Single-Atomic Co-N4 Sites with CrCo Nanoparticles for Metal-Air Battery-Driven Hydrogen Evolution.

Designing highly active and robust earth abundant trifunctional electrocatalysts for energy storage and conversion applications remain an enormous challenge. Herein, we report a trifunctional electrocatalyst (CrCo/CoN4@CNT-5), synthesized at low calcination temperature (550 °C), which consists of Co-N4 single atom and CrCo alloy nanoparticles and exhibits outstanding electrocatalytic performance for the hydrogen evolution reaction, oxygen evolution reaction, and oxygen reduction reaction. The catalyst is able to deliver a current density of 10 mA cm-2 in an alkaline electrolytic cell at a very low cell voltage of ∼1.60 V. When the catalyst is equipped in a liquid rechargeable Zn-air battery, it endowed a high open-circuit voltage with excellent cycling durability and outperformed the commercial Pt/C+IrO2 catalytic system. Furthermore, the Zn-air battery powered self-driven water splitting system is displayed using CrCo/CoN4@CNT-5 as sole trifunctional catalyst, delivering a high H2 evolution rate of 168 µmol h-1. Theoretical calculations reveal synergistic interaction between Co-N4 active sites and CrCo nanoparticles, favoring the Gibbs free energy for H2 evolution. The presence of Cr not only enhances the H2O adsorption and dissociation but also tunes the electronic property of CrCo nanoparticles to provide optimized hydrogen binding capacity to Co-N4 sites, thus giving rise to accelerated H2 evolution kinetics. This work highlights the importance of the presence of small quantity of Cr in enhancing the electrocatalytic activity as well as robustness of single-atom catalyst and suggests the design of the multifunctional robust electrocatalysts for long-term H2 evolution application.

Landscaping tuberculosis multimorbidity: findings from a cross-sectional study in India.

BACKGROUND: Multimorbidity, the concurrent presence of two or more chronic conditions is an emerging public health challenge. Till date, most of the research have focused on the presence and interaction of selected co-morbidities in tuberculosis (TB). There exist a critical knowledge gap on the magnitude of multimorbidity among TB patients and its impact on health outcomes. METHODS: We undertook a cross-sectional study to assess the prevalence and patterns of multimorbidity among newly diagnosed TB patients in two states of India. A total of 323 patients were interviewed using a structured multimorbidity assessment questionnaire for primary care (MAQ-PC). MAQ-PC is already validated for Indian population and elicits 22 chronic conditions. We defined TB multimorbidity as the co-existence of TB with one or more chronic conditions and identified commonly occurring dyads (TB + single condition) and triads (TB + two conditions). RESULTS: More than half (52%) of TB patients reported multimorbidity. Among dyads, depression, diabetes mellitus (DM), acid peptic disease (APD), hypertension, chronic alcoholism, arthritis and chronic back ache (CBA) were the most common co-occurring conditions while 'DM + arthritis', 'depression + APD', 'depression + DM' were the most commonly occurring triads among TB patients. Factors such as increasing age, low levels of education, alcohol abusers, drug-resistant TB and having health insurance were significantly associated with multimorbidity among TB patients. CONCLUSIONS: Our findings suggest high prevalence of multimorbidity among newly diagnosed TB patients in India. The presence of concordant and discordant conditions with TB may increase the health complexity, thus necessitating appropriate care protocols. Given, the current situation, wherein TB and non-communicable diseases (NCD) services are delivered through collaborative framework between programmes, there is a need for addressing multimorbidity at the healthcare delivery level.

Anatomical and Functional Evaluation of Modified Abbe-McIndoe Vaginoplasty at a Tertiary Care Hospital.

BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome, the second important cause of primary amenorrhea, is characterized by complete mullerian agenesis in the presence of normal karyotype and normal functioning ovaries. Incidence is one in 4500 females. Treatment options include surgical and non-surgical methods. Surgical treatment by creating a neovagina between bladder and rectum is preferred as it gives immediate results. AIM: To evaluate the anatomical and functional outcomes of modified vaginoplasty procedures conducted in our institution. METHODS: An ambispective cohort study was conducted in the Department of Obstetrics and Gynaecology, at a tertiary care hospital and included 10 cases of MRKH syndrome, who underwent surgical treatment in our department. Postoperative outcome was noted. Sexual function was evaluated using the Female Sexual Function Index (FSFI) score. RESULTS: The mean duration of surgery was 40 minutes. The average blood loss during surgery in patients undergoing vaginoplasty was 60 ml. The mean length of the neovagina as measured 1 month after surgery was 7.9 cms. FSFI score was >30 in eight patients. Two patients were lost to follow-up. CONCLUSION: Modified McIndoe vaginoplasty is a simple, safe, and cost-effective procedure in the hands of experts. Only mature patients willing to follow the instructions and planning to get married soon should undergo this surgery.

Coupling Single-Ni-Atom with Ni-Co Alloy Nanoparticle for Synergistically Enhanced Oxygen Reduction Reaction.

Developing nonprecious metal-based oxygen reduction reaction (ORR) electrocatalysts with superior activity and durability is crucial for commercializing proton-exchange membrane (PEM) fuel cells. Herein, we report a metal-organic framework (MOF)-derived unique N-doped hollow carbon structure (NiCo/hNC), comprising of atomically dispersed single-Ni-atom (NiN4) and small NiCo alloy nanoparticles (NPs), for highly efficient and durable ORR catalysis in both alkaline and acidic electrolytes. Density functional theory (DFT) calculations reveal the strong coupling between NiN4 and NiCo NPs, favoring the direct 4e- transfer ORR process by lengthening the adsorbed O-O bond. Moreover, NiCo/hNC as a cathode electrode in PEM fuel cells delivered a stable performance. Our findings not only furnish the fundamental understanding of the structure-activity relationship but also shed light on designing advanced ORR catalysts.

Introducing Clinical Pathology Course to Fourth Year Medical Students as a Bridge between Pre-clinical and Clinical Medical Sciences.

There isn't any vertical integration of pre-clinical and clinical sciences subjects in the existing Kathmandu University MBBS curriculum. Many of the graduates are not able to correlate the clinico-pathological aspects of various diseases as a result the rational use of investigations for diagnosing various diseases is compromised. There are few published examples of implementation of pathology instruction courses during the clinical years of medical training but it is not universally practiced. This lack of exposure to pathology may lead to poor understanding of laboratory testing and the role of pathologists in patient care. To set and implement an exemplary vertical integration of pre-clinical science with clinical science. A 12 credit hours clinical pathology education course comprising clinical hematology, cytopathology and histopathology was developed. Students belonging from the ongoing fourth year MBBS course of Birat Medical College were enrolled in the course. All of the interactive lecture sessions were delivered via an e-learning interface, using the Zoom platform as the main teaching methods. Evaluation of students' achievement of learning objectives was conducted through distributing pre and post-test online multiple-choice questionnaires. Chi-square tests were used to compare the variables between pre-test and post-test questionnaire responses. Results suggested that the designed clinical pathology course is valuable. The pretest and post-test questionnaire responses revealed the positive impact regarding the importance of introducing clinical pathology courses within the clinical year of MBBS undergraduate curriculum. Response rate to the online session was 100%. The point of agreement between the pre-test and post-test questionnaire responses were highly achieved after intervention of the clinical pathology course. A statistically significant result (p < 0.05) between all of the pre-test and post-test questionnaire responses was noted. There was a strong positive recommendation for incorporating clinical laboratory medicine courses within the MBBS clinical science curriculum. The improvement observed among fourth-year MBBS students on learning the importance of clinical pathology courses was encouraging. This experience thus contributed to set and implement an exemplary vertical integration of pre-clinical science with clinical science.

ADRENAL HISTOPLASMOSIS: AN EASTERN INDIAN PERSPECTIVE.

Context: The clinical presentation of histoplasmosis is varied. Due to its propensity for adrenal involvement, histoplasmosis is an important differential diagnosis in any patient presenting with adrenal mass, bilateral in particular. Objective: Data on clinical presentation, pattern of adrenal involvement, radiological appearance and long-term follow-up of adrenal histoplasmosis are relatively sparse; hence we looked at it. Design: This record based single-centre retrospective study was conducted in one of the tertiary care hospitals, situated in eastern India catering the Gangetic delta. Subjects and methods: Data on demographic characters, presenting manifestations, biochemical & hormonal parameters and radiological appearance of confirmed adrenal histoplasmosis cases (n=9), admitted between 2015-2019 have been retrieved. The treatment outcome and condition of patients after 1-4 years of follow-up has also been discussed. Results: Four out of the nine (44.4%) patients had predisposing immunocompromised conditions in the form of diabetes and/or chronic alcoholism while rest were immunocompetent. Seven out of nine patients (77.8 %) had signs and symptoms suggestive of adrenal insufficiency, while two (22.2%) presented with only pyrexia of unknown origin. All of them had bilateral adrenal mass, though the radiologically appearances were different. All patients received anti-fungal agents with/without hydrocortisone and/or fludrocortisone. One patient died (11.1%), while majority responded favourably to treatment. Adrenocortical function did not recover completely. Conclusions: The possibility of adrenal histoplasmosis should always be considered in patients presenting with bilateral adrenal mass, irrespective of adrenal morphology. Treatment is effective, but many of them require supplemental hydrocortisone for quite a long period, if not lifelong. Mineralocorticoid deficiency, however, is not permanent.

Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Safety and efficacy of laparoscopic near-total colectomy and ileo-distal sigmoid anastomosis as a modification of total colectomy and ileorectal anastomosis for prophylactic surgery in patients with adenomatous polyposis syndromes: a comparative study.

AIM: Colectomy in patients with adenomatous polyposis (AP) syndromes demands good oncological and surgical outcome. Total colectomy with ileorectal anastomosis (TC-IRA) is one surgical option for these patients. Anastomotic leakage rates of 11% have been reported following TC-IRA. Ileo-distal sigmoid anastomosis (IDSA) is a recent modification of our practice. Our aim was to compare postoperative outcome in patients with AP following near-total colectomy with IDSA (NT-IDSA) and TC-IRA at a single institution. METHOD: A prospectively maintained database was reviewed to identify patients with AP who underwent laparoscopic NT-IDSA and TC-IRA. Patient demographics, early morbidity and mortality and outcome of endoscopic surveillance were evaluated. RESULTS: A total of 191 patients with AP underwent laparoscopic colectomy between 2006 and 2017, of whom 139 (72.8%) underwent TC-IRA and 52 (27.2%) NT-IDSA. The median age at surgery in the TC-IRA and NT-IDSA groups was 20 years (IQR 17-45) and 27 years (IQR 19-50), respectively. Grade II complications were comparable between the two groups. There were no anastomotic leakages in the NT-IDSA group compared with 15 (10.8%) in the TC-IRA group (P = 0.0125) and no reoperation in the NT-IDSA group compared with 17 (12.2%) in the TC-IRA group (P = 0.008). The frequency of polypectomies per flexible sigmoidoscopy was comparable between the two groups. CONCLUSION: This study demonstrates that laparoscopic NT-IDSA for polyposis is associated with a significant improvement in anastomotic leakage rates and surgical outcome. It is too soon to tell whether NT-IDSA alters the need for further intervention, either endoscopic polypectomy or further surgery.

Improving systems of care during and after a pregnancy complicated by hyperglycaemia: A protocol for a complex health systems intervention.

BACKGROUND: Many women with hyperglycaemia in pregnancy do not receive care during and after pregnancy according to standards recommended in international guidelines. The burden of hyperglycaemia in pregnancy falls disproportionately upon Indigenous peoples worldwide, including Aboriginal and Torres Strait Islander women in Australia. The remote and regional Australian context poses additional barriers to delivering healthcare, including high staff turnover and a socially disadvantaged population with a high prevalence of diabetes. METHODS: A complex health systems intervention to improve care for women during and after a pregnancy complicated by hyperglycaemia will be implemented in remote and regional Australia (the Northern Territory and Far North Queensland). The Theoretical Domains Framework was used during formative work with stakeholders to identify intervention components: (1) increasing workforce capacity, skills and knowledge and improving health literacy of health professionals and women; (2) improving access to healthcare through culturally and clinically appropriate pathways; (3) improving information management and communication; (4) enhancing policies and guidelines; (5) embedding use of a clinical register as a quality improvement tool. The intervention will be evaluated utilising the RE-AIM framework at two timepoints: firstly, a qualitative interim evaluation involving interviews with stakeholders (health professionals, champions and project implementers); and subsequently a mixed-methods final evaluation of outcomes and processes: interviews with stakeholders; survey of health professionals; an audit of electronic health records and clinical register; and a review of operational documents. Outcome measures include changes between pre- and post-intervention in: proportion of high risk women receiving recommended glucose screening in early pregnancy; diabetes-related birth outcomes; proportion of women receiving recommended postpartum care including glucose testing; health practitioner confidence in providing care, knowledge and use of relevant guidelines and referral pathways, and perception of care coordination and communication systems; changes to health systems including referral pathways and clinical guidelines. DISCUSSION: This study will provide insights into the impact of health systems changes in improving care for women with hyperglycaemia during and after pregnancy in a challenging setting. It will also provide detailed information on process measures in the implementation of such health system changes.

Utilization of LD slag from steel industry for the preparation of MF membrane.

This work is focused on utilizing the solid waste generated from steel industry for the fabrication of porous ceramic membrane from Linz Donawitz (LD) slag. Membranes were fabricated using uniaxial method sintered at three different temperatures like 650 °C, 850 °C and 950 °C. Membranes fabricated with raw LD slag gave a highly basic filtrate. In contrast with this issue, LD slag was modified using acetic acid and CO2 purging to convert calcium oxide which is present in the slag to calcium carbonate. The membranes fabricated from modified LD slag showed a filtrate pH of 8.4 and 8.5. Porosity, pore size distribution, flexural strength, chemical stability was determined and pure water flux experiments were conducted to evaluate the efficiency of the prepared membranes. Considering the raw materials cost, the cost of the fabricated membranes was estimated in the range of 32.55-55.7 USD/m2. This work gives a potential path to develop microfiltration ceramic membrane with, high porosity and great quality in terms of strength and chemical stability. The fabricated membranes were utilized in a hybrid technique (flocculation followed by microfiltration) for the treatment of cold roll mill (CRM) wastewater generated from steel industry. Use of LD slag for the fabrication of ceramic membrane is not only an appealing option towards the commercialization of membrane, yet also great option to reduce the solid waste which is dumped to the environment.

Porous and highly conducting cathode material PrBaCo2O6-δ: bulk and surface studies of synthesis anomalies.

The paradigm that chemical synthesis reduces the sintering temperature as compared to solid state synthesis seems to be violated in the case of the PrBaCo2O6-δ double perovskite. The sintering temperatures for pure phase samples synthesized through the solid state route (P-SSR) and the auto-combustion route (P-ACR) were found to be 1050 and 1150 °C, respectively. The porous microstructure of P-SSR is suitable for SOFC cathode materials while that of P-ACR is pore free. High-resolution transmission electron microscopy, Raman and scanning tunneling microscopy studies reveal that there is crystal growth on a smooth surface with a preferred orientation. Our results show that this anomalous synthesis behaviour is due to anisotropic surface nucleation growth. Thermodynamically, the higher decomposition temperature in the chemical route is due to stronger electron-phonon coupling and the higher value of change in entropy. The variation in the Co-O-Co bond angle reveals Jahn-Teller vibrational anisotropy in the-b plane leading to the anisotropic synthesis behaviour. This anisotropy is the reason for the violation of the paradigm.

Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease free at 5 years and relationship with low hormone receptor positivity.

BACKGROUND: We counsel our triple-negative breast cancer (TNBC) patients that the risk of recurrence is highest in the first 5 years after diagnosis. However, there are limited data with extended follow-up on the frequency, characteristics, and predictors of late events. METHODS: We queried the MD Anderson Breast Cancer Management System database to identify patients with stage I-III TNBC who were disease free at 5 years from diagnosis. The Kaplan-Meier method was used to estimate yearly recurrence-free interval (RFI), recurrence-free survival (RFS), and distant relapse-free survival (DRFS), as defined by the STEEP criteria. Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We identified 873 patients who were disease free at least 5 years from diagnosis with median follow-up of 8.3 years. The 10-year RFI was 97%, RFS 91%, and DRFS 92%; the 15-year RFI was 95%, RFS 83%, and DRFS 84%. On a subset of patients with oestrogen receptor and progesterone receptor percentage recorded, low hormone receptor positivity conferred higher risk of late events on multivariable analysis for RFS only (RFI: HR=1.98, 95% CI=0.70-5.62, P-value=0.200; RFS: HR=1.94, 95% CI=1.05-3.56, P-value=0.034; DRFS: HR=1.72, 95% CI=0.92-3.24, P-value=0.091). CONCLUSIONS: The TNBC survivors who have been disease free for 5 years have a low probability of experiencing recurrence over the subsequent 10 years. Patients with low hormone receptor-positive cancers may have a higher risk of late events as measured by RFS but not by RFI or DRFS.

Combined pathologic-genomic algorithm for early-stage breast cancer improves cost-effective use of the 21-gene recurrence score assay.

Background: The 21-gene recurrence score (RS) (Oncotype DX®; Genomic Health, Redwood City, CA) partitions hormone receptor positive, node negative breast cancers into three risk groups for recurrence. The Anne Arundel Medical Center (AAMC) model has previously been shown to accurately predict RS risk categories using standard pathology data. A pathologic-genomic (P-G) algorithm then is presented using the AAMC model and reserving the RS assay only for AAMC intermediate-risk patients. Patients and methods: A survival analysis was done using a prospectively collected institutional database of newly diagnosed invasive breast cancers that underwent RS assay testing from February 2005 to May 2015. Patients were assigned to risk categories based on the AAMC model. Using Kaplan-Meier methods, 5-year distant recurrence rates (DRR) were evaluated within each risk group and compared between AAMC and RS-defined risk groups. Five-year DRR were calculated for the P-G algorithm and compared with DRR for RS risk groups and the AAMC model's risk groups. Results: A total of 1268 cases were included. Five-year DRR were similar between the AAMC low-risk group (2.7%, n = 322) and the RS < 18 low-risk group (3.4%, n = 703), as well as between the AAMC high-risk group (22.8%, n = 230) and the RS > 30 high-risk group (23.0%, n = 141). Using the P-G algorithm, more patients were categorized as either low or high risk and the distant metastasis rate was 3.3% for the low-risk group (n = 739) and 24.2% for the high-risk group (n = 272). Using the P-G algorithm, 44% (552/1268) of patients would have avoided RS testing. Conclusions: AAMC model is capable of predicting 5-year recurrences in high- and low-risk groups similar to RS. Further, using the P-G algorithm, reserving RS for AAMC intermediate cases, results in larger low- and high-risk groups with similar prognostic accuracy. Thus, the P-G algorithm reliably identifies a significant portion of patients unlikely to benefit from RS assay and with improved ability to categorize risk.

Cross-sectional associations of albuminuria among Aboriginal and Torres Strait Islander adults: the eGFR Study.

OBJECTIVE: To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. METHODS: A cross-sectional analysis of Indigenous participants of the eGFR Study. MEASURES: Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. RESULTS: 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). CONCLUSION: Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Cardiovascular outcomes of Nephrotic syndrome in childhood (CVONS) study: a protocol for prospective cohort study.

BACKGROUND: Nephrotic syndrome (NS) is characterized by dyslipidemia which is a well-known risk factor for atherogenesis. Atherosclerosis in childhood is mostly subclinical and endothelial dysfunction is known to precede this. Evidence for screening for endothelial dysfunction and cardiovascular risk factors and early identification of premature onset of atherosclerosis in childhood NS remains tenuous in the absence of well-designed prospective studies addressing cardiovascular comorbidity in NS. The objective of our study is to examine endothelial dysfunction and short-term cardiovascular outcomes in a carefully phenotyped cohort of patients with Nephrotic syndrome as compared to healthy controls. METHODS: In a multi-centric prospective cohort study, 70 Steroid Resistant NS (SRNS), 70 Steroid Sensitive (SSNS) patients along with 70 Healthy Controls are being recruited. After a baseline assessment of functional and structural status of heart (2D Echocardiography), arteries (Carotid Doppler and Intima Media Thickness measurements) and microcirculation [a combination of 2D Echocardiography, Laser Doppler Flowmetry (LDF) and Brachial Artery Flow mediated dilation (FMD) and Nail Fold Capillaroscopy (NFC)], the patients are being investigated for endothelial dysfunction. Venous blood sample (15 ml) is being collected for routine investigations and assay of biochemical endothelial markers through Flow Cytometry. The patients will be followed up at 12 months and 24 months after the recruitment to look for any change from baseline period. DISCUSSION: This study will able to provide a better understanding of the epidemiology of endothelial dysfunction and associated subclinical cardiovascular co-morbidity in childhood NS. Findings on characterization of prevalence of endothelial dysfunction and subclinical markers may be used to design future randomized controlled trials for evaluating the efficacy of preventive and therapeutic interventions in reducing the incidence of cardiovascular disease.

A genomic approach to susceptibility and pathogenesis leads to identifying potential novel therapeutic targets in androgenetic alopecia.

We studied genome-wide gene expression from bald and haired scalp of individuals to evaluate pathogenic mechanisms underlying the development and progression of androgenetic alopecia (AGA). Unbiased analyses revealed a "bald pathology" based signature. Ontology enrichment analyses of the differentially expressed genes (DEGs) underscored apoptosis, cell proliferation, perturbed neurological pathways, and WNT signaling as central drivers of the hair loss process. Interactome analysis uncovered several known and novel key transcriptional regulators potentially affecting disease pathogenesis both within and "hidden" from the dataset. One DEG mapped within one of the fourteen identified transcriptionally active "hot spots" across the genome and coincided with a previous AGA-associated gene. The remaining DEGs within the "hot spots" offer an additional set of potential disease linked loci that may help to guide future studies aimed at identifying disease risk genes. Finally, we used in silico analyses to identify five molecular targets for exploration in future AGA therapies.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Competition and selectivity in supramolecular synthesis: structural landscape around 1-(pyridylmethyl)-2,2'-biimidazoles.

Three isomeric forms of 1-(pyridylmethyl)-2,2'-biimidazole, A1-A3, have been synthesized and subjected to systematic co-crystallizations with selected hydrogen- and halogen-bond donors in order to explore the impact of electrostatics and geometry on the resulting supramolecular architectures. The solid-state supramolecular behavior of A1-A3 is largely consistent in halogen-bonded co-crystals. Only two types of primary interactions, the N-HN/NH-N homomeric hydrogen-bond interactions responsible for the pairing of biimidazole moieties and the IN(pyridine) halogen bonds responsible for the co-crystal formation and structure extension, are present in these systems. The co-crystallizations with hydrogen-bond donors (carboxylic acids), however, lead to multiple possible structural outcomes because of the presence of the biimidazole-acid N-HO[double bond, length as m-dash]C/NH-O heterosynthon that can compete with biimidazole-biimidazole N-HN/NH-N homosynthon. In addition, the somewhat unpredictable nature of proton transfer makes the hydrogen-bonded co-crystals structurally less consistent than their halogen-bonded counterparts.

Development of a core outcome set for epilepsy in pregnancy (E-CORE): a national multi-stakeholder modified Delphi consensus study.

OBJECTIVE: To develop a set of core outcomes for studies on pregnant women with epilepsy. DESIGN: Delphi consensus study. POPULATION: Healthcare professionals, and patient representatives with lived experience of epilepsy in the UK. METHODS: We used a modified Delphi method and a consultation meeting to achieve consensus. Potential outcomes were identified by systematic review, and were scored using a Likert scale anchored between 1 (least important) and 5 (most important). We included outcomes that scored ≥4 by >70% of participants, and outcomes that scored ≤2 by <15% of participants. MAIN OUTCOME MEASURES: Outcomes in studies on epilepsy in pregnancy. RESULTS: Seventy-five healthcare professionals completed the first round, 48 (64%) completed the second round, and 37 (49%) completed the third round of the survey. Twenty-four patient representatives participated. The final core outcome set included 31 outcomes in three domains: neurological, offspring, and obstetric. Outcomes in the neurological domain were seizure control in pregnancy and postpartum, status epilepticus, maternal mortality, drowning, sudden unexpected death in epilepsy, postnatal depression, and quality of life. Offspring domain included congenital abnormalities (major and minor), fetal anticonvulsant syndrome, neurodevelopment, autism disorder, neonatal clinical complications, admission to a neonatal intensive care unit, and anthropometric measurements. The obstetric domain included live birth, stillbirth, miscarriage, ectopic, termination of pregnancy, admission to a high dependency or intensive care unit, breastfeeding, mode of delivery, preterm birth, pre-eclampsia, and eclampsia. Outcomes specific for studies on anti-epileptic drugs (AEDs) included maternal AED toxicity, AED compliance, neonatal withdrawal symptoms, and neonatal haemorrhagic disease. CONCLUSION: Embedding this core set in future clinical trials will promote the standardisation of reporting to inform clinical practice. TWEETABLE ABSTRACT: A Delphi method identifying core outcomes for epilepsy in pregnancy. Final core set includes 31 outcomes.

Biodegradation of anthracene by a newly isolated bacterial strain, Bacillus thuringiensis AT.ISM.1, isolated from a fly ash deposition site.

The current study is aimed to evaluate the mechanism of anthracene degradation by a bacterial strain isolated from fly ash deposition site near Jamadoba Coal Preparation Plant, Jharkhand, India. The Bushnell-Haas media cultured (containing anthracene as sole carbon source) bacterial isolate was identified by 16S rRNA gene sequence coding as the Bacillus thuringiensis strain, which showed the efficiency to degrade anthracene. The degradation efficiency of the strain has been estimated to be around 91% (for 40 mg l-1 of anthracene concentration) after 2 weeks of incubation at 33-36°C and initial pH of 6·8-7. The growth kinetics of the isolated strain has been described well by the Haldane-Andrews model of microbial growth pattern for inhibitory substrate, with a correlation factor (R2 value) of 0·9790. The maximum specific growth rate (µmax ) was 0·01053 h-1 and the value of inhibition coefficient for Haldane model was specified as 18·2448 mg l-1 . In the present study, some diphenol metabolites were identified besides the known possible biodegradation products. SIGNIFICANCE AND IMPACT OF THE STUDY: Polycyclic aromatic hydrocarbons (PAHs) are recognized as significant health risks and consequently listed as priority pollutants by environmental protection agencies across the globe. The aim of the present study was to degrade one of the important PAHs, anthracene, by a newly isolated Bacillus thuringiensis strain. This is the first report of anthracene degradation by B. thuringiensis. This is also the very first growth kinetic study of a bacteria in an anthracene-containing medium. Some diphenol metabolites were found for the first time as anthracene biodegradation by-products, which can be an indication towards a new pathway.