Serum vitamin D levels in children with vernal keratoconjunctivitis - A study from a tertiary care pediatric hospital of North India.

BACKGROUND: To study the levels of vitamin D serum levels in children with vernal keratoconjuctivits (VKC) and comparing vitamin D levels in after giving vitamin D supplements between intervention and control group. METHODS: The study was conducted in population between 1 to 12 years in tertiary care hospital in North India. Amongst children with VKC, full ocular examination along with Boninis clinical grading of VKC and serum vitamin D levels were assessed. Whole study group was randomly divided into two groups. Intervention group had received vitamin D powder while control group kept under observation. RESULTS: A total of 88 children received vitamin D supplementation and 39 kept in control group. CONCLUSION: Our study suggests that children in intervention group showed improvement in serum vitamin D levels with the clinical improvement in VKC grading too.

Emerging challenges in antimicrobial resistance: implications for pathogenic microorganisms, novel antibiotics, and their impact on sustainability.

Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.

Assessment for Diabetic Neuropathy: Treatment and Neurobiological Perspective.

Diabetic neuropathy, also known as diabetic peripheral sensorimotor neuropathy (DPN), is a consequential complexity of diabetes, alongside diabetic nephropathy, diabetic cardiomyopathy, and diabetic retinopathy. It is characterized by signs and symptoms of peripheral nerve damage in diabetes patients after ruling out other causes. Approximately 20% of people with diabetes are affected by this painful and severe condition. The development of diabetic neuropathy is influenced by factors such as impaired blood flow to the peripheral nerves and metabolic issues, including increased polyol pathway activation, myo-inositol loss, and nonenzymatic glycation. The present review article provides a brief overview of the pathological changes in diabetic neuropathy and the mechanisms and types of DPN. Various diagnostic tests and biomarkers are available to assess nerve damage and its severity. Pharmacotherapy for neuropathic pain in diabetic neuropathy is complex. This review will explore current treatment options and potential future developments to improve the quality of life for patients suffering from diabetic neuropathy.

Development of a Visually Calculated SUVmean (HIT Score) on Screening PSMA PET/CT to Predict Treatment Response to 177Lu-PSMA Therapy: Comparison with Quantitative SUVmean and Patient Outcomes.

177Lu-PSMA therapy is an effective treatment in patients with metastatic castration-resistant prostate cancer. SUVmean is a valuable screening biomarker to assess the suitability for 177Lu-PSMA therapy but requires quantitative software. This study aims to develop a simple, clinically applicable prostate-specific membrane antigen PET/CT score that encompasses the elements of SUVmean without requiring additional quantification. Methods: Datasets from ethics-approved trials of patients with metastatic castration-resistant prostate cancer after androgen receptor signaling inhibition and taxane chemotherapy (or unfit for taxane), who were treated with 177Lu-PSMA-617 and 177Lu-PSMA I&T with a pretreatment screening with 68Ga-PSMA-11 PET/CT, and clinical outcome data, including a prostate-specific antigen (PSA) 50% response rate (PSA50), PSA progression-free survival (PSA-PFS), and overall survival (OS), were included. The screening 68Ga-PSMA-11 PET/CT of all participants was analyzed both semiquantitatively and visually. Semiquantitative analysis was used to derive the SUVmean Visual analysis of the 68Ga-PSMA-11 PET/CT images involved a binary visual heterogeneity assessment (homogeneous or heterogeneous), allocating a tumor SUVmax range (<15, 15-29, 30-49, 50-79, or ≥80). A 4-category score incorporating both heterogeneity and intensity of tumors (HIT) was then developed as a combination of heterogeneity and intensity (SUVmax range). The SUVmax was less than 15 for score 1, 15-79 with heterogeneous intensity for score 2, 15-79 with homogeneous intensity for score 3, and 80 or greater for score 4. This score was evaluated according to clinical outcomes (PSA50, PSA-PFS, and OS) and compared with SUVmean Results: Data from 139 participants were analyzed. In total, 75 (54%) patients achieved a PSA50 with a median PSA-PFS of 5.5 mo (95% CI, 4.1-6.0 mo) and an OS of 13.5 mo (95% CI, 11.1-17.9 mo). SUVmean was associated with PSA50 and survival outcomes when analyzed as a continuous variable or as quartiles. The PSA50 for HIT scores 1-4 was 0%, 39%, 65%, and 76%, respectively. The HIT score was strongly related to PSA-PFS and OS (log-rank test, P < 0.001 and P = 0.002). The median PSA-PFS for HIT scores 1-4 was 1.0, 4.1, 6.0, and 8.5, respectively, and the median OS was 7.6, 12.0, 18.5, and 16.9 mo, respectively. Cohen κ between readers for the HIT score was 0.71. Conclusion: A prostate-specific membrane antigen PET/CT score incorporating HIT derived from tools on a standard PET workstation is comparable with quantitative SUVmean as a prognostic tool following 177Lu-PSMA therapy.

Supplementation of probiotic Bifidobacterium breve Bif11 reverses neurobehavioural deficits, inflammatory changes and oxidative stress in Parkinson's disease model.

Human gut microbiota are thought to affect different physiological processes in the body, including brain functions. Gut dysbiosis has been linked to the progression of Parkinson's disease (PD) and thus, restoring the healthy gut microbiota with supplementation of putative probiotic strains can confer some benefits in PD. In the current study, we explored the neuroprotective potential of Bifidobacterium breve Bif11 supplementation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated female Sprague Dawley rats. This study investigated the behavioural, molecular and biochemical parameters in the MPTP rat model. A pharmacological intervention of Bif11 at doses of 1 × 1010 CFU and 2 × 1010 CFU for 21 days was found to attenuate the cognitive and motor changes in the MPTP rat model. Furthermore, it also increased the tyrosine hydroxylase levels, reduced pro-inflammatory markers and decreased oxidative and nitrosative stress in the mid brain of MPTP-lesioned rats. Bif11 supplementation even restored the levels of short-chain fatty acids and decreased intestinal epithelial permeability in MPTP-induced PD model rats. In summary, these findings demonstrate that B. breve Bif11 has the potential to ameliorate symptoms of PD. However, this therapy needs to be further investigated with in-depth mechanistic insights in the future for the treatment of PD.

Structure-guided discovery of anti-CRISPR and anti-phage defense proteins.

Bacteria use a variety of defense systems to protect themselves from phage infection. In turn, phages have evolved diverse counter-defense measures to overcome host defenses. Here, we use protein structural similarity and gene co-occurrence analyses to screen >66 million viral protein sequences and >330,000 metagenome-assembled genomes for the identification of anti-phage and counter-defense systems. We predict structures for ~300,000 proteins and perform large-scale, pairwise comparison to known anti-CRISPR (Acr) and anti-phage proteins to identify structural homologs that otherwise may not be uncovered using primary sequence search. This way, we identify a Bacteroidota phage Acr protein that inhibits Cas12a, and an Akkermansia muciniphila anti-phage defense protein, termed BxaP. Gene bxaP is found in loci encoding Bacteriophage Exclusion (BREX) and restriction-modification defense systems, but confers immunity independently. Our work highlights the advantage of combining protein structural features and gene co-localization information in studying host-phage interactions.

Yield of coeliac screening in children with non-specific functional abdominal pain: A cross-sectional study from North India.

A significant group of children suffer from non-specific functional abdominal pain. We argue that the prevalence of coeliac disease is higher in this group than the general population; thus, screening in this group is justified.

Transcriptomics analysis of allergen-induced inflammatory gene expression in the Four-Core Genotype mouse model.

Sex differences in allergic inflammation have been reported, but the mechanisms underlying these differences remain unknown. Contributions of both sex hormones and sex-related genes to these mechanisms have been previously suggested in clinical and animal studies. Here, Four-Core Genotypes (FCG) mouse model was used to study the inflammatory response to house dust mite (HDM) challenge and identify differentially expressed genes (DEGs) and regulatory pathways in lung tissue. Briefly, adult mice (8-10 wk old) of the FCG (XXM, XXF, XYM, XYF) were challenged intranasally with 25 µg of HDM or vehicle (PBS-control group) 5 days/wk for 5 wk (n = 3/10 group). At 72 h after the last exposure, we analyzed the eosinophils and neutrophils in the bronchoalveolar lavage (BAL) of FCG mice. We extracted lung tissue and determined DEGs using Templated Oligo-Sequencing (TempO-Seq). DEG analysis was performed using the DESeq2 package and gene enrichment analysis was done using Ingenuity Pathway Analysis. A total of 2,863 DEGs were identified in the FCG. Results revealed increased eosinophilia and neutrophilia in the HDM-treated group with the most significantly expressed genes in XYF phenotype and a predominant effect of female hormones vs. chromosomes. Regardless of the sex hormones, mice with female chromosomes had more downregulated genes in the HDM group but this was reversed in the control group. Interestingly, genes associated with inflammatory responses were overrepresented in the XXM and XYF genotypes treated with HDM. Sex hormones and chromosomes contribute to inflammatory responses to HDM challenge, with female hormones exerting a predominant effect mediated by inflammatory DEGs.NEW & NOTEWORTHY Gene expression profiling helps to provide deep insight into the global view of disease-related mechanisms and responses to therapy. Using the Four-Core Genotype mouse model, our findings revealed the influence of sex hormones and sex chromosomes in the gene expression of lungs exposed to an aeroallergen (House Dust Mite) and identified sex-specific pathways to better understand sex disparities associated with allergic airway inflammation.

Lung proinflammatory microRNA and cytokine expression in a mouse model of allergic inflammation: role of sex chromosome complement and gonadal hormones.

Epigenetic alterations such as dysregulation of miRNAs have been reported to play important roles in interactions between genetic and environmental factors. In this study, we tested the hypothesis that induction of lung inflammation by inhaled allergens triggers a sex-specific miRNA regulation that is dependent on chromosome complement and hormonal milieu. We challenged the four core genotypes (FCGs) model through intranasal sensitization with a house dust mite (HDM) solution (or PBS as a control) for 5 wk. The FCG model allows four combinations of gonads and sex chromosomes: 1) XX mice with ovaries (XXF), 2) XY mice with testes (XYM), 3) XX mice with testes (XXM), and 4) XY mice with ovaries (XYF). Following the challenge (n = 5-7/group), we assessed the expression of 84 inflammatory miRNAs in lung tissue using a PCR array and cytokine levels in bronchoalveolar lavage fluid (BAL) by a multiplex protein assay (n = 4-7 animals/group). Our results showed higher levels of the chemokine KC (an Il-8 homolog) and IL-7 in BAL from XYF mice challenged with HDM. In addition, IL-17A was significantly higher in BAL from both XXF and XYF mice. A three-way interaction among treatment, gonads, and sex chromosome revealed 60 of 64 miRNAs that differed in expression depending on genotype; XXF, XXM, XYF, and XYM mice had 45, 32, 4, and 52 differentially expressed miRNAs, respectively. Regulatory networks of miRNAs identified in this study were implicated in pathways associated with asthma. Female gonadal hormonal effects may alter miRNA expression and contribute to the higher susceptibility of females to asthma.NEW & NOTEWORTHY miRNAs play important roles in regulating gene and environmental interactions. However, their role in mediating sex differences in allergic responses and lung diseases has not been elucidated. Our study used a targeted omics approach to characterize the contributions of gonadal hormones and chromosomal components to lung responses to an allergen challenge. Our results point to the influence of sex hormones in miRNA expression and proinflammatory markers in allergic airway inflammation.

Subcuticular skin closure at cesarean delivery with poliglecaprone-25 vs polyglactin-910: a randomized controlled trial.

BACKGROUND: Cesarean delivery is a commonly performed surgical procedure worldwide. There is limited good-quality evidence regarding subcuticular skin closure with absorbable sutures in transverse incisions after cesarean delivery. OBJECTIVE: This study aimed to compare poliglecaprone-25 (3-0) and polyglactin-910 (4-0) sutures for subcuticular skin closure in Pfannenstiel incisions among women undergoing cesarean delivery. STUDY DESIGN: In this double-blind, single-center, randomized controlled trial among women undergoing cesarean delivery (elective and emergency), 200 women were randomized (Group 1-subcuticular skin closure with poliglecaprone-25 [3-0] vs Group 2-subcuticular skin closure with polyglactin-910 [4-0]). All women received similar preoperative and postoperative care. A sample size of 200 women was selected with the aim of reducing the composite wound complication rate from 15.8% to 3.6% with a power of 0.80 and a 2-tailed α of 0.05. Thus, 90 women were required in each group, but 100 were selected to account for attrition. RESULTS: Composite wound complications (including surgical site infection, hematoma, seroma, need for resuturing or readmission for wound complications) were similar in the 2 groups (Group 1 vs 2: 16 vs 10; P=.293; relative risk, 1.28; 95% confidence interval, 0.91-1.79). Surgical site infection (8 vs 7; P=1.000; relative risk, 1.08; 95% confidence interval, 0.64-1.83), hematoma (1 vs 2; P=.561; relative risk, 0.66; 95% confidence interval, 0.13-3.31), seroma (8 vs 2; P=.052; relative risk, 1.65; 95% confidence interval, 1.17-2.33), need for resuturing (4 vs 3; P=.700; relative risk, 1.15; 95% confidence interval, 0.60-2.22), and need for readmission (4 vs 4; P=1.000) were similar in the 2 groups. Pain score on the visual analog scale at 3 days (3.2±1.0 vs 3.6±1.2) and 6 weeks after operation (1.6±0.8 vs 1.7±0.9;) was significantly lower in Group 1 (P=.023 and P=.033, respectively). There was no difference between observer and patient scar assessment scores measured at 6 weeks after operation (P=.069 and P=.431, respectively). CONCLUSION: Poliglecaprone-25 (3-0) and polyglactin-910 (4-0) subcuticular sutures were comparable regarding composite wound complications (surgical site infection, hematoma, seroma, wound separation or re-suturing, need for readmission) and cosmetic appearance (patient scar assessment score & observer scar assessment score) related to skin closure among women undergoing cesarean delivery through a Pfannenstiel incision in nonobese women (average body mass index, 25).

Genome-wide transcriptional profiling and physiological investigation elucidating the molecular mechanism of multiple abiotic stress response in Stevia rebaudiana Bertoni.

Considering the major source of plant-derived low/non-calorie steviol glycosides (SGs), comprehensive physiological, biochemical, and deep transcriptional investigations were conducted to explicit deeper insight into multiple abiotic stress responses in Stevia rebaudiana. The physiological indicators including photosynthesis, chlorophyll, relative water content, shoot growth, electrolyte leakage, and SG biosynthesis were negatively impacted under drought (DS), followed by salinity (SS) and waterlogging (WS). Global transcriptional analysis revealed significant upregulated expression of the genes encoding for ROS detoxification (GST, SOD, APX, glutathione peroxidase), osmotic adjustment (alpha-trehalose-phosphate and S-adenosylmethionine decarboxylase), ion transporters (CAX, NHX, CNGS, VPPase, VATPase), water channel (PIP1, TIP) and abiotic stress-responsive candidate genes (LEA, HSPs, and Dehydrins) regulating abiotic stress response in S. rebaudiana. These inferences were complemented with predicted interactome network that revealed regulation of energy metabolism by key stress-responsive genes (GST, HKT1, MAPKs, P5CSs, PIP), transcription factors (HSFA2, DREB1A, DREB2A), and abiotic stress responsive pathways (ABA, ethylene, ion stress). This is the first detailed study to comprehend the molecular regulation of stress response and their interplay under DS, SS, and WS. The key genes and regulators can be functionally validated, and will facilitate targeted gene editing for genetic improvement of crop sustainability under changing environmental conditions in S. rebaudiana.

Evaluation of Human Dental Plaque Lactic Acid Bacilli for Probiotic Potential and Functional Analysis in Relevance to Oral Health.

Members of the lactic acid bacillus group are well-known probiotics and primarily isolated from fermented food, dairy products, intestinal and gut environment of human. Since probiotics from the human source are preferred, there exists a huge repertoire of lactobacilli in the human oral cavity which could prove a much better niche to be exploited for these beneficial microorganisms. Therefore, in this study, four lactobacilli strains, including strain DISK7, reported earlier, isolated from dental plaque samples of a healthy humans were evaluated for their probiotic potential. Strains displayed 99.9% of 16S rRNA gene sequence identity with species of the genera Lactobacillus and Limosilactobacillus. All strains showed lactic acid production, tolerance to low pH and antibiotic sensitivity. Variations were observed among strains in their aggregation ability, biofilm formation, bile salt resistance and cholesterol degradation. Further, we analyzed the interaction of strains with other oral commensals and opportunistic pathogens in co-culture experiments. Isolates DISK7 and DISK26 exhibited high co-aggregation (> 70%) with secondary colonizers, Streptococcus pyogenes and Veillonella parvula, respectively, but their aggregation ability was decreased with opportunistic pathogens. Furthermore, strains showed a substantial increase in biofilm in co-culture with other Lactobacillus isolates, indicating their ability to proliferate commensal bacteria in the oral environment. These microbes continually evolve in terms of niche adaptation as evidenced in genome analysis. The highlight of the investigation is the isolation and evaluation of the probiotic lactobacilli from the human oral cavity, which could prove a much better niche to be exploited for the effective commercialization of these beneficial microbes. Taken together, probiotic properties and interaction with commensal bacteria, these isolates exhibit the huge potential to be developed as alternative bioresource agents for maintenance of oral health. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01108-2.

Applicability of mesenchymal stem cell-derived exosomes as a cell-free miRNA therapy and epigenetic modifiers for diabetes.

Given that exosome nanovesicles constitute various growth factors, miRNAs and lncRNAs, they have implications for epigenetic modifications. Few studies have shown that exosomes from mesenchymal stem cells (MSCs) exhibit therapeutic effects on diabetic complications by substituting miRNAs and regulating histone modifications. Therefore, reversing epigenetic aberrations in diabetes may provide new insight into its treatment. This review discusses the impact of DNA and histone methylations on the development of diabetes and its complications. Further, we talk about miRNAs dysregulated in diabetic conditions and the possibility of utilizing mesenchymal stem cell (MSC) exosomes for the development of miRNA cell-free therapy and epigenetic modifiers in reversing diabetic-induced epigenetic alterations.

Immunomodulatory action of synbiotic comprising of newly isolated lactic acid producing bacterial strains against allergic asthma in mice.

Given the reported role of gut-microbiota in asthma pathogenesis, the present work was carried to evaluate immunomodulatory action of newly isolated lactic acid producing bacterial strains Bifidobacterium breve Bif11 and Lactiplantibacillus plantarum LAB31 against asthma using ovalbumin (OVA) based mouse model. Our results show that both strains modulate Th2 immune response potentially through production of short chain fatty acids (SCFAs), resulting in suppression of OVA-induced airway inflammation. Furthermore, synbiotic comprising of both strains and prebiotic, Isomaltooligosaccharide exhibited superior potential in amelioration of OVA-induced airway inflammation through improved modulation of Th2 immune response. Further, synbiotic protects against OVA-induced mucus hyper-production and airway-hyperresponsiveness. Such protection was associated with normalization of gut microbiome and enhanced production of SCFAs in cecum which correlates closely with population of T-regulatory cells in spleen. Overall, our novel synbiotic possesses the ability to fine-tune the immune response for providing protection against allergic asthma.

Dengue havoc: overview and eco-friendly strategies to forestall the current epidemic.

Dengue fever is a mosquito-borne viral illness that affects over 100 nations around the world, including Africa, America, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Those who get infected by virus for the second time are at greater risk of having persistent dengue symptoms. Dengue fever has yet to be treated with a long-lasting vaccination or medication. Because of their ease of use, mosquito repellents have become popular as a dengue prevention technique. However, this has resulted in environmental degradation and harm, as well as bioaccumulation and biomagnification of hazardous residues in the ecosystem. Synthetic pesticides have caused a plethora of serious problems that were not foreseen when they were originally introduced. The harm caused by the allopathic medications/synthetic pesticides/chemical mosquito repellents has paved the door to employment of eco-friendly/green approaches in order to reduce dengue cases while protecting the integrity of the nearby environment too. Since the cases of dengue have become rampant these days, hence, starting the medication obtained from green approaches as soon as the disease is detected is advisable. In the present paper, we recommend environmentally friendly dengue management strategies, which, when combined with a reasonable number of vector control approaches, may help to avoid the dengue havoc as well as help in maintaining the integrity of the ecosystem.

Chemistry and Therapeutic Aspect of Triazole: Insight into the Structure-activity Relationship.

The triazole ring is a highly significant heterocycle that occurs naturally in many commodities and is a common feature in pharmaceuticals. Recently, heterocyclic compounds and their derivatives have been getting a lot of attention in medicinal chemistry because they have a lot of pharmacological and biological potential. For example, a lot of drugs have nitrogen-containing heterocyclic moieties. The triazole ring is often used as a bio-isostere of the oxadiazole nucleus. The oxygen atom in the oxadiazole nucleus is replaced by nitrogen in the triazole analogue. This article explores the pharmacological properties of the triazole moiety, including but not limited to antibacterial, analgesic, anticonvulsant, anthelmintic, anti-inflammatory, antitubercular, antimalarial, antioxidant, antiviral, and other properties. Additionally, we discuss the diverse multi- target pharmacological activities exhibited by triazole-based compounds. Based on a literature review, it is evident that triazole-based chemicals hold significant potential for various applications.

Combined Thermodynamic, Theoretical, and Biological Study for Investigating N-(2-Acetamido)iminodiacetic Acid as a Potential Thorium Decorporation Agent.

The most effective approach to mitigate the toxic effects of internal exposure of radiometals to humans is metal-ligand (ML) chelation therapy. Thorium (Th)-induced carcinogenesis as well as other health hazards to humans as a result of chronic internal exposure necessitates the development of efficient Th-decorporating agents. In this regard, chemical and biological studies were carried out to evaluate N-(2-Acetamido)iminodiacetic acid (ADA), a comparatively cost-effective, readily available, and biologically safe complexing agent for Th decorporation. In the present work, detailed thermodynamic studies for complexation of ADA with Th(IV) have been carried out to understand Th-ADA interaction, using potentiometry, calorimetry, electrospray ionization mass spectrometry, and theoretical studies, followed by its biological assessment for Th decorporation. Thermodynamic studies revealed the formation of strong Th-ADA complexes, which are enthalpically as well as entropically favored. Interestingly, density functional theory calculations, to obtain a thermodynamically favored mode of coordination, showed the uncommon trend of lower denticity of ADA in ML than in ML2, which has been explained on the basis of stabilization of ML by hydrogen bonding. The same was also reflected in the unusual trend of enthalpy for Th-ADA complexes. Biological experiments using human erythrocytes, whole human blood, and lung cells showed good cytocompatibility and ability of ADA to significantly prevent Th-induced hemolysis. Th removal of ADA from erythrocytes, human blood, and normal lung cells was found to be comparable with that of diethylenetriamine pentaacetate (DTPA), an FDA approved decorporating agent. The present study contributed significant data about Th complexation chemistry of ADA and its Th decorporation efficacy from human erythrocytes, blood, and lung cells.

Prevalence and Predictors of Vitamin B12 Deficiency in Children with Severe Acute Malnutrition, and its Association with Development.

OBJECTIVES: To determine the proportion of children with severe acute malnutrition (SAM) having vitamin B12 deficiency, its clinical predictors, and its association with development. METHODS: In this cross-sectional study, 100 children between 1 mo to 59 mo [mean (SD) age 17 (12.75) mo; 55 males], with diagnosis of SAM as per WHO criteria, were included. Serum vitamin B12, serum folate, and serum ferritin levels were measured by chemiluminescence immunometric assay method, while serum Homocysteine (Hcy) level was measured by enzymatic cycling method. Development assessment was done by Denver Development Screening Tool (DDST-II). RESULTS: The mean (SD) serum vitamin B12 (cobalamin) levels were 296.52 (246.95) pg/mL; 45% children were vitamin B12 deficient (<203 pg/mL). Hyperhomocysteinemia (>14 µmol/L) was present in 39 (39%), and among these 69% (27/39) children had concomitant low serum vitamin B12 levels. Severe anemia and hypoproteinemia were significantly and independently associated with vitamin B12 deficiency [aOR (95% CI) 3.22 (1.13, 10) and 10 (1.66, 58.82), respectively]. Out of 45 children who were vitamin B12 deficient, 93%, 87%, 62% and 80% had gross motor, fine-motor, language and adaptive-cognitive delay, respectively. Vitamin B12 level was significantly associated (P <0.001) with developmental delay. CONCLUSIONS: There is a high prevalence of vitamin B12 deficiency in children with SAM, which is also associated with development delay across all domains (except language) in these children.

State-space modeling approach for fringe pattern demodulation.

A spatial carrier fringe demodulation technique is proposed based on a state-space modeling approach for phase estimation. The fringe background intensity, carrier frequency, and phase quadrature components are considered to be the elements of the state vector, which are estimated simultaneously. The state estimation is performed using the extended Kalman filter. The simulation and experimental results are provided to demonstrate the performance comparison of the proposed method with popular and state-of-the-art methods in terms of noise robustness and phase estimation accuracy.

Insights into the role of the conserved GTPase domain residues T62 and S277 in yeast Dnm1.

Mitochondrial division is a highly regulated process. The master regulator of this process is the multi-domain, conserved protein called Dnm1 in yeast. In this study, we systematically analyzed two residues, T62 and S277, reported to be putatively phosphorylated in the GTPase domain of the protein. These residues lie in the G2 and G5 motifs of the GTPase domain. Both residues are important for the function of the protein, as evident from in vivo and in vitro analysis of the non-phosphorylatable and phosphomimetic variants. Dnm1T62A/D and Dnm1S277A/D showed differences with respect to the protein localization and puncta dynamics in vivo, albeit both were non-functional as assessed by mitochondrial morphology and GTPase activity. Overall, the secondary structure of the protein variants was unaltered, but local conformational changes were observed. Interestingly, both Dnm1T62A/D and Dnm1S277A/D exhibited dominant-negative behavior when expressed in cells containing endogenous Dnm1. To our knowledge, we report for the first time a single residue (S277) change that does not alter the localization of Dnm1 but makes it non-functional in a dominant-negative manner. Intriguingly, the two residues analyzed in this study are present in the same domain but exhibit variable effects when mutated to alanine or aspartic acid.