O6-Alkylguanine-DNA Alkyltransferase Maintains Genome Integrity by Forming DNA-Protein Cross-Links during Inflammation-Associated Peroxynitrite-Mediated DNA Damage.

Inflammation is an early immune response against invading pathogens and damaged tissue. Although beneficial, uncontrolled inflammation leads to various diseases including cancer in a chronic setting. Peroxynitrite (PN) is a major reactive nitrogen species generated during inflammation. It produces various DNA lesions including 8-nitro-guanine which spontaneously converts into abasic sites, resulting in DNA strand breakage, and is suspected to be mutagenic. Here, we report the discovery of a previously unrecognized function of the human repair protein O6-alkylguanine-DNA alkyltransferase (hAGT or MGMT). We showed that hAGT through its active site nucleophilic Cys145 thiolate spontaneously reacts with 8-nitro-guanine in DNA to form a stable DNA-protein cross-link (DPC). Interestingly, the process of DPC formation provided protection from PN-mediated genome instability, growth arrest, and apoptosis. The Cys145 mutant of hAGT failed to form a DPC and was unable to protect cells from inflammation-associated PN-mediated cytotoxicity. Gel-shift, dot blot, and UV-vis assays showed formation of a covalent linkage between PN-damaged DNA and hAGT through its active site Cys145. Finally, expression of hAGT was found to be significantly increased by induced macrophages and PN. The data presented here clearly demonstrated hAGT as a dual-function protein that along with DNA repair is capable of maintaining genomic integrity and providing protection from the toxicity caused by PN-mediated DNA damage. Although DPCs are known to be detrimental to the cell, recently, multiple pathways have been identified in normal cells for their repair.

Impact on Emergency Department Interventions After Implementing a Guideline Based on the Pediatric Emergency Care Applied Research Network Prediction Rule for Identifying Low-Risk Febrile Infants 29 to 60 Days Old.

BACKGROUND: The Pediatric Emergency Care Applied Research Network (PECARN) prediction rule identifies febrile infants at low risk for serious bacterial infection (SBI). However, its impact on avoidable interventions in the emergency department remains unknown. OBJECTIVE: To study the impact on lumbar puncture (LP) performance, empiric antibiotic use, and admissions after implementing a febrile infant clinical practice guideline for infants aged 29 to 60 days based on the PECARN prediction rule in the pediatric emergency department. METHODS: This single center preintervention to postintervention study included infants 29 to 60 days old who presented with a chief complaint of fever from November 2018 to November 2021 and were assessed for SBI via blood culture and either urinalysis or urine culture. A new clinical practice guideline based on the PECARN prediction rule was implemented on December 2019. Lumbar puncture attempts, antibiotic administration, and admissions were compared preimplementation and postimplementation and in subgroups of low- and high-risk patients. RESULTS: Of 1597 (PRE: 785, POST: 812) infants presenting with fever, 1032 (PRE: 500, POST: 532) met inclusion criteria. Adoption of guideline recommendations (measured as procalcitonin order rate) was 89.7% in eligible infants postimplementation. Overall, there was a significant decrease in LPs (PRE: 30.6%, POST: 22.6%, P < 0.05) and no significant change in antibiotics or admissions. Among low-risk infants, there was a significant reduction in LPs (PRE: 17.2%, POST: 4.4%, P < 0.05) and antibiotics (PRE: 14.5%, POST: 4.1%; P < 0.05). There was no change in missed SBI (PRE: 3, POST: 2, P = 0.65). No cases of missed meningitis preimplementation or postimplementation were observed. CONCLUSIONS: After implementation of a guideline based on the PECARN prediction rule, we observed a reduction of LPs and antibiotics in low-risk infants. Overall, a decrease in LPs was observed, whereas antibiotic use and admissions remained unchanged.

Bugs Behind the Bulging Eyeball: Microbiology and Antibiotic Management in Orbital Cellulitis With or Without Subperiosteal Abscess.

The objective of this study is to describe causative pathogens and current antibiotic management among hospitalized children with orbital cellulitis. This retrospective study, performed at a tertiary care children's health system, included patients up to 18 years old who presented with radiographic evidence of orbital cellulitis from 2012 to 2019. Of the 298 patients included in the study, 103 had surgery and an intraoperative culture obtained. A pathogen was recovered in 86 cultures (83.5%). The most common pathogens were Streptococcus anginosus group (26.2%), Streptococcus pyogenes (11.7%), methicillin-susceptible Staphylococcus aureus (10.7%), and Streptococcus pneumoniae (9.7%). Only 8/194 (4.1%) blood cultures returned positive. Median duration of intravenous antibiotics was 4 days and median total duration was 17 days. The most common empiric regimen prescribed was ceftriaxone and clindamycin (64.1%). Despite low incidence of methicillin-resistant S aureus, empiric antibiotics often consisted of 2 antibiotics to ensure coverage for this bacterium.

Improving the Accuracy of the Gynaecology Handover Process: An Effective Quality Improvement Project at a University Hospital in the United Kingdom.

Objectives The objective of this study was to introduce a new system of handover in the gynaecology department and ensure its effectiveness with dynamic improvement measures. This was launched as a quality improvement project in a district general hospital in the United Kingdom. The primary aim was to start and consolidate a new system of a separate gynaecology handover in the presence of consultants, registrars (incoming and outgoing), senior house officers (incoming and outgoing) and gynaecology nurses. Design The strategy for consolidation included a daily quality review on the basis of a fixed proforma, identifying the obstacles faced, and improvising dynamic solutions. A new quality check proforma was introduced which took into account: (i) Presence of team members, (ii) Following of proper SBAR (Situation, Background, Assessment, Recommendation) format in the handover, (iii) Updating of patients awaiting surgeries with every detail on the list, (iv) Proper handing over of pending referrals, (v) Mention of sick patients with proper importance, and (vi) Proper handing over of new admissions. A pilot study was done to evaluate the baseline performance of the unit regarding the gynaecology team handover on the basis of the same proforma. The result of the baseline study was noted as the reference. Each day the team receiving the handover was interviewed for the next five months about the quality of each of the parameters on the predesigned proforma and the responses were noted. The answers were designed in binary form (Yes/No). These results were compiled at the end of each month. The result from each individual month was reviewed and the problems were identified and practical solutions were applied. These changes were noted and plotted graphically as a bar diagram. The monthly audit results were tabulated in an Excel sheet (Microsoft Corporation, Redmond, Washington, United States). Results Pilot study results and final month results were compared with the help of the Mcnemar test and statistically significant improvement was noticed in seven out of eleven parameters. There was a steady and gradual improvement in the responses. The possible limitations of the study were also noted at the same time. Conclusion The quality improvement project was highly effective in improving the quality of handover and increased patient safety to a large extent.

Current Inpatient Screening Practices for Sexual History and STIs: An Opportunity to Seize.

The American Academy of Pediatrics recommends utilizing hospitalizations as an opportunity to provide sexual health screenings for adolescents. This study aimed to describe the current practice of sexual history documentation (SHxD) and sexually transmitted infection (STI) testing among adolescents admitted to a pediatric hospital medicine service. Retrospective cross-sectional study of adolescents (14-19 years old) admitted to the PHM service from 2017-2019 was performed at an academic children's health system. Patient (demographics, history of complex chronic condition, and insurance), hospitalization (length of stay, diagnosis, STI tests ordered/results), and physician (level of training and gender) characteristics were extracted for each encounter. A natural language processing algorithm identified the presence of SHxD. Univariate analysis and multivariable analysis were performed to detect factors associated with SHxD and STI screening. The prevalence of STIs was calculated for those who were tested. Out of 2242 encounters, SHxD and STI testing rates were 40.9% and 17.2%, respectively. Patient gender, race, lack of complex chronic condition, and resident involvement were predictive of SHxD and STI testing. SHxD increased the odds of STI testing significantly (OR 5.06, CI 3.90-6.58). Among those who were tested, the prevalence of STIs was highest for chlamydia (37/329, 11.2%). Overall, sexual health screening rates remain low in the hospital setting and future improvement initiatives are needed.

Inequalities for higher order differences of the logarithm of the overpartition function and a problem of Wang-Xie-Zhang.

Let p ¯ ( n ) denote the overpartition function. In this paper, our primary goal is to study the asymptotic behavior of the finite differences of the logarithm of the overpartition function, i.e., ( - 1 ) r - 1 Δ r log p ¯ ( n ) , by studying the inequality of the following form log ( 1 + C ( r ) n r - 1 / 2 - 1 + C 1 ( r ) n r ) < ( - 1 ) r - 1 Δ r log p ¯ ( n ) < log ( 1 + C ( r ) n r - 1 / 2 ) for n ≥ N ( r ) , where C ( r ) , C 1 ( r ) , and N ( r ) are computable constants depending on the positive integer r, determined explicitly. This solves a problem posed by Wang, Xie and Zhang in the context of searching for a better lower bound of ( - 1 ) r - 1 Δ r log p ¯ ( n ) than 0. By settling the problem, we are able to show that lim n → ∞ ( - 1 ) r - 1 Δ r log p ¯ ( n ) = π 2 ( 1 2 ) r - 1 n 1 2 - r . .

Log-convexity and the overpartition function.

Let p ¯ ( n ) denote the overpartition function. In this paper, we obtain an inequality for the sequence Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 which states that log ( 1 + 3 π 4 n 5 / 2 - 11 + 5 α n 11 / 4 ) < Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 < log ( 1 + 3 π 4 n 5 / 2 ) for n ≥ N ( α ) , where α is a non-negative real number, N ( α ) is a positive integer depending on α , and Δ is the difference operator with respect to n. This inequality consequently implies log -convexity of { p ¯ ( n ) / n n } n ≥ 19 and { p ¯ ( n ) n } n ≥ 4 . Moreover, it also establishes the asymptotic growth of Δ 2 log p ¯ ( n - 1 ) / ( n - 1 ) α n - 1 by showing lim n → ∞ Δ 2 log p ¯ ( n ) / n α n = 3 π 4 n 5 / 2 .

Development and validation of a new antenatal warning score system (DRRiP) for neonatal complications of gestational diabetes.

OBJECTIVE: To evaluate the DRRiP (Diabetes Related Risk in Pregnancy) score warning system as a tool for predicting neonatal morbidity in gestational diabetes. METHODS: A retrospective observational cohort study. By applying nine parameters from an antenatal trichotomy of glycemic, ultrasound, and clinical characteristics, DRRiP scores were calculated and assigned to each patient using a checklist tool. Logistic regression models were used to evaluate the association between DRRiP score and adverse fetal outcomes, after adjusting for maternal age and body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: In all, 627 women were studied. DRRiP score was an excellent predictor of macrosomia and shoulder dystocia (both areas under the receiver operating characteristics curves [AUROC] = 0.86), and a modest predictor of preterm delivery, hyperbilirubinemia, neonatal intensive care unit admission and a composite of either of the studied events (AUROC range 0.63-0.69). For the composite outcome, the sensitivity of an amber trigger score of 1 was 68.7% (95% confidence interval [CI] 62.27%-74.63%) and specificity was 48.87% (95% CI 43.85%-53.9%). Specificity at a red trigger score of 3 (89.7%) and a graded increase in post-test probability (90.7% risk at a score of 5) were highly encouraging. CONCLUSION: DRRiP score offers reasonable discriminative performance that could be clinically useful for meaningful risk stratification when making delivery plans.

A method to advance adolescent sexual health research: Automated algorithm finds sexual history documentation.

Background: We aimed to develop and validate a rule-based Natural Language Processing (NLP) algorithm to detect sexual history documentation and its five key components [partners, practices, past history of sexually transmitted infections (STIs), protection from STIs, and prevention of pregnancy] among adolescent encounters in the pediatric emergency and inpatient settings. Methods: We iteratively designed a NLP algorithm using pediatric emergency department (ED) provider notes from adolescent ED visits with specific abdominal or genitourinary (GU) chief complaints. The algorithm is composed of regular expressions identifying commonly used phrases in sexual history documentation. We validated this algorithm with inpatient admission notes for adolescents. We calculated the sensitivity, specificity, negative predictive value, positive predictive value, and F1 score of the tool in each environment using manual chart review as the gold standard. Results: In the ED test cohort with abdominal or GU complaints, 97/179 (54%) provider notes had a sexual history documented, and the NLP algorithm correctly classified each note. In the inpatient validation cohort, 97/321 (30%) admission notes included a sexual history, and the NLP algorithm had 100% sensitivity and 98.2% specificity. The algorithm demonstrated >97% sensitivity and specificity in both settings for detection of elements of a high quality sexual history including protection used and contraception. Type of sexual practice and STI testing offered were also detected with >97% sensitivity and specificity in the ED test cohort with slightly lower performance in the inpatient validation cohort. Conclusion: This NLP algorithm automatically detects the presence of sexual history documentation and its key components in ED and inpatient settings.

Chemotherapy vs. Immunotherapy in combating nCOVID19: An update.

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis.

Isolated Fallopian Tube Torsion: A Rare Entity.

Isolated fallopian tube torsion is an extremely rare occurrence in a young female. The lady concerned presented with acute abdominal pain and the ovaries were normal on the scan with dilated fallopian tubes. On laparoscopy, it was revealed that she was suffering from fallopian tube torsion and laparoscopic salpingectomy was performed. The patient recovered well postoperatively.

Determining Normative Values for Cerebrospinal Fluid Profiles in Infants.

BACKGROUND: Previous studies of reference values for cerebrospinal fluid (CSF) profiles have been limited by small sample size and few exclusion criteria. OBJECTIVE: To determine age-specific normative CSF white blood cell count (WBC), glucose, and protein values in infants ≤90 days old. METHODS: Performed a retrospective cross-sectional study of infants ≤90 days old who had a diagnostic lumbar puncture between 2008 and 2016. Infants with bacterial meningitis, bacteremia, UTI, positive CSF herpes simplex virus polymerase chain reaction (PCR) result, traumatic lumbar puncture, ventriculoperitoneal shunt, prematurity, recent seizure, previous antibiotic use, and history of a complex chronic condition were excluded for calculations to determine normative values. Data on demographics and CSF values (WBC with differential, protein, glucose, enterovirus PCR) were collected. CSF values were compared by age and by enterovirus PCR results using Kruskal-Wallis and Wilcoxon rank tests. RESULTS: A total of 1029 out of 2000 patients were included and divided into 3 age groups: 0 to 28 days, 29 to 60 days, 61 to 90 days. CSF WBC values were significantly greater for 0- to 28-day old infants (median: 3, 95th percentile: 14) than for 29- to 60-day and 61- to 90-day old infants (median: 2 and 2; 95th percentile: 7 and 11, respectively) (P < .001). With each month of life, the median CSF protein significantly decreased and glucose significantly increased. In the CSF WBC differential, monocytes were found to be prevalent. CONCLUSION: We determined age-specific normative components for CSF profile values for infants 0 to 90 days.

Enzyme mediated resistant starch production from Indian Fox Nut (Euryale ferox) and studies on digestibility and functional properties.

Starch rich foods are almost indispensable in mundane diet of people round the globe. Rapid digestibility of starch culminates into elevated blood glucose level which is an evident factor for many diseases. To curb this rapid digestibility and the elevated glycemic response, resistant starch content in highly nutritious but unexplored popped makhana (Euryale ferox) was increased by amylopullulanase treatment. In the present study, amylopullulanase treated makhana flour (MM) was compared with the native makhana flour (NM) based on physicochemical and functional properties, where enhanced amylose content, resistant starch and crystallinity were recorded to be 12.33 %, 14.88 % and 11.32 % respectively, whereas, readily digestible starch and oil holding capacity decreased by 13.01 % and 3.12 g/g respectively. The present study ensures the reduction and sustainable release of glucose during in vitro digestibility analysis. These findings point out the elevated potential of amylopullulanase treated makhana flour for therapeutic food formulation.

The neurotoxic MEC-4(d) DEG/ENaC sodium channel conducts calcium: implications for necrosis initiation.

Hyperactivation of the Caenorhabditis elegans MEC-4 Na(+) channel of the DEG/ENaC superfamily (MEC-4(d)) induces neuronal necrosis through an increase in intracellular Ca(2+) and calpain activation. How exacerbated Na(+) channel activity elicits a toxic rise in cytoplasmic Ca(2+), however, has remained unclear. We tested the hypothesis that MEC-4(d)-induced membrane depolarization activates voltage-gated Ca(2+) channels (VGCCs) to initiate a toxic Ca(2+) influx, and ruled out a critical requirement for VGCCs. Instead, we found that MEC-4(d) itself conducts Ca(2+) both when heterologously expressed in Xenopus oocytes and in vivo in C. elegans touch neurons. Data generated using the Ca(2+) sensor cameleon suggest that an induced release of endoplasmic reticulum (ER) Ca(2+) is crucial for progression through necrosis. We propose a refined molecular model of necrosis initiation in which Ca(2+) influx through the MEC-4(d) channel activates Ca(2+)-induced Ca(2+) release from the ER to promote neuronal death, a mechanism that may apply to neurotoxicity associated with activation of the ASIC1a channel in mammalian ischemia.

A porous porphyrin organic polymer (PPOP) for visible light triggered hydrogen production.

A visible light active porphyrin-based porous organic polymer having high chemical stability and surface area has been synthesized and its ability to influence the photocatalytic activity of large band gap-TiO2 nanoparticles has been tested. The resultant composite shows improved photocatalytic activity as compared to the parent precursors. This study provides insights into the photosensitizing ability of the polymer in addition to its ability to firmly harbor nanoparticles onto its surface.

Microbial transformation of tannin-rich substrate to gallic acid through co-culture method.

Modified solid-state fermentation (MSSF) of tannin-rich substrate yielding tannase and gallic acid was carried out using a co-culture of the filamentous fungi, Rhizopus oryzae (RO IIT RB-13, NRRL 21498) and Aspergillus foetidus (GMRB013 MTCC 3557). Powdered fruits of Terminalia chebula and powdered pod cover of Caesalpinia digyna was used in the process and the different process parameters for maximum production of tannase and gallic acid by co-culture method were optimized through media engineering. MSSF was carried out at the optimum conditions of 30 degrees C and 80% relative humidity. The optimal pH and incubation period was 5.0 and 48 h respectively. Through the co-culture technique the maximum yield of tannase and gallic acid was found to be 41.3 U/ml and 94.8% respectively.

Evolutionary operation-factorial design technique for optimization of conversion of mixed agroproducts into gallic acid.

This article presents the optimization of gallic acid production using filamentous fungi from tannin-rich mixed substrates taking into account the interaction effects of six variable process parameters. The methodology adopted for optimization was the evolutionary operation (EVOP)-factorial design technique. This technique combines the factorial method for designing experiments with the EVOP methodology for analyzing the experimental results systematically and arriving at conclusions according to its decision-making procedure. Standard deviation and error limits based on 95% confidence were calculated according to the relationship given in the literature. It was found that the best combinations of the process parameters at the optimum levels were 30 degrees C, 80% relative humidity, pH 5.0, 48-h incubation period, 3 mL of induced inoculum, and 35 g of mixed substrate, resulting in a gallic acid yield of 94.8% under modified solid-state fermentation.

Modulation of breathing behavior of layered coordination polymers via a solid solution approach: the influence of metal ions on sorption behavior.

Four iso-structural layered coordination polymers (CPs) of Cd(II) and Zn(II) were shown to exhibit breathing transitions with N2/H2 gases. Furthermore, the solid solutions containing Zn(II)/Cd(II) have shown better uptake capacities of gas than parent CPs. These results give some insights into the role of metal ions and anions for fine-tuning the porosity of CPs.

Post-synthetic modification of isomorphic coordination layers: exchange dynamics of metal ions in a single crystal to single crystal fashion.

A diverse set of guest molecules template the consistent formation of fifteen iso-structural layered structures containing a pyridine based tripodal ligand, divalent metal ions and anions. These materials have shown a remarkable ability to interconvert from Zn(II) to Cu(II), Cd(II) to Cu(II), Cu(II) to Cd(II) complexes in a SCSC (single crystal-to-single crystal) fashion.