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Small non-coding RNAs (sRNAs) regulate the synthesis of virulence factors and other pathogenic traits, which enables the bacteria to survive and proliferate after host infection. While high-throughput sequencing data have proved useful in identifying sRNAs from the intergenic regions (IGRs) of the genome, it remains a challenge to present a complete genome-wide map of the expression of the sRNAs. Moreover, existing methodologies necessitate multiple dependencies for executing their algorithm and also lack a targeted approach for the de novo sRNA identification. We developed an Isolation Forest algorithm-based method and the tool Prediction Of sRNAs using Isolation Forest for the de novo identification of sRNAs from available bacterial sRNA-seq data ( http://posif.ibab.ac.in/ ). Using this framework, we predicted 1120 sRNAs and 46 small proteins in Mycobacterium tuberculosis . Besides, we highlight the context-dependent expression of novel sRNAs, their probable synthesis, and their potential relevance in stress response mechanisms manifested by M. tuberculosis.

Bioinformatic studies on small proteins are under-represented due to difficulties in annotation posed by their small size. However, recent discoveries emphasize the functional significance of small proteins in cellular processes including cell signaling, metabolism, and adaptation to stress. In this study, we utilized a Random Forest classifier trained on sequence features, RNA-Seq, and Ribo-Seq data to uncover small proteins (smORFs) in M. tuberculosis. Independent predictions for the exponential and starvation conditions resulted in 695 potential smORFs. We examined the functional implications of these smORFs using homology searches, LC-MS/MS, and ChIP-seq data, testing their expression in diverse growth conditions, and identifying protein domains. We provide evidence that some of these smORFs could be part of operons, or exist as upstream ORFs. This expanded data resource for the proteins of M. tuberculosis would aid in fine-tuning the existing protein and gene regulatory networks, thereby improving system-wide studies. The primary goal of this study was to uncover and characterize smORFs in M. tuberculosis through bioinformatic analysis, shedding light on their functional roles and genomic organization. Further investigation of these potential smORFs would provide valuable insights into the genome organization and functional diversity of the M. tuberculosis proteome.

Growth and wood traits of Leucaena leucocephala subsp. glabrata were compared with India's most widely grown pulpwood, Eucalyptus. Three Leucaena seedlots and sixty-four Leucaena clones selected in plantations established from two Indian land races and a Hawaiian seed source were tested together with five commercial E. camaldulensis clones at two contrasting sites in southern India. At the wetter, irrigated site, the three sources of Leucaena clones had significantly greater 4-year height and similar mean stem diameter to the Eucalyptus clones, while the Leucaena seedlots were slower-growing. At the semi-arid, rainfed site, Eucalyptus grew faster and had better survival than the three sources of Leucaena clones, which again were similar in their performance and superior to the Leucaena seedlots. Basic densities, determined from breast-height wood cores, of 4-year-old Leucaena and Eucalyptus were quite similar (568 and 534 kg m-3 respectively) at the irrigated site, but at the rainfed site Eucalyptus wood density was higher (590 kg m-3), while that of Leucaena was lower (508 kg m-3). The kraft pulp yield (KPY) of Leucaena clones was about 1.5 % higher than Eucalyptus at both sites; KPYs of both species were 1.8 % lower at the rainfed than the irrigated site. Leucaena fibres were 31 % and 39 % longer and 65 % and 58 % wider than Eucalyptus, at the irrigated and rainfed sites respectively, and had lower cell wall proportions. Differences among Leucaena clones were significant for growth traits and for most wood and fibre traits, indicating the potential for selecting fast-growing Leucaena clones with improved wood properties. Clonal Leucaena plantations can serve as a productive and complementary pulpwood crop to Eucalyptus in southern India, increasing the yield and strength of blended pulps.

Subclinical infection of laboratory animals with one or more of several pathogens affects the results of experiments on animals. Monitoring the health of laboratory animals encompasses routine surveillance for pathogens, including several viruses. This study aimed to explore the development of an alternative assay to the existing ones for detecting infection of mice and rats with the parvoviruses minute virus of mice (MVM) and Kilham rat virus (KRV), respectively. Full-length VP2 and NS1 proteins of these parvoviruses, besides fragments containing multiple predicted epitopes stitched together, were studied for serological detection. The optimal dilution of full-length proteins and antigenic regions containing predicted epitopes for coating, test sera, and conjugate was determined using a checkerboard titration at each step. The assays were evaluated vis-à-vis commercially available ELISA kits. The results showed that an engineered fusion of fragments containing multiple predicted MVM VP2 and NS1 epitopes was better than either of the full-length proteins for detecting antibodies in 90% of the tested sera samples. For KRV ELISA, full-length VP2 was better compared to other individual recombinant protein fragments or combinations thereof for the detection of antibodies in sera. This report is the first description of an ELISA for KRV and an improved assay for MVM. Importantly, our assays could be exploited with small volumes of sera. The results also demonstrate the utility of immunoinformatics-driven polypeptide engineering in the development of diagnostic assays and the potential to develop better tests for monitoring the health status of laboratory animals.

In recent years, conductive polymer nanocomposites have gained significant attention due to their promising thermoresistive and Joule heating properties across a range of versatile applications, such as heating elements, smart materials, and thermistors. This paper presents an investigation of semi-crystalline polyvinylidene fluoride (PVDF) nanocomposites with 6 wt.% carbon-based nanofillers, namely graphene nanoplatelets (GNPs), multi-walled carbon nanotubes (MWCNTs), and a combination of GNPs and MWCNTs (hybrid). The influence of the mono- and hybrid fillers on the crystalline structure was analyzed by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). It was found that the nanocomposites had increased amorphous fraction compared to the neat PVDF. Furthermore, nanocomposites enhanced the β phase of the PVDF by up to 12% mainly due to the presence of MWCNTs. The resistive properties of the nanocompositions were weakly affected by the temperature in the analyzed temperature range of 25–100 °C; nevertheless, the hybrid filler composites were proven to be more sensitive than the monofiller ones. The Joule heating effect was observed when 8 and 10 V were applied, and the compositions reached a self-regulating effect at around 100–150 s. In general, the inclusion in PVDF of nanofillers such as GNPs and MWCNTs, and especially their hybrid combinations, may be successfully used for tuning the self-regulated Joule heating properties of the nanocomposites.

Aim: To evaluate and compare the apical depth of penetration and postoperative pain associated with the use of 9% 1-Hydroxyethylidene-1, 1-Bisphosphonate (HEBP) along with 3% sodium hypochlorite (NaOCl) as continuous chelation and standard irrigation protocol in endodontic treatment of adult permanent nonvital teeth. Methods: In this parallel arm double-blind single-center randomized controlled trial, standard irrigation protocol was compared to continuous chelation protocol (HEBP/NaOCl combination) with respect to the apical depth of penetration of irrigant and the postoperative pain. Forty-six patients aged between 18 and 45 years presenting with nonvital teeth requiring root canal treatment were randomly divided into two groups (n = 23) based on irrigation regime. After the final irrigation protocol, the apical depth of penetration of the irrigant was evaluated using a radiovisiography and radiopaque dye. Postoperative pain levels were evaluated at 6 h and 24 h after treatment using the numerical rating scale. Results: The results revealed that there was no statistically significant difference between the two groups in terms of the apical depth of penetration of the irrigant. While, with respect to postoperative pain, a statistically significant difference was found between the two groups at 24 h, with lower pain values observed in the continuous chelation group. Conclusion: The use of soft chelating agents like HEBP in continuous chelation has the apical depth of penetration comparable to that of ethylenediaminetetraacetic acid (EDTA) in standard irrigation protocol with lower postoperative pain at 24 h. Therefore, HEBP with NaOCl in continuous chelation can be seen as a viable, economical, and less technique-sensitive alternative to the use of EDTA for an effective three-dimensional disinfection of the root canal system up to the apical third of the root, which can be easily incorporated into daily clinical practice.

Aim: Different approaches are used to determine the working length of the root canal. The current and most widely researched are the electronic apex locators (EALs). Since the early apex locators were developed in 1942, several generations had their qualities and shortcomings developed. Thus, a comparative evaluation of the accuracy of different generations of EALs in determining the correct working length: Systemic review and meta-analysis to analyze individual studies quantitively and draw conclusions on the best generation of apex locator currently used. Materials and Methods: A comprehensive search was conducted on different electronic databases and by manual search. Studies comparing third and fifth generations with fourth-generation apex locators were subject to strict inclusion criteria followed by data extraction and meta-analysis. Results: Following the meta-analysis, the accuracy is fifth>fourth>third generation of apex locators. Conclusion: Analysis of individual studies quantitatively will give a better understanding of which devices to use to accurately determine the working length.

Abstract Background Bovine mastitis accounts for significant economic losses to the dairy industry worldwide. Staphylococcus aureus is the most common causative agent of bovine mastitis. Investigating the prevalence of virulence factors and antimicrobial resistance would provide insight into the molecular epidemiology of mastitis-associated S. aureus strains. The present study is focused on the whole genome sequencing and comparative genomic analysis of 41 mastitis-associated S. aureus strains isolated from India. Results The results elucidate explicit knowledge of 15 diverse sequence types (STs) and five clonal complexes (CCs). The clonal complexes CC8 and CC97 were found to be the predominant genotypes comprising 21 and 10 isolates, respectively. The mean genome size was 2.7 Mbp with a 32.7% average GC content. The pan-genome of the Indian strains of mastitis-associated S. aureus is almost closed. The genome-wide SNP-based phylogenetic analysis differentiated 41 strains into six major clades. Sixteen different spa types were identified, and eight isolates were untypeable. The cgMLST analysis of all S. aureus genome sequences reported from India revealed that S. aureus strain MUF256, isolated from wound fluids of a diabetic patient, was the common ancestor. Further, we observed that all the Indian mastitis-associated S. aureus isolates belonging to the CC97 are mastitis-associated. We identified 17 different antimicrobial resistance (AMR) genes among these isolates, and all the isolates used in this study were susceptible to methicillin. We also identified 108 virulence-associated genes and discuss their associations with different genotypes. Conclusion This is the first study presenting a comprehensive whole genome analysis of bovine mastitis-associated S. aureus isolates from India. Comparative genomic analysis revealed the genome diversity, major genotypes, antimicrobial resistome, and virulome of clinical and subclinical mastitis-associated S. aureus strains.

The tender shoots of Caesalpinia mimosoides Lam. are used ethnomedically by the traditional healers of Uttara Kannada district, Karnataka (India) for the treatment of wounds. The current study was aimed at exploring phenol-enriched fraction (PEF) of crude ethanol extract of tender shoots to isolate and characterize the most active bio-constituent through bioassay-guided fractionation procedure. The successive fractionation and sub-fractionation of PEF, followed by in vitro scratch wound, antimicrobial, and antioxidant activities, yielded a highly active natural antioxidant compound ethyl gallate (EG). In vitro wound healing potentiality of EG was evidenced by a significantly higher percentage of cell migration in L929 fibroblast cells (97.98 ± 0.46% at 3.81 μg/ml concentration) compared to a positive control group (98.44 ± 0.36%) at the 48th hour of incubation. A significantly higher rate of wound contraction (98.72 ± 0.41%), an elevated tensile strength of the incised wound (1,154.60 ± 1.42 g/mm2), and increased quantity of connective tissue elements were observed in the granulation tissues of the 1% EG ointment treated animal group on the 15th post-wounding day. The accelerated wound healing activity of 1% EG was also exhibited by histopathological examinations through Hematoxylin and Eosin, Masson’s trichome, and Toluidine blue-stained sections. Significant up-regulation of enzymatic and non-enzymatic antioxidant contents (reduced glutathione, superoxide dismutase, and catalase) and down-regulation of oxidative stress marker (lipid peroxidation) clearly indicates the effective granular antioxidant activity of 1% EG in preventing oxidative damage to the skin tissues. Further, in vitro antimicrobial and antioxidant activities of EG supports the positive correlation with its enhanced wound-healing activity. Moreover, molecular docking and dynamics for 100 ns revealed the stable binding of EG with cyclooxygenase-2 (−6.2 kcal/mol) and matrix metalloproteinase-9 (−4.6 kcal/mol) and unstable binding with tumor necrosis factor-α (−7.2 kcal/mol), suggesting the potential applicability of EG in inflammation and wound treatment.

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

Abstract In this paper, we show how we developed a visualisation tool to challenge perceived notions about biosecurity on poultry farms. Veterinarians and veterinary public health professionals tend to present biosecurity measures as a universal and cost-effective solution for preventing and controlling diseases on farms. However, we illustrate how biosecurity is an ill-defined term, making it difficult to talk about or apply in practice. As a result, we demonstrate how we moved away from using the term biosecurity in our research by designing a visualisation tool. The tool was to allow us to open up dialogue around disease prevention and control, and make tangible the tacit situated practices of stakeholders working along the poultry supply chain. Our findings show that for those working along the poultry supply chain, the term biosecurity was either consistently open to interpretation, or too rigid to reflect or allow for local variations. We conclude by highlighting how our visualisation tool offers insights into why researchers must move beyond using biosecurity as a term, and instead envisage, design, and develop local solutions to prevent and control diseases on poultry farms.

Background Bovine ephemeral fever (BEF) is a re-emerging disease caused by bovine ephemeral fever virus (BEFV). Although it poses a huge economic threat to the livestock sector, complete viral genome information from any South Asian country, including India, lacks. Aim Genome characterization of the first Indian BEFV isolate and to evaluate its genetic diversity by characterizing genomic mutations and their associated protein dynamics. Materials and Methods Of the nineteen positive blood samples collected from BEF symptomatic animals during the 2018-19 outbreaks in India, one random sample was used to amplify the entire viral genome by RT-PCR. Utilizing Sanger sequencing and NGS technology, a complete genome was determined. Genome characterization, genetic diversity and phylogenetic analyses were explored by comparing the results with available global isolates. Additionally, unique genomic mutations within the Indian isolate were investigated, followed by in-silico assessment of non-synonymous (NS) mutations impacts on corresponding proteins’ secondary structure, solvent accessibility and dynamics. Results The complete genome of Indian BEFV has 14,903 nucleotides with 33% GC with considerable genetic diversity. Its sequence comparison and phylogenetic analysis revealed a close relatedness to the Middle Eastern lineage. Genome-wide scanning elucidated 30 unique mutations, including 10 NS mutations in the P, L and GNS proteins. The mutational impact evaluation confirmed alterations in protein structure and dynamics, with minimal effect on solvent accessibility. Additionally, alteration in the interatomic interactions was compared against the wild type. Conclusion These findings extend our understanding of the BEFV epidemiological and pathogenic potential, aiding in developing better therapeutic and preventive interventions.

Abstract An increased surge of -omics data for the diseases such as cancer allows for deriving insights into the affiliated protein interactions. We used bipartite network principles to build protein functional associations of the differentially regulated genes in 18 cancer types. This approach allowed us to combine expression data to functional associations in many cancers simultaneously. Further, graph centrality measures suggested the importance of upregulated genes such as BIRC5, UBE2C, BUB1B, KIF20A and PTH1R in cancer. Pathway analysis of the high centrality network nodes suggested the importance of the upregulation of cell cycle and replication associated proteins in cancer. Some of the downregulated high centrality proteins include actins, myosins and ATPase subunits. Among the transcription factors, mini-chromosome maintenance proteins (MCMs) and E2F family proteins appeared prominently in regulating many differentially regulated genes. The projected unipartite networks of the up and downregulated genes were comprised of 37,411 and 41,756 interactions, respectively. The conclusions obtained by collating these interactions revealed pan-cancer as well as subtype specific protein complexes and clusters. Therefore, we demonstrate that incorporating expression data from multiple cancers into bipartite graphs validates existing cancer associated mechanisms as well as directs to novel interactions and pathways.

Caesalpinia mimosoides Lam. is one of the important medicinal plants used by the traditional healers of Uttara Kannada district, Karnataka (India) for treating wounds. In our previous study ethanol extract of the plant was evaluated for its wound healing activity. In continuation, the present study was aimed to evaluate the phenol enriched fraction (PEF) of ethanol extract for wound healing activity along with its antioxidant, anti-inflammatory and antimicrobial properties. The potent wound healing activity of PEF was evidenced by observation of increased rate of cell migration in L929, 3T3L1 and L6 cells (92.59 ± 1.53%, 98.42 ± 0.82% and 96.63 ± 0.61% respectively) at 7.81 μg/ml doses in assays carried out in vitro. Significantly enhanced rate of wound contraction (97.92 ± 0.41%), tensile strength (973.67 ± 4.43 g/mm2), hydroxyproline (31.31 ± 0.64 mg/g) and hexosamine (8.30 ± 0.47 mg/g) contents were observed on 15th post wounding day in 5% PEF treated animals. The enzymatic and non-enzymatic cellular antioxidants (superoxide dismutase, catalase and reduced glutathione) were upregulated (15.89 ± 0.17 U/mg, 48.30 ± 4.60 U/mg and 4.04 ± 0.12 μg/g respectively) with the administration of 5% PEF. The significant antimicrobial, antioxidant and anti-inflammatory activities support the positive correlation of PEF with its enhanced wound healing activity. PEF contains expressive amounts of total phenolic and total flavonoid contents (578.28 ± 2.30 mg GAE/g and 270.76 ± 2.52 mg QE/g). Of the various chemicals displayed in RP-UFLC-DAD analysis of PEF, gallic acid (68.08 μg/mg) and ethyl gallate (255.91 μg/mg) were predominant. The results indicate that PEF has great potential for the topical management of open wounds.

Deposition of calcium-containing minerals such as hydroxyapatite and whitlockite in the subretinal pigment epithelial (sub-RPE) space of the retina is linked to the development of and progression to the end-stage of age-related macular degeneration (AMD). AMD is the most common eye disease causing blindness amongst the elderly in developed countries; early diagnosis is desirable, particularly to begin treatment where available. Calcification in the sub-RPE space is also directly linked to other diseases such as Pseudoxanthoma elasticum (PXE). We found that these mineral deposits could be imaged by fluorescence using tetracycline antibiotics as specific stains. Binding of tetracyclines to the minerals was accompanied by increases in fluorescence intensity and fluorescence lifetime. The lifetimes for tetracyclines differed substantially from the known background lifetime of the existing natural retinal fluorophores, suggesting that calcification could be visualized by lifetime imaging. However, the excitation wavelengths used to excite these lifetime changes were generally shorter than those approved for retinal imaging. Here, we show that tetracycline-stained drusen in post mortem human retinas may be imaged by fluorescence lifetime contrast using multiphoton (infrared) excitation. For this pilot study, ten eyes from six anonymous deceased donors (3 female, 3 male, mean age 83.7 years, range 79–97 years) were obtained with informed consent from the Maryland State Anatomy Board with ethical oversight and approval by the Institutional Review Board.

Abstract Staphylococcus aureus is a major etiological agent of clinical and subclinical bovine mastitis. Owing to the mostly backyard dairy practices, we hypothesized that genetic diversity among mastitis-associated S. aureus from India would be high, and investigated 166 isolates obtained mostly from the Southern State of Karnataka, but also from a few other states. The results revealed (a) 8 to 13 fragments in pulsed-field gel electrophoresis (PFGE), forming 31 distinct patterns, and (b) 34 spa types, of which three (t17680, t18314, and t18320) were newly identified. Multi-locus sequencing typing (MLST) identified 39 sequence types (STs), with ST2454 (34.4%) and ST2459 (24%) being the most commonly represented, which clustered to clonal complexes (CC) CC9 and CC97, respectively; 12 STs were newly identified. Thirty-four (20.5%) of the 166 isolates displayed oxacillin resistance. On the other hand, whereas none were mecC+, 44 (26.5%) isolates were mecA+, with a predominance of SCCmecIVb (26/32 isolates, others being untypeable); 24 isolates (14.46%) were oxacillin-susceptible methicillin-resistant S. aureus (OS-MRSA; mecA+ but OS). Integrated analysis revealed that CC9-ST2454- and CC97-ST2459-SCCmecIVb were the predominant MRSA, although the distribution of CC9 and CC97 was similar between methicillin-resistant and -susceptible isolates. By PCR, 56.25%, 28.75% and 47.5% of the 166 isolates were positive for hlg, tsst and pvl genes, respectively. Our results, for the first time describe the application of a combination of various molecular methods to bovine mastitis-associated S. aureus isolates from India, corroborate the worldwide distribution of CC97 and CC9, and suggest pathogenic potential of the isolates.

Bi-objective school bus scheduling optimization problem that is a subset of vehicle fleet scheduling problem is focused in this paper. In the literature, school bus routing and scheduling problem is proven to be an NP-Hard problem. The processed data supplied by our framework is utilized to search a near-optimum schedule with the aid of reinforcement learning by evolutionary algorithms. They are named as reinforcement learning-enabled genetic algorithm (RL-enabled GA), reinforcement learning-enabled particle swarm optimization algorithm (RL-enabled PSO), and reinforcement learning-enabled ant colony optimization algorithm (RL-enabled ACO). In this paper, the performance characterization of reinforcement learning-enabled evolutionary algorithms for integrated school bus routing and scheduling problem is investigated. The efficiency of the conventional algorithms is improved, and the near-optimal schedule is achieved significantly in a shorter duration with the active guidance of the reinforcement learning algorithm. We attempt to carry out extensive performance evaluation and conducted experiments on a geospatial dataset comprising road networks, trip trajectories of buses, and the address of students. The conventional and reinforcement learning integrated algorithms are improving the travel time of buses and the students. More than 50% saving by the conventional and the reinforcement learning-enabled ant colony optimization algorithm compared to the constructive heuristic algorithm is achieved from 92nd and 54th iterations, respectively. Similarly, the saving by the conventional and the reinforcement learning-enabled genetic algorithm is 41.34% at 500th iterations and more than 50% improvement from 281st iterations, respectively. Lastly, more than 10% saving by the conventional and the reinforcement learning-enabled particle swarm algorithm is achieved from 432nd and 28th iterations, respectively.

Abstract A simple bioanalytical liquid chromatographic method was developed and validated to quantify letrozole (LTZ) in rat plasma. Protein precipitation using acidified chilled acetonitrile (containing 0.1% orthophosphoric acid) was used to extract LTZ from the plasma. Chromatographic separation was carried out on Kinetex C18 reverse phase (RP) column (250 mm × 4.6 mm i.d., 5 μm) using a mixture of 20 mM acetate buffer (pH 5.5) and acetonitirile (60:40 %v/v) eluting at 1.0 mL/min flow rate with the method responses measured at 240 nm. The optimized method was selective and established good linearity with recovery ranging between 91.16 and 99.44%. The validation experiments revealed that the method showed acceptable precision (2.61–7.48%) and accuracy (97.44–102.70%) and was found to be stable. The sensitivity of the method was demonstrated by the lowest concentration (LLOQ) detected at 75 ng/mL. Using the developed method, single-dose oral pharmacokinetics in Sprague-Dawley rats was carried out to successfully confirm the applicability of the method for the quantification of LTZ in biological matrix.

Purpose: Dengue fever (DF) epidemics in Singapore in 2005–2006 and 2007 were caused predominantly by dengue virus serotypes 1 (DENV-1) and 2 (DENV-2) respectively. We investigated the prevalence of ophthalmic manifestations during these consecutive epidemics. Methods: Seropositive DF patients admitted to the hospital during two separate dengue epidemics were enrolled from June 2005 to December 2007. Demographic, ophthalmic, and laboratory data were collected. The primary outcome measures were differences in ophthalmic and laboratory features across the two epidemics. Factors associated with increased risk of developing various DF-related ophthalmic manifestations were the secondary outcome measures. Results: Of the 115 patients enrolled, 109 (94.7%; 33 in 2005–2006 and 76 in 2007) completed the eye screening protocol. Majority of patients were Chinese (65, 59.6%) and males (81, 74.3%). The mean age was 40.8 years (range, 18–87). Colour vision impairment (12 vs 14 [36.4% vs 18.7%]; P ​= ​0.04), cotton wool spots (10 vs 3 [30.3% vs 3.9%]; P ​

Rabies is a fatal encephalomyelitis mainly transmitted to humans and other animals by rabid dog bites. Hence, vaccination programs are being instituted for the control of rabies in dogs. Though stray dogs have been vaccinated for years under various programs initiated for control of the disease, the effectiveness of these programs can be ascertained only by assessing the immunity of these dogs. With this in view, a study was conducted to assess the effectiveness of the ongoing mass dog vaccination (MDV) program by the Bengaluru City Municipal Corporation, Bengaluru, India. Whole blood and serum samples (n = 260) from vaccinated stray dogs in 26 wards of 8 corporation zones were tested by rapid fluorescent focus inhibition test (RFFIT) as well as an in-house quantitative indirect enzyme-linked immunosorbent assay (iELISA) for a humoral response and by interferon-gamma (IFN–γ) ELISA for a cellular response. As determined by the cut-off value of 0.5 IU/mL of serum, 71% and 87% of the samples from vaccinated dogs revealed adequate levels of antibodies presumed to confer protection by RFFIT and iELISA, respectively. The sensitivity and specificity of the iELISA were 100% and 63.3%, respectively. The IFN–γ ELISA revealed adequate cellular response in 50% of the samples. The quantitative iELISA was found to be useful in large-scale seromonitoring of MDV programs to aid in the elimination of dog-mediated rabies.

Downy mildew, a foliar disease caused by the oomycete Pseudoperonospora cubensis (Berk. and Curt.) Rostov, is one of the most destructive disease of cucumber (Cucumis sativus L.). Moderately resistant cultivars are available, but yield losses are high without the use of fungicides, therefore, higher levels of resistance are required to reduce the use of fungicides. Therefore, in the present study, 12 advance breeding lines along with susceptible check of cucumber were screened against downy mildew disease under natural field condition and artificial inoculation through seedling assay technique. The results confirmed that three lines namely IIHR-177-1-1-S7, IIHR-82-1-S6 and IIHR-81-1-S6 were found to be resistant with <10 per cent disease index (PDI) and significantly outperformed against check var. Swarna Agethi for yield and quality traits. These high yielding resistant lines can be utilized as one of the parents for the development of downy mildew resistant hybrids/varieties. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is being used in almost all aspects of life. The AI can assist medical consultants, primary health workers, and hospital administrators to understand analyze and interpret the medical data. The concepts such as data mining, image and signal processing, computer graphics, and machine learning are being utilized or being tried to implement in different health science areas such as dermatology, radiology, anesthesiology, psychiatry, surgery, and medical records . This article throws lights on some of the AI-related works that were carried out, especially in dermatology and radiology. This review has discussed its utility in other fields and the advantages such as faster execution, reliable results, and advantage over the manual process in certain aspects of healthcare. There are challenges, but further research and advances in technology in AI are likely to enormously benefit mankind.

Background and Aim: In recent times, non-aureus staphylococci (NAS) have emerged as the major organisms isolated from mastitis cases in dairy animals, with a predominance of Staphylococcus epidermidis and Staphylococcus chromogenes. As compared to Staphylococcus aureus, much less is known about the molecular types or the spatiotemporal epidemiology of these NAS species. In the present study, randomly amplified polymorphic DNA (RAPD) was employed to detect genetic polymorphisms, intraspecies diversity, and epidemiology of S. chromogenes strains (n=37) isolated from bovine and bubaline mastitis cases in the state of Karnataka. Materials and Methods: Thirty-seven S. chromogenes isolates (14 from bovines and 23 from bubaline) isolated from subclinical mastitis cases, from organized and unorganized sectors, were subjected to RAPD typing. Further, methicillin resistance was determined by cefoxitin disk diffusion method. Results: The amplified DNA fragments ranged from 150 to 3000 base pairs and yielded several RAPD profiles. Further analysis using Digital Image Correlation Engine correlation coefficient and UPGMA method showed that the 37 isolates could be classified into 12 distinct RAPD types (A to L) at 62% similarity (D=0.889). Four of the most predominant RAPD types, B, A, C, and E, in that order, and together, represented 65% of the isolates. High diversity was observed among the isolates both within farms and between geographic locations. Most of the isolates exhibited methicillin resistance. This is the first such report from India. Conclusion: In the absence of defined multilocus sequence type protocols or sufficient sequences available in the public domain, RAPD can be employed to determine genetic diversity of S. chromogenes isolates.

Abstract Background Tuberculosis remains one of the leading causes of morbidity and mortality worldwide. Therefore, understanding the pathophysiology of Mycobacterium tuberculosis is imperative for developing new drugs. Post-transcriptional regulation plays a significant role in microbial adaptation to different growth conditions. While the proteins associated with gene expression regulation have been extensively studied in the pathogenic strain M. tuberculosis H37Rv, post-transcriptional regulation involving small RNAs (sRNAs) remains poorly understood. Results We developed a novel moving-window based approach to detect sRNA expression using RNA-Seq data. Overlaying ChIP-seq data of RNAP (RNA Polymerase) and NusA suggest that these putative sRNA coding regions are significantly bound by the transcription machinery. Besides capturing many experimentally validated sRNAs, we observe the context-dependent expression of novel sRNAs in the intergenic regions of M. tuberculosis genome. For example, ncRv11806 shows expression only in the stationary phase, suggesting its role in mycobacterial latency which is a key attribute to long term pathogenicity. Also, ncRv11875C showed expression in the iron-limited condition, which is prevalent inside the macrophages of the host cells. Conclusion The systems level analysis of sRNA highlights the condition-specific expression of sRNAs which might enable the pathogen survival by rewiring regulatory circuits.

Aim: Comparative evaluation of Dentinal Element Incorporation, Interfacial Adaptation, and pH change induced by Bio-ceramic Sealer, mineral trioxide aggregate (MTA)-based sealer, and Epoxy Resin-based sealer. Materials and Methods: Freshly extracted eighty mandibular premolar teeth were divided into four groups (n = 20) based on the sealer used for obturation, i.e., AH Plus (Group I), Endoseal MTA (Group II), EndoSequence BC Sealer (Group III), or Unfilled, unimmersed (Group IV), which served as the control. Specimens of Group I, II, and III were immersed in calcium and magnesium-free phosphate-buffered saline for 7 days. Specimens were sectioned longitudinally, and the ultrastructure of the dentine material interface and the elemental incorporation in the interfacial layer was analyzed using a wavelength dispersive scanning electron microscope-X-ray spectroscopy electron probe microanalyzer (SEM). The interfacial adaptation was measured using SEM. pH was calculated using pH meter. Statistical Analysis: Data were statistically analyzed using one-way ANOVA and Duncan's multiple range tests. Results: At the interface, both bio-ceramic materials formed a tag-like structure rich in calcium and silicon deposits, which were significantly higher in EndoSequence and Endoseal MTA, respectively. Endosequence BC sealer showed fewer interfacial gaps and the highest pH change as compared to the other groups. Conclusions: Bio-ceramic sealers showed better interfacial adaptation, element incorporation in the interfacial layer, and increased alkalinity of pH, leading to a superior marginal seal as compared to AH Plus and the control group.

There is an increased risk of debilitating illnesses that often have no curative treatment with aging. The mainstay of treatment in many such conditions is palliative care: a holistic approach focused on preventing and relieving physical, psychosocial, legal, ethical, and spiritual problems. It involves the facilitation of end-of-life care decisions aimed at relieving distress and improving quality of life. In this article, the authors discuss the role of mental health professionals in legal issues related to palliative care in the elderly around decision-making, right to autonomy, euthanasia, and advanced directive. The cognitive decline associated with aging and mental health issues in the palliative care setting of an individual such as dementia, depression, and hopelessness, and impact on the family members like burnout may influence the overall capacity of that individual to make decisions about their treatment. While an individual has a right to self-determination and autonomy, withholding or withdrawing treatment has many legal and ethical implications, more so in those with incapacity, especially in India due to the absence of uniform legislation. The decision to withhold or withdraw treatment might be a restrictive choice due to limited options in a setting with a lack of palliative care options, poor psychosocial support, nonaddress of mental health issues, and lack of awareness. As the right to health is a constitutional right, and the right to mental health is legally binding under Section 18 of the Mental Health Care Act 2017, systematic efforts should be made to scale up services and reach out to those in need.

Mental health issues impair decision-making capacity, more so in elderly people. Impaired decision-making capacity can make person unfit to enter into various civil deeds and agreements. Such civil deeds can include guardianship, property transaction, holding a bank account, having voting rights, making a will, donating an organ, etc. This article focuses on importance of mental health in entering into above-mentioned civil agreements, how to do assessments to determine if one is fit to enter into civil agreements, and what are the legal ways in which a person can avail help to execute his/her civil rights even when affected by mental health issues.

With prolonged therapy and increased instances of drug resistance, tuberculosis is viewed as a serious infectious disease causing high mortality. Emerging concepts in Mycobacterium tuberculosis pathogenicity include biofilm formation, which endows bacterial survival in the host for a long time. To tackle chronic tuberculosis infection, a detailed understanding of the bacterial survival mechanisms is crucial. Using comparative genomics and literature mining, 115 M. tuberculosis proteins were shortlisted for their likely association with biofilm formation or quorum sensing. These include essential genes such as secA2, lpqY-sugABC, Rv1176c, and Rv0195, many of which are also known virulence factors. Furthermore, the functional relationship among these proteins was established by considering known protein-protein interactions, regulatory interactions, and gene expression correlation data/information. Graph centrality and motif analyses predicted the importance of proteins, such as Rv0081, DevR, RegX3, Rv0097, and Rv1996 in M. tuberculosis biofilm formation. Analysis of conservation across other biofilm-forming bacteria suggests that most of these genes are conserved in mycobacteria. As the processes, such as quorum sensing, leading to biofilm formation involve diverse pathways and interactions between proteins, these system-wide studies provide a novel perspective toward understanding mycobacterial persistence.

Forests of the Western---- Ghats are well known for their evergreenness and high endemism. The present study carried out in the Sharavathi River Basin in the central Western Ghats of India is to find the relationship between forest evergreenness and tree endemism. The study was carried out from 2000 to 2006 and the methodology followed is a combination of transect and quadrat method nested with smaller quadrats for shrub layer and herb layer. A total of 51 endemic tree species belonging to 20 families were recorded. The results reveal that the composition of endemic tree population is closely associated with the evergreenness of the forest. With the increase in evergreenness, endemism also increased and almost all the endemic trees of the region occurred in very high evergreen class. Many of them were exclusively found in very high evergreen forests and ground layer data support this observation. Such narrow distribution of endemics makes them most vulnerable to extinction. The present study will be helpful in understanding the association of endemic trees with evergreenness of forest and will be useful in conservation as well as restoration of these endemic trees in their natural habitats.

Introduction: Chronic obstructive pulmonary disease (COPD) is a common preventable and treatable disease characterized by progressive airflow limitation and associated with enhanced chronic inflammatory response of the airways to a variety of noxious stimuli. The current concept of COPD, however, extends beyond the respiratory system to include a variety of extrapulmonary manifestations which includes raised inflammatory markers. Methods: This was a single, center observational open-labeled case–controlled study which included fifty patients of diagnosed COPD and 50 age- and gender-matched controls. All patients were evaluated by detailed history taking, pulmonary function test, 6-min walk test, and calculation of BODE scores. Levels of serum inflammatory markers such as cortisol, tumor necrosis factor alpha, interleukin-6 (IL-6), lactate dehydrogenase, and C-reactive protein were estimated using standard quality equipments. Observations: Majority of the patients in the study and control groups were males and were aged above 40 years. Thirty-eight of the fifty COPD patients had BODE scores of more than 3. All the studied inflammatory markers were significantly higher in the COPD group as compared to the control group. Of all the studied markers, only IL-6 showed a significant correlation with BODE index, i.e., higher IL-6 values were associated with higher BODE scores. No correlation was seen between the other markers and BODE scores. Conclusions: Our data suggest that IL-6 is a biomarker that correlates with BODE score. IL-6 as a target for therapy in COPD needs to be further studied. Follow-up studies are needed to validate findings.

Japanese encephalitis (JE) is a serious public health concern in most of Asia. The disease is caused by JE virus (JEV), a flavivirus transmitted by Culex mosquitoes. Several vaccines have been developed to control JE in endemic areas as well as to protect travelers and military personnel who visit or are commissioned from non-endemic to endemic areas. The vaccines include inactivated vaccines produced in mouse brain or cell cultures, live attenuated vaccines, and a chimeric vaccine based on the live attenuated yellow fever virus 17D vaccine strain. All the marketed vaccines belong to the JEV genotype III, but have been shown to be efficacious against other genotypes and strains, with varying degrees of cross-neutralization, albeit at levels deemed to be protective. The protective responses have been shown to last three or more years, depending on the type of vaccine and the number of doses. This review presents a brief account of the different JE vaccines, their immunogenicity and protective ability, and the impact of JE vaccines in reducing the burden of disease in endemic countries.

Abstract Clinical genetics laboratories have recently adopted guidelines for the interpretation of sequence variants set by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP). The use of in silico algorithms to predict whether amino acid substitutions result in human disease is inconsistent across clinical laboratories. The clinical genetics community must carefully consider how in silico predictions can be incorporated into variant interpretation in clinical practice. Please see related Research article: https://doi.org/10.1186/s13059-017-1353-5