 to -0.52], p = .0007) significantly favoured CPP-ACP-TF combined therapy over TF mono-therapy. The sub-group analysis for caries increment (SMD -0.14, 95% CI: [-0.21 to -0.07], p < .0001) and the post intervention S mutans count (SMD -0.42, 95% CI: [-0.62 to -0.23], p < .0001) significantly favours 'xylitol-TF' and 'CPP-ACP-TF' combined therapy respectively. The high/unclear risk of bias, imprecision and indirectness of the included trials presented a low certainty of evidence. CONCLUSION: CPP-ACP-TF exhibits superiority over TF monotherapy in remineralizing existing lesions and demonstrates better antibacterial effect, whereas it is not more effective for preventing caries incidence. However, Xylitol exerts an added benefit over fluoride alone in preventing caries increment. The low-certainty evidence highlights the need for more good quality trials.

Adherence to the tobacco-free educational institution guidelines at schools of Raipur Rani, Haryana.

Tobacco-Free Educational Institution (ToFEI) guidelines are required to be followed by the schools. This cross-sectional study conducted in the year 2019 assessed the accordance with ToFEI guidelines among all the 84 schools of Raipur Rani educational block, Haryana. Investigators collected data from all the government (71) and private (13) schools during school working days. Tobacco sales within 100 yards of the school premises was covertly observed. None of the schools thoroughly complied with the tobacco-free school policy, though the compliance score for private schools (26.77 ± 19.15) was better than the government schools (13.65 ± 4.38). Only two private schools achieved the mandatory score of 50. All private schools and few government schools (42.3%) had successfully implemented the ban on tobacco sale within 100 yards of the school. None of the schools could achieve a ToFEI status in the present study. The policymakers and implementers should prioritize ToFEI agenda & support schools in achieving tobacco-free status.

Gastrointestinal Stomas and Fistulas: What is Lost and What to Do?

Abnormal connections between gastrointestinal tract (GIT) and skin are called enterocutaneous fistulas (ECFs). Presence of ECF is associated with significant morbidity and mortality. A stoma refers to a surgically created opening in the abdomen to divert feces or urine to the outside of the body, to compensate for partial or complete loss of bowel function. Gastrointestinal (GI) stomas and postoperative ECFs present a unique challenge to the intensivist due to development of malnutrition, dehydration, and sepsis leading to high morbidity and mortality. This review focuses on the basic concepts about the type of fistula and stomas, their indications and complications, and management. Principles of clinical management include replacement of fluid and electrolyte losses, control of sepsis along with reducing fistula output, prevention of malnutrition and psychological support, and skin care. How to cite this article: Pande RK, Gupta A. Gastrointestinal Stomas and Fistulas: What is Lost and What to Do? Indian J Crit Care Med 2020;24(Suppl 4):S175-S178.

A community-based pragmatic, controlled trial for preventing and reducing oral diseases among 1-6-year-old children visiting Anganwadi centers, under the Integrated Child Development Scheme, India.

BACKGROUND: Early childhood caries (ECC) has reached epidemic proportions affecting millions of children worldwide. Its prevention becomes imperative owing to the significant morbidity and financial implications involved with its treatment. The Integrated Child Development Scheme (ICDS), launched in India to provide mid-day meals, pre-school education and primary healthcare to children, can be utilised to counsel and deliver oral health education to mothers. The purpose of the study is to compare the effect of an oral health care package (OHCP) with usual care on the change in dental disease status among 1 to 3-year-old children at Anganwadi centres (AWC) in periurban areas of Chandigarh and rural areas of Cuttack, Orissa over a follow-up period of three years. METHODS: Two geographically distant ICDS blocks would be selected at each of the two study sites and would be randomly allocated to intervention and control group. Closely located AWCs under each of the selected blocks shall constitute the study setting. OHCP would be delivered to the mothers of the 1-6-year-old children enrolled in the AWCs of the experimental group whereas mothers under control group would receive usual care advice available at the AWCs. DISCUSSION: ECC prevention had conventionally focused upon testing effectiveness of programs targeting behaviour change among the caregivers and children, but surprisingly minimal efforts have been made to seek translation of these efforts into reduction of ECC at the community level. The present study has two components; testing effect of altering maternal and child behavioral aspects on ECC incidence through cohort follow up of 1-3-year-old children for three consecutive years and cross-sectional follow up of all available 1-6-year old children at the selected AWCs at regular intervals to look for change in prevalence of ECC at community level. In other regions of the world surveys of ECC prevalence before and after the intensive educational programs have shown a significant reduction in ECC prevalence. A similar decline can be anticipated through this program. TRIAL REGISTRATION: This trial has been prospectively registered at Clinical Trials Registry, India (CTRI/2019/02/017556, 08 February 2019).

Hsp90-Associated Immunophilin Homolog Cpr7 Is Required for the Mitotic Stability of [URE3] Prion in Saccharomyces cerevisiae.

The role of Hsp70 chaperones in yeast prion propagation is well established. Highly conserved Hsp90 chaperones participate in a number of cellular processes, such as client protein maturation, protein degradation, cellular signalling and apoptosis, but little is known about their role in propagation of infectious prion like aggregates. Here, we examine the influence of Hsp90 in the maintenance of yeast prion [URE3] which is a prion form of native protein Ure2, and reveal a previously unknown role of Hsp90 as an important regulator of [URE3] stability. We show that the C-terminal MEEVD pentapeptide motif, but not the client maturation activity of Hsp90, is essential for [URE3] prion stability. In testing deletions of various Hsp90 co-chaperones known to bind this motif, we find the immunophilin homolog Cpr7 is essential for [URE3] propagation. We show that Cpr7 interacts with Ure2 and enhances its fibrillation. The requirement of Cpr7 is specific for [URE3] as its deletion does not antagonize both strong and weak variant of another yeast prion [PSI+], suggesting a distinct role of the Hsp90 co-chaperone with different yeast prions. Our data show that, similar to the Hsp70 family, the Hsp90 chaperones also influence yeast prion maintenance, and that immunophilins could regulate protein multimerization independently of their activity as peptidyl-prolyl isomerases.

Report from a symposium on accelerating policy-driven action against excessive sugar consumption for the prevention of early childhood caries and noncommunicable diseases.

Dental diseases and other noncommunicable diseases (NCDs) share common risks. Omnipresent and easily available sugars are a contributing risk factor for overweight, obesity, and diabetes. In addition, sugar consumption is known to cause dental caries in early childhood (early childhood caries) and in adults. It has been noticed that the prevalence of NCDs is increasing each year, leading to 70% of deaths. A symposium of diverse academicians was convened to identify the gaps in evidence, policy, and advocacy for action on sugars, emphasizing on its detrimental effects on oral health. Existence of policies on sugars, experiences of other countries, feasibility in India, and the role of public health dentists, public, and stakeholders were discussed. Policy priorities in India and advocacy to strengthen action against inappropriate sugar intake could help address the growing burden of sugar-related NCDs. Recommendations to this end were put forth by the panel of experts.

High throughput screen identifies small molecule inhibitors specific for Mycobacterium tuberculosis phosphoserine phosphatase.

The emergence of drug-resistant strains of Mycobacterium tuberculosis makes identification and validation of newer drug targets a global priority. Phosphoserine phosphatase (PSP), a key essential metabolic enzyme involved in conversion of O-phospho-l-serine to l-serine, was characterized in this study. The M. tuberculosis genome harbors all enzymes involved in l-serine biosynthesis including two PSP homologs: Rv0505c (SerB1) and Rv3042c (SerB2). In the present study, we have biochemically characterized SerB2 enzyme and developed malachite green-based high throughput assay system to identify SerB2 inhibitors. We have identified 10 compounds that were structurally different from known PSP inhibitors, and few of these scaffolds were highly specific in their ability to inhibit SerB2 enzyme, were noncytotoxic against mammalian cell lines, and inhibited M. tuberculosis growth in vitro. Surface plasmon resonance experiments demonstrated the relative binding for these inhibitors. The two best hits identified in our screen, clorobiocin and rosaniline, were bactericidal in activity and killed intracellular bacteria in a dose-dependent manner. We have also identified amino acid residues critical for these SerB2-small molecule interactions. This is the first study where we validate that M. tuberculosis SerB2 is a druggable and suitable target to pursue for further high throughput assay system screening.