Effect of coconut and sesame oils on gingivitis.

The effectiveness of Oil Pulling Therapy (OPT) with coconut (CO) and sesame oil (SO) on gingivitis patients is of interest. Forty patients were randomly distributed into group A and B for CO and SO respectively. Participants of group A were explained in detail about the OPT with CO and group B with SO along with their routine oral hygiene practice for 30 days. The mean plaque index of CO and SO reduced from 1.5 to 1.32 and 1.65 to 1.36 (p<0.05) respectively after 30 days. The mean gingival index of CO and SO declined from 1.12 to 0.9 and 1.1 to 0.81 respectively after 30 days (p<0.05) compared to initial scores. The mean no. of colonies in the case of CO and SO declined from 35.8 x 103 to 32.4 x 103 and 6.8 x 103 to 34.6 x 103 after 30 days (p<0.05). OPT reduced plaque and gingivitis, according to the results of one month. Hence, we must increase awareness about oil pulling, as this home therapy can prevent gingival diseases in countries with limited resources like ours.

Presenting Pattern and Psychiatric Comorbidities in Rural versus Urban Substance Dependent Patients: A Hospital-Based Cross-Sectional Study.

Background: "Locality" is a significant factor in substance initiation, maintenance, and relapse. The pattern of substance dependence among rural and urban populations varies across studies and is scarcely studied, warranting further research. To compare presenting patterns (sociodemographic and drug-related variables), reasons for substance use, and psychiatric comorbidities (prevalence, type, and severity) between rural and urban substance-dependent groups. Materials and Methods: This study was a cross-sectional analytical study in a government de-addiction center, including rural and urban patient groups aged 18-65. International Classification of Diseases, Tenth Revision (ICD-10) criteria, and severity of dependence scale were used for diagnosing substance dependence. After detoxification, psychiatric comorbidity was assessed using brief psychiatric rating scale, Young's mania rating scale, and patient health questionnaire - somatic, anxiety, and depression symptoms scale. Post-analysis was performed to assess socioeconomic variables and access to de-addiction services. Results: The final sample was 500 (250 rural and 250 urban). The post-analysis sample size was 386 (211 rural and 175 urban). The mean age was 38.2 ± 12.4 years, mostly males (n = 495, 99%). Substance frequency was opioids (92%)> benzodiazepines (24.8%) > alcohol (22%) > cannabis (1.6%) for rural and opioids (91.2%) > alcohol (29.6%) > benzodiazepines (14.8%) > cannabis (2%) for urban patients. More than half of patients had comorbid nicotine dependence. Rural patients were more benzodiazepine dependent (P = 0.007), and urban were more opioid + alcohol dependent (P = 0.001). Rural patients had higher age (P = 0.012), less education (P < 0.001), positive family history of substance (P = 0.028), daily wagers, and farmers (P < 0.001) than urban patients who were younger, students (P = 0.002), businessmen and government employed (P < 0.001). Urban patients expended more on drugs (P < 0.001), had higher treatment attempts (P = 0.008), and had better availability and accessibility of de-addiction services (P < 0.001). More rural users initiated substances to "enhance performance," whereas urban ones initiated for "stress relief/novelty" (P < 0.001). For treatment seeking, "External pressure" was a more common reason in urban patients (P < 0.001), who also had more psychiatric comorbidities (P = 0.026). Conclusion: Significant pattern differences exist between rural and urban substance dependents, warranting emphasis on locality-specific factors for appropriate intervention.

Short-term Clinical Outcome of Previously Untreated and Treated Schizophrenia and Impact of Duration of Untreated Psychosis.

Background: Duration of untreated psychosis (DUP) is an important modifiable factor affecting schizophrenia outcomes. A dearth of research in India on untreated versus treated schizophrenia warrants further research. Methods: This was a longitudinal study in a tertiary hospital over 2 years. Inpatients diagnosed with schizophrenia (N = 116), aged 18-45, were divided into untreated and treated groups. Diagnostic confirmation, severity assessment, and clinical outcome were done using ICD-10 criteria, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale. Follow-up was done at 12 and 24 weeks. DUP was measured, and its association with the outcome was assessed. Results: Final analysis included 100 patients, 50 each of previously untreated and treated. Untreated patients had lower age and duration of illness (DOI), but higher DUP (p < .001). Treated patients showed much improvement on CGI-I at 12 weeks (p = .029), with no difference at 24 weeks. PANSS severity comparison showed no difference, and both groups followed a declining trend. In untreated patients, age of onset (AoO) was negatively correlated with severity (except general symptoms at baseline) at all follow-ups ('r' range = -0.32 to -0.49, p < .05), while DOI showed a positive correlation with negative and general symptoms at 12 weeks (r ~ 0.3, p < .05). Treated patients showed inconsistent and lower negative correlation between AoO and PANSS, with no correlation between severity and DOI. The mean sample DUP was 17.9 ± 31.6 weeks; it negatively correlated with education (r = -0.25, p = .01) and positively with PANSS severity ('r' range = 0.22 to 0.30, p < .05) at all follow-ups, especially negative symptoms. Patients with no or minimal improvement on CGI at 24 weeks had higher DUP (Quade's ANOVA F[1,98] = 6.24, p = .014). Conclusion: Illness variables in untreated schizophrenia affect severity, which has delayed improvement than treated schizophrenia. Higher DUP is associated with negative symptoms of schizophrenia.

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler.

Fun30 is the prototype of the Fun30-SMARCAD1-ETL subfamily of nucleosome remodelers involved in DNA repair and gene silencing. These proteins appear to act as single-subunit nucleosome remodelers, but their molecular mechanisms are, at this point, poorly understood. Using multiple sequence alignment and structure prediction, we identify an evolutionarily conserved domain that is modeled to contain a SAM-like fold with one long, protruding helix, which we term SAM-key. Deletion of the SAM-key within budding yeast Fun30 leads to a defect in DNA repair and gene silencing similar to that of the fun30Δ mutant. In vitro, Fun30 protein lacking the SAM-key is able to bind nucleosomes but is deficient in DNA-stimulated ATPase activity and nucleosome sliding and eviction. A structural model based on AlphaFold2 prediction and verified by crosslinking-MS indicates an interaction of the long SAM-key helix with protrusion I, a subdomain located between the two ATPase lobes that is critical for control of enzymatic activity. Mutation of the interaction interface phenocopies the domain deletion with a lack of DNA-stimulated ATPase activation and a nucleosome-remodeling defect, thereby confirming a role of the SAM-key helix in regulating ATPase activity. Our data thereby demonstrate a central role of the SAM-key domain in mediating the activation of Fun30 catalytic activity, thus highlighting the importance of allosteric activation for this class of enzymes.

Establishment and function of chromatin organization at replication origins.

The origin recognition complex (ORC) is essential for initiation of eukaryotic chromosome replication as it loads the replicative helicase-the minichromosome maintenance (MCM) complex-at replication origins1. Replication origins display a stereotypic nucleosome organization with nucleosome depletion at ORC-binding sites and flanking arrays of regularly spaced nucleosomes2-4. However, how this nucleosome organization is established and whether this organization is required for replication remain unknown. Here, using genome-scale biochemical reconstitution with approximately 300 replication origins, we screened 17 purified chromatin factors from budding yeast and found that the ORC established nucleosome depletion over replication origins and flanking nucleosome arrays by orchestrating the chromatin remodellers INO80, ISW1a, ISW2 and Chd1. The functional importance of the nucleosome-organizing activity of the ORC was demonstrated by orc1 mutations that maintained classical MCM-loader activity but abrogated the array-generation activity of ORC. These mutations impaired replication through chromatin in vitro and were lethal in vivo. Our results establish that ORC, in addition to its canonical role as the MCM loader, has a second crucial function as a master regulator of nucleosome organization at the replication origin, a crucial prerequisite for efficient chromosome replication.

Multistage Ion Mobility Spectrometry Combined with Infrared Spectroscopy for Glycan Analysis.

The structural complexity of glycans makes their characterization challenging, not only because of the presence of various isomeric forms of the precursor molecule but also because the fragments can themselves be isomeric. We have recently developed an IMS-CID-IMS approach using structures for lossless ion manipulations (SLIM) combined with cryogenic infrared (IR) spectroscopy for glycan analysis. It allows mobility separation and collision-induced dissociation of a precursor glycan followed by mobility separation and IR spectroscopy of the fragments. While this approach holds great promise for glycan analysis, we often encounter fragments for which we have no standards to identify their spectroscopic fingerprint. In this work, we perform proof-of-principle experiments employing a multistage SLIM-based IMS-CID technique to generate second-generation fragments, followed by their mobility separation and spectroscopic interrogation. This approach provides detailed structural information about the first-generation fragments, including their anomeric form, which in turn can be used to identify the precursor glycan.

Comparison between Air Q and intubating laryngeal mask airway as intubation conduits in patients with simulated fixed cervical spine: a prospective observational study.

The intubating laryngeal mask airway (ILMA) can be used for ventilation and oxygenation between intubation attempts, but there is a varied success rate ranging from 33% to 96%. Air Q is a relatively new entrant. Parker flex tube aids in atraumatic intubation. The primary aim of this study was to compare Air Q intubating laryngeal airway with ILMA as intubation conduits in patients with simulated fixed cervical spine using a Parker flex tube. It was a single-blinded, randomized, prospective, and comparative study conducted on 91 patients aged between 18 to 60 years of either sex, scheduled to undergo elective surgery under general anesthesia belonging to the American Society of Anesthesiologists physical status I and II. Out of 45 patients in each group, Air Q was successfully placed in 43 patients and ILMA was successfully placed in 44 patients. 35.56% of the patients required maneuvers for placing the Air Q, whereas, for placing the ILMA, only 15.56% of the patients required maneuvers. Intubation through the AIR Q was successful in 39 patients and through the ILMA in 44 patients, but there was no significant difference between the two groups. The number of attempts and the time of device insertion were comparable. There were a similar number of attempts, maneuvers required, and time is taken for endotracheal intubation. The incidence of cough and sore throat was comparable in both groups. We conclude that ILMA has a higher success rate than Air Q for tracheal intubation with Parker Flex tube in patients with simulated fixed cervical spine. More optimized maneuvers were required for the placement of Air Q.

Drug Utilization Research and Predictors of Outcomes in the Intensive Care Unit of a Tertiary Care Hospital: A Prospective Observational Study.

BACKGROUND: Multiple drugs are commonly prescribed to intensive care unit (ICU) patients owing to the disease profile, multiple organ dysfunction, prophylaxis, management of stress ulcers, nosocomial infections, etc. This study aimed to evaluate the drug utilization patterns and factors influencing mortality and duration of stay in ICU patients.  Methodology: A prospective observational study was conducted in the ICU of our tertiary care hospital, Postgraduate Institute of Medical Sciences, Rohtak. Data was collected from treatment charts of patients using a structured pretested proforma. World Health Organization Anatomical Therapeutic Chemical/Defined Daily Dose (WHO ATC/DDD) methodology and core prescribing indicators were used to assess drug utilization data. The effect of different variables on mortality and duration of stay in the ICU was evaluated using regression analysis. RESULTS: An average of 8.78 drugs were prescribed per patient. Among the 922 prescriptions, anti-infectives, anti-inflammatory drugs, and drugs acting on the gastrointestinal tract were the most frequent medication classes prescribed. Polypharmacy and trade name prescribing were common. For most of the drugs, the prescribed daily dose corresponded to the WHO-DDD except ceftriaxone and levofloxacin. Age, presence of cardiac disorders, and Glasgow Coma Scale (GCS) score at admission directly correlated with mortality while the use of diuretics had a negative correlation with the duration of ICU stay.  Conclusions: There is a need to rationalize drug therapy in the ICU with regard to limiting polypharmacy and emphasizing generic drug name prescribing and adherence to the essential drug list. Antibiotic prescription patterns, in particular, deserve a special focus keeping in mind the multitude of factors demanding aggressive antibiotic use in critically ill intensive care patients.

A VPS15-like kinase regulates apicoplast biogenesis and autophagy by promoting PI3P generation in Toxoplasma gondii.

Phosphoinositides are important second messengers that regulate key cellular processes in eukaryotes. While it is known that a single phosphoinositol-3 kinase (PI3K) catalyses the formation of 3'-phosphorylated phosphoinositides (PIPs) in apicomplexan parasites like Plasmodium and Toxoplasma, how its activity and PI3P formation is regulated has remained unknown. Present studies involving a unique Vps15 like protein (TgVPS15) in Toxoplasma gondii provides insight into the regulation of phosphatidyl-3-phosphate (PI3P) generation and unravels a novel pathway that regulates parasite development. Detailed investigations suggested that TgVPS15 regulates PI3P formation in Toxoplasma gondii, which is important for the inheritance of the apicoplast-a plastid like organelle present in most apicomplexans and parasite replication. Interestingly, TgVPS15 also regulates autophagy in T. gondii under nutrient-limiting conditions as it promotes autophagosome formation. For both these processes, TgVPS15 uses PI3P-binding protein TgATG18 and regulates trafficking and conjugation of TgATG8 to the apicoplast and autophagosomes, which is important for biogenesis of these organelles. TgVPS15 has a protein kinase domain but lacks several key residues conserved in conventional protein kinases. Interestingly, two critical residues in its active site are important for PI3P formation and parasitic functions of this kinase. Collectively, these studies unravel a signalling cascade involving TgVPS15, a novel effector of PI3-kinase in T. gondii and possibly other Apicomplexa, that regulate critical processes like apicoplast biogenesis and autophagy.

Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway.

Objectives: Excess intake of a high-fatty diet (HFD) together with zymosan administration mediates vasculitis response which leads to impaired serum lipid levels and causes arterial stiffness. In the development of new cholesterol-lowering medications, PCSK9 inhibitor (proprotein convertase subtilisin/kexin type 9) is an emerging therapeutic. The goal of the present study was to see whether anti-PCSK9 mAb1 might prevent vasculitis in C57BL/6 mice by blocking TLR2/NF-B activation in HFD and Zymosan-induced vasculitis. Materials and Methods: Protein-protein molecular docking was performed to validate the binding affinity of anti-PCSK9 mAb1 against TLR2. Under the experimental study, mice were randomly allocated to the following groups: Group I: standard mice diet (30 days) + Zymosan vehicle (sterile PBS solution of 5mg/ml on 8th day); Group II: HFD (30 days) + Zymosan ( single IP dose 80 mg/kg on day 8th); Group III: HFD+Zymosan + anti-PCSK9 mAb1 (6 mg/kg, s.c. on 10th and 20th days); Group IV: HFD+Zymosan+anti-PCSK9 mAb1 (10 mg/kg, s.c. on 10th and 20th days). Results: In comparison with the low dose of anti-PCSK9 mAb1 (6 mg/kg), the high dose of anti-PCSK9 mAb1 (10 mg/kg) together with HFD and Zymosan inhibited vasculitis more effectively by decreasing aortic TLR2 and NF-B levels, reducing serum TNF- and IL-6, and up-regulating liver LDLR levels, which down-regulated serum LDL-C and improved serum lipids levels. Histopathological studies showed that anti-PCSK9 mAb1 treatment reduced plaque accumulation in the aorta of mice. Conclusion: These findings indicate that anti-PCSK9 mAb1 has therapeutic potential in reducing HFD and Zymosan-induced vascular inflammation.

Identification of Mobility-Resolved N-Glycan Isomers.

Glycan analysis has evolved considerably during the last decade. The advent of high-resolution ion-mobility spectrometry has enabled the separation of isomers with only the slightest of structural differences. However, the ability to separate such species raises the problem of identifying all the mobility-resolved peaks that are observed, especially when analytical standards are not available. In this work, we report an approach based on the combination of IMSn with cryogenic vibrational spectroscopy to identify N-glycan reducing-end anomers. By identifying the reducing-end α and ß anomers of diacetyl-chitobiose, which is a disaccharide that forms part of the common core of all N-glycans, we are able to assign mobility peaks to reducing anomers of a selection of N-glycans of different sizes, starting from trisaccharides such as Man-1 up to glycans containing nine monosaccharide units, such as G2. By building an infrared fingerprint database of the identified N-glycans, our approach allows unambiguous identification of mobility peaks corresponding to reducing-end anomers and distinguishes them from positional isomers that might be present in a complex mixture.

Prevalence of micronutrient deficiency and its impact on the outcome of childhood cancer: A prospective cohort study.

BACKGROUND & AIMS: Impact of micronutrient deficiency on childhood malignancy is unexplored. We estimated the prevalence of baseline micronutrient deficiency in children with cancer and its impact on event-free survival (EFS) and overall survival (OS). METHODS: A longitudinal cohort study was conducted at a tertiary cancer centre in India. Children (≤18 years) with de novo malignancy were enrolled between October 2012 and May 2014. Baseline levels of vitamin B12, folate, zinc, selenium, copper, and iron were measured and values below 150 pmol/L, 6 ng/mL, International Zinc Nutrition Collaborative Group cut-off, 0.5 µmol/L, 10 µmol/L, and 50 µg/dL, respectively, indicated deficiency. RESULTS: Total 535 children [326 (60.9%) haematological and 209 (39.1%) solid malignancies] were enrolled with median follow-up of 66 months. Vitamin B12, folate, zinc, selenium, copper and iron deficiencies were found in 209 (39.1%), 89 (16.6%), 173 (32.3%), 39 (7.3%), 12 (2.2%), and 231 (43.2%) children, respectively. Selenium deficiency independently predicted poor EFS (hazard ratio [HR] = 1.56; p = 0.038) and OS (HR = 1.65; p = 0.027) in the cohort. In haematological malignancies, selenium deficiency predicted poor EFS (HR = 1.81; p = 0.023) and OS (HR = 2.12; p = 0.004). In solid malignancies, vitamin B12 (HR = 1.55; p = 0.028) and zinc (HR = 1.74; p = 0.009) deficiencies predicted poor EFS, and zinc deficiency predicted poor OS (HR = 1.77; p = 0.009). Multiple micronutrient (≥3) deficiencies also predicted poor EFS (HR = 1.69; p = 0.001) and OS (HR = 1.83; p < 0.001) in the whole cohort. CONCLUSIONS: Selenium deficiency was independently predictive of adverse outcomes in childhood cancer, particularly in haematological malignancies. Zinc deficiency adversely affected solid tumours. The adjunct use of micronutrient supplementation in paediatric malignancies should be explored.

A New Strategy Coupling Ion-Mobility-Selective CID and Cryogenic IR Spectroscopy to Identify Glycan Anomers.

Determining the primary structure of glycans remains challenging due to their isomeric complexity. While high-resolution ion mobility spectrometry (IMS) has recently allowed distinguishing between many glycan isomers, the arrival-time distributions (ATDs) frequently exhibit multiple peaks, which can arise from positional isomers, reducing-end anomers, or different conformations. Here, we present the combination of ultrahigh-resolution ion mobility, collision-induced dissociation (CID), and cryogenic infrared (IR) spectroscopy as a systematic method to identify reducing-end anomers of glycans. Previous studies have suggested that high-resolution ion mobility of sodiated glycans is able to separate the two reducing-end anomers. In this case, Y-fragments generated from mobility-separated precursor species should also contain a single anomer at their reducing end. We confirm that this is the case by comparing the IR spectra of selected Y-fragments to those of anomerically pure mono- and disaccharides, allowing the assignment of the mobility-separated precursor and its IR spectrum to a single reducing-end anomer. The anomerically pure precursor glycans can henceforth be rapidly identified on the basis of their IR spectrum alone, allowing them to be distinguished from other isomeric forms.

Yta7, a chromatin segregase regulated by the cell cycle machinery.

We have recently revealed the existence of a cell cycle-regulated chromatin segregase, Yta7 (Yeast Tat-binding Analog 7), involved in chromosome replication. Phosphorylation of Yta7 by S-CDK (S-phase Cyclin-Dependent Kinase) regulates its function. These findings link the cell cycle to chromatin biology and suggest how chromatin-modifying enzymes become S phase-specific.

Identification of N-glycan positional isomers by combining IMS and vibrational fingerprinting of structurally determinant CID fragments.

While glycans are present on the surface of cells in all living organisms and play key roles in most biological processes, their isomeric complexity makes their structural characterization challenging. Of particular importance are positional isomers, for which analytical standards are difficult to obtain. We combine ultrahigh-resolution ion-mobility spectrometry with collision-induced dissociation and cryogenic infrared spectroscopy to determine the structure of N-glycan positional isomers. This approach is based on first separating the parent molecules by SLIM-based IMS, producing diagnostic fragments specific to each positional isomer, separating the fragments by IMS, and identifying them by comparing their IR fingerprints to a previously recorded spectral database. We demonstrate this strategy using a bottom-up scheme to identify the positional isomers of the N-linked glycan G0-N, in which a terminal N-acetylglucosamine (GlcNAc) is attached to either the α-3 or α-6 branch of the common N-glycan pentasaccharide core. We then use IR fingerprints of these newly identified isomers to identify the positional isomers of G1 and G1F, which are biantennary complex-type N-glycans with a terminal galactose attached to either the α-3 or α-6 branch, and in the case of G1F a fucose attached to the reducing-end GlcNAc. Starting with just a few analytical standards, this fragment-based spectroscopy method allows us to develop a database which we can use to identify positional isomers. The generalization of this approach would greatly facilitate glycan analysis.

PI4-kinase and PfCDPK7 signaling regulate phospholipid biosynthesis in Plasmodium falciparum.

PfCDPK7 is an atypical member of the calcium-dependent protein kinase (CDPK) family and is crucial for the development of Plasmodium falciparum. However, the mechanisms whereby PfCDPK7 regulates parasite development remain unknown. Here, we perform quantitative phosphoproteomics and phospholipid analysis and find that PfCDPK7 promotes phosphatidylcholine (PC) synthesis by regulating two key enzymes involved in PC synthesis, phosphoethanolamine-N-methyltransferase (PMT) and ethanolamine kinase (EK). In the absence of PfCDPK7, both enzymes are hypophosphorylated and PMT is degraded. We further find that PfCDPK7 interacts with 4'-phosphorylated phosphoinositides (PIPs) generated by PI4-kinase. Inhibition of PI4K activity disrupts the vesicular localization PfCDPK7. P. falciparum PI4-kinase, PfPI4K is a prominent drug target and one of its inhibitors, MMV39048, has reached Phase I clinical trials. Using this inhibitor, we demonstrate that PfPI4K controls phospholipid biosynthesis and may act in part by regulating PfCDPK7 localization and activity. These studies not only unravel a signaling pathway involving PfPI4K/4'-PIPs and PfCDPK7 but also provide novel insights into the mechanism of action of a promising series of candidate anti-malarial drugs.

Global Hunger Index does not really measure hunger - An Indian perspective.

The Global Hunger Index (GHI) is calculated and disseminated annually. India, which is the 5th largest economy in the world and has a good ranking in many other indicators, has a poor ranking based on this index. After a critical review of the appropriateness of the indicators used in GHI, the Indian Council of Medical Research has the viewpoint that the indicators of undernourishment, stunting, wasting and child mortality do not measure hunger per se. Referring to this index as a Hunger Index, and thereby ranking countries is not appropriate, since many of the measures that are used to evolve an index that measures hunger are probably contextual. Countries should therefore evolve their own measures that are suitable for their own context.