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Purpose: Topical glaucoma medication is the first line of management to reduce intraocular pressure (IOP) in patients with glaucoma. In this study, we intended to compare the ultrastructural findings of the cornea in patients with glaucoma before and after the reduction of the IOP through confocal microscopy. Methods: Ten patients (19 eyes) with newly diagnosed glaucoma were recruited from the glaucoma services of our tertiary care center. Demographic parameters were noted, and basic ocular examination, specular microscopy (Topcon SP3000P, Tokyo, Japan), and ultrasonic pachymetry (300 AP, Sonomed Escalon, Stoneham, MA, USA) were performed. In vivo confocal microscopy of corneal sections was performed using the z-ring Confoscan 4.0 (Nidek, Inc., Freemont, CA) at baseline and after 3 months of starting glaucoma medications. Results: The mean age of the patients was 53.53 ± 9.34 years. There was a statistically significant reduction (P < 0.0001) of IOP from 30.21 ± 7.42 mmHg (baseline) to 16.42 ± 4.14 mmHg (3 months). The mean central corneal thickness at baseline was 533.42 ± 3.96 µm, and it further decreased to 521.94 ± 42.45 µm at the end of 3 months (P = 0.006). No significant change was noted in the mean epithelial cell density, mean keratocyte density in anterior and posterior stroma, and the mean endothelial cell density and cell area (P >0.5). There was no significant percentage change in these parameters before and after the lowering of the IOP. Conclusion: A short-term (3 months) decrease in IOP using topical glaucoma medications caused a significant reduction in corneal thickness but did not have any significant ultrastructural changes in cornea measured using confocal microscopy.

Abstract To enhance the AlphaFold-Multimer-based protein complex structure prediction, we developed a quaternary structure prediction system (MULTICOM) to improve the input fed to AlphaFold-Multimer and evaluate and refine its outputs. MULTICOM samples diverse multiple sequence alignments (MSAs) and templates for AlphaFold-Multimer to generate structural predictions by using both traditional sequence alignments and Foldseek-based structure alignments, ranks structural predictions through multiple complementary metrics, and refines the structural predictions via a Foldseek structure alignment-based refinement method. The MULTICOM system with different implementations was blindly tested in the assembly structure prediction in the 15th Critical Assessment of Techniques for Protein Structure Prediction (CASP15) in 2022 as both server and human predictors. MULTICOM_qa ranked 3rd among 26 CASP15 server predictors and MULTICOM_human ranked 7th among 87 CASP15 server and human predictors. The average TM-score of the first predictions submitted by MULTICOM_qa for CASP15 assembly targets is ~0.76, 5.3% higher than ~0.72 of the standard AlphaFold-Multimer. The average TM-score of the best of top 5 predictions submitted by MULTICOM_qa is ~0.80, about 8% higher than ~0.74 of the standard AlphaFold-Multimer. Moreover, the Foldseek Structure Alignment-based Multimer structure Generation (FSAMG) method outperforms the widely used sequence alignment-based multimer structure generation.

Abstract Since the 14th Critical Assessment of Techniques for Protein Structure Prediction (CASP14), AlphaFold2 has become the standard method for protein tertiary structure prediction. One remaining challenge is to further improve its prediction. We developed a new version of the MULTICOM system to sample diverse multiple sequence alignments (MSAs) and structural templates to improve the input for AlphaFold2 to generate structural models. The models are then ranked by both the pairwise model similarity and AlphaFold2 self-reported model quality score. The top ranked models are refined by a novel structure alignment-based refinement method powered by Foldseek. Moreover, for a monomer target that is a subunit of a protein assembly (complex), MULTICOM integrates tertiary and quaternary structure predictions to account for tertiary structural changes induced by protein-protein interaction. The system participated in the tertiary structure prediction in 2022 CASP15 experiment. Our server predictor MULTICOM_refine ranked 3rd among 47 CASP15 server predictors and our human predictor MULTICOM ranked 7th among all 132 human and server predictors. The average GDT-TS score and TM-score of the first structural models that MULTICOM_refine predicted for 94 CASP15 domains are ~0.80 and ~0.92, 9.6% and 8.2% higher than ~0.73 and 0.85 of the standard AlphaFold2 predictor respectively.

This study extends our exploration of the potential of biomass ashes for their CO2-reactivity and self-cementing properties. The ability of three hardwood-based biomass ashes to mineralise CO2 gas and partially replace CEM I in mortars was investigated. The three hardwoods were English oak (Quercus rober), English lime (Tilia x europaea), and beech (Fagus sylvatica). The woody biomass wastes were incinerated at 800°C to extract their key mineral phases, which are known to be reactive to CO2 gas to form carbonates. The selected biomass ashes were analysed for their CO2-reactivity, which was in the range of 32–43% (w/w). The ashes were used to replace CEM I at 7 and 15% w/w and this “binder” was mixed with sand and water to produce cylindrical monolithic samples. These monoliths were then carbonated and sealed cured over 28 days. The compressive strength, density and microstructure of the carbonate-hardened monoliths were examined. The ash-containing monoliths displayed mature strengths comparable to the cement-only reference samples. The CO2 uptake of oak containing monoliths was 7.37 and 8.29% w/w, for 7 and 15% ash substitutions, respectively. For beech and English lime they were 4.96 and 6.22% w/w and 6.43 and 7.15% w/w, respectively. The 28 day unconfined compressive strengths for the oak and beech ashes were within the range of ~80–94% of the control, whereas lime ash was 107% of the latter. A microstructural examination showed carbonate cemented sand grains together highlighting that biomass ash-derived minerals can be very CO2 reactive and have potential to be used as a binder to produce carbonated construction materials. The use of biomass to energy ash-derived minerals as a cement replacement may have significant potential benefits, including direct and indirect CO2 emission savings in addition to the avoidance of landfilling of these combustion residues.

Objectives We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.Design Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.Setting 352 community family practices across 4 Canadian provinces between March 2017 and September 2020.Participants 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.Intervention Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.Primary and secondary outcome measures Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.Results At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected >600 million people in the ongoing global pandemic. Several variants of the SARS-CoV-2 have emerged in the last >2 years, challenging the continued efficacy of current COVID vaccines. Therefore, there is a crucial need to investigate a highly cross-protective vaccine effective against variants of SARS-CoV-2. In this study, we examined seven lipopeptides derived from highly conserved, immunodominant epitopes from the S, N, and M proteins of SARS-CoV-2, that are predicted to contain epitopes for clinically protective B cells, helper T cells (TH) and cytotoxic T cells (CTL). Intranasal immunization of mice with most of the lipopeptides led to significantly higher splenocyte proliferation and cytokine production, mucosal and systemic antibody responses, and induction of effector B and T lymphocytes in both lungs and spleen, compared to immunizations with the corresponding peptides without lipid. Immunizations with Spike-derived lipopeptides led to cross-reactive IgG, IgM and IgA responses against Alpha, Beta, Delta, and Omicron Spike proteins as well as neutralizing antibodies. These studies support their potential for development as components of a cross-protective SARS-CoV-2 vaccine.

The b-chromatic number b(G) of a graph G is the maximum k for which G has a proper vertex coloring using k colors such that each color class contains at least one vertex adjacent to a vertex of every other color class. In this paper, we have mainly investigated on the b-chromatic number of the Mycielskian of regular graphs. In particular, we have obtained the exact value of the b-chromatic number of the Mycielskian of some classes of graphs. This includes a few families of regular graphs, graphs with b(G) = 2 and split graphs. In addition, we have found bounds for the b-chromatic number of the Mycielskian of some more families of regular graphs in terms of the bchromatic number of their original graphs. Also we have found b-chromatic number of the generalized Mycielskian of some regular graphs.

Purpose: To report anterior-segment optical coherence tomography (ASOCT) characteristics of different types of corneal and anterior chamber (AC) foreign bodies (FBs) and their usefulness in diagnosis and management. Methods: This is a retrospective descriptive clinical study involving 11 eyes of 11 patients who presented at the outpatient department of a tertiary ophthalmic care center from January 2017 to January 2022. All patients had a diagnosed or suspected corneal FB. All participants underwent a comprehensive ophthalmological examination, followed by slit-lamp photography and ASOCT. FB removal was done where required by an external, internal, or combined approach. Results: The mean age of patients was 28.2 (7–53) years. Ten were male, and one was female. Seven patients had a definitive positive history of injury; in one, there was a history suggestive of trauma, one had the post-operative complication of scleral buckling surgery, and two patients had a history of insect fall in the eyes. Three patients had acute, four had sub-acute, and four had chronic presentations. Descemet's membrane (DM) breach was suspected in three cases of deep FB, which was later confirmed on ASOCT. In two cases, DM was presumed to be intact clinically, but ASOCT showed an AC penetration. The FB was removed in seven patients, one via slit-lamp, one via an external approach, two via an internal approach, and three via a combined approach. Conclusion: ASOCT facilitates non-invasive rapid imaging of ocular tissue at various depths, provides an accurate assessment of FB characteristics, and thereby serves as an additional tool in our armamentarium for diagnosis and management of deep corneal and AC FBs.

Background and Aim: Adjacent segment disease (ASD), radiological and clinical, is observed in many of the patients who undergo cervical inter-body fusion with/without graft, and with/without plating. This study aims to evaluate the proportion of ASD among patients who underwent cervical spine fusion surgery, to study the severity of degenerative radiographic findings at adjacent levels, and to determine sites and patterns of ASD. Methods and Materials/Patients: A descriptive study was performed on patients who underwent a previous cervical arthrodesis procedure in the last 2-5 years and continued follow-up as neurosurgery outpatients. A total of 59 patients who qualified for the inclusion criteria were included in the study. Results: Spine fixation was commonly performed at a single level mostly with sample size (54.2%, n=32) then at two levels (42.4%, n=25) and three levels (3.4%, n=2). Adjacent segment degeneration was present in the spine fixation level subgroup at a single level of 9 cases (28.12%), two levels of 9 cases (36%), and three-level fixations of 2 cases (100%). Six patients (10.2%) out of 59 patients developed radiculopathy. Among twenty-two cases (37.3%) with new changes at adjacent levels, reduced disc height was the most common one (18.6%, n=11). Anterior and posterior osteophytes with reduced disc height were found in 2 cases. Therefore, actual new changes were present in 20 cases only. The most common level of C4-C5 was observed for the development of ASD (13.6%, n=8). ASD developed at cranial to fusion in 13 cases (22%), caudal to fusion in 5 cases (8.5%), and at both levels in 2 patients. Conclusion: Adjacent segment disease was observed in a significant number of patients who underwent cervical spine surgery as evident from the results but only 6 out of 20 cases with radiological evidence of ASD were symptomatic. Changes were observed commonly at the C4/C5 level.

Background and Aim: Lumbar disc prolapse is a common cause of backache and radicular symptoms in lower limbs. Different surgical options have been described to compare the functional outcome, complications, and recurrence following surgery for lumbar disc prolapse by classical microlumbar discectomy (MLD) and minimally invasive tubular microdiscectomy. The advantages of one procedure over the other were also analyzed. Methods and Materials/Patients: A prospective, observational study conducted over a period of 1 year in the Department of Neurosurgery, Government Medical College Thiruvananthapuram, among patients who underwent surgical treatment for lumbar disc herniation by either microlumbar discectomy or minimally invasive surgery using a tubular retractor system. Ninety-nine patients who satisfied the inclusion and exclusion criteria were analyzed and tabulated for the outcome. Results: The two groups did not show a statistical difference in terms of functional outcome, complications, or recurrence rate. However, the need for post-operative analgesics, blood loss, and hence hospitalization was less in the tubular discectomy group. Conclusion: Both procedures are equally effective in terms of surgical results. However, the advantages and the subtle tendency of the patients to adopt “keyhole” make the tube an attractive option.

Disturbances in sleep/wake cycles are common among patients with neurodegenerative diseases including Huntington’s disease (HD) and represent an appealing target for chrono-nutrition-based interventions. In the present work, we sought to determine whether a low-carbohydrate, high-fat diet would ameliorate the symptoms and delay disease progression in the BACHD mouse model of HD. Adult WT and BACHD male mice were fed a normal or a ketogenic diet (KD) for 3 months. The KD evoked a robust rhythm in serum levels of β-hydroxybutyrate and dramatic changes in the microbiome of male WT and BACHD mice. NanoString analysis revealed transcriptional changes driven by the KD in the striatum of both WT and BACHD mice. Disturbances in sleep/wake cycles have been reported in mouse models of HD and are common among HD patients. Having established that the KD had effects on both the WT and mutant mice, we examined its impact on sleep/wake cycles. KD increased daytime sleep and improved the timing of sleep onset, while other sleep parameters were not altered. In addition, KD improved activity rhythms, including rhythmic power, and reduced inappropriate daytime activity and onset variability. Importantly, KD improved motor performance on the rotarod and challenging beam tests. It is worth emphasizing that HD is a genetically caused disease with no known cure. Life-style changes that not only improve the quality of life but also delay disease progression for HD patients are greatly needed. Our study demonstrates the therapeutic potential of diet-based treatment strategies in a pre-clinical model of HD.

Abstract Deep learning methods that achieved great success in predicting intrachain residue-residue contacts have been applied to predict interchain contacts between proteins. However, these methods require multiple sequence alignments (MSAs) of a pair of interacting proteins (dimers) as input, which are often difficult to obtain because there are not many known protein complexes available to generate MSAs of sufficient depth for a pair of proteins. In recognizing that multiple sequence alignments of a monomer that forms homomultimers contain the co-evolutionary signals of both intrachain and interchain residue pairs in contact, we applied DNCON2 (a deep learning-based protein intrachain residue-residue contact predictor) to predict both intrachain and interchain contacts for homomultimers using multiple sequence alignment (MSA) and other co-evolutionary features of a single monomer followed by discrimination of interchain and intrachain contacts according to the tertiary structure of the monomer. We name this tool DNCON2_Inter. Allowing true-positive predictions within two residue shifts, the best average precision was obtained for the Top-L/10 predictions of 22.9% for homodimers and 17.0% for higher-order homomultimers. In some instances, especially where interchain contact densities are high, DNCON2_Inter predicted interchain contacts with 100% precision. We also developed Con_Complex, a complex structure reconstruction tool that uses predicted contacts to produce the structure of the complex. Using Con_Complex, we show that the predicted contacts can be used to accurately construct the structure of some complexes. Our experiment demonstrates that monomeric multiple sequence alignments can be used with deep learning to predict interchain contacts of homomeric proteins.

Severe acute respiratory syndrome virus-2 (SARS-CoV-2), the causative infectious agent of the COVID-19 pandemic, has led to multiple (4-6) waves of infections worldwide during the past two years. The development of vaccines against SARS-CoV-2 has led to successful mass immunizations worldwide, mitigating the worldwide mortality due the pandemic to a great extent. Yet the evolution of new variants highlights a need to develop a universal vaccine which can prevent infections from all virulent SARS-CoV-2. Most of the current first generation COVID-19 vaccines are based on the Spike protein from the original Wuhan-hu-1 virus strain. It is encouraging that they still protect from serious illnesses, hospitalizations and mortality against a number of mutated viral strains, to varying degrees. Understanding the mechanisms by which these vaccines provide heterologous protection against multiple highly mutated variants can reveal strategies to develop a universal vaccine. In addition, many unexposed individuals have been found to harbor T cells that are cross-reactive against SARS-CoV-2 antigens, with a possible protective role. In this review, we will discuss various aspects of natural or vaccine-induced heterologous (cross-reactive) adaptive immunity against SARS-CoV-2 and other coronaviruses, and their role in achieving the concept of a pan-coronavirus vaccine.

Rishabha Malviya,1,* Shakshi Raj,1,* Shivkanya Fuloria,2,* Vetriselvan Subramaniyan,3,* Kathiresan Sathasivam,4 Usha Kumari,5 Dhanalekshmi Unnikrishnan Meenakshi,6 Omji Porwal,7 Darnal Hari Kumar,8 Amit Singh,1 Srikumar Chakravarthi,9 Neeraj Kumar Fuloria2,* 1Department of Pharmacy, SMAS, Galgotias University, Greater Noida, U.P., India; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Kedah, 08100, Malaysia; 3Department of Pharmacology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Kuala Lumpur, 42610, Malaysia; 4Department of Biotechnology, Faculty of Applied Science, AIMST University, Kedah, 08100, Malaysia; 5Department of Physiology, Faculty of Medicine, AIMST University, Kedah, 08100, Malaysia; 6Department of Pharmacology, College of Pharmacy, National University of Science and Technology, Muscat, 130, Oman; 7Department of Pharmacognosy, Faculty of Pharmacy, Tishk International University, Erbil, 44001, KRG, Iraq; 8Department of Pathology, Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Johor Bahru, 80200, Malaysia; 9Department of Pathology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Kuala Lumpur, 42610, Malaysia*These authors contributed equally to this workCorrespondence: Neeraj Kumar FuloriaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaTel +60 164037685Email neerajkumar@aimst.edu.myShivkanya FuloriaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaTel +60 143034057Email shivkanya_fuloria@aimst.edu.myPurpose: The present study was intended to fabricate chitosan (Ch)-tamarind gum polysaccharide (TGP) polyelectrolyte complex stabilized cubic nanoparticles of simvastatin and evaluate their potential against human breast cancer cell lines.Materials and Methods: The antisolvent precipitation method was used for formulation of nanoparticles. Factorial design (32) was utilized as a tool to analyze the effect of Ch and TGP concentration on particle size and entrapment efficiency of nanoparticles.Results: Formulated nanoparticles showed high entrapment efficiency (67.19± 0.42– 83.36± 0.23%) and small size (53.3– 383.1 nm). The present investigation involved utilization of two biological membranes (egg and tomato) as biological barriers for drug release. The study revealed that drug release from tomato membranes was retarded (as compared to egg membranes) but the release pattern matched that of egg membranes. All formulations followed the Baker–Lansdale model of drug release irrespective of the two different biological barriers. Stability studies were carried out for 45 days and exhibited less variation in particle size as well as a reduction in entrapment efficiency. Simvastatin loaded PEC stabilized nanoparticles exhibited better control on growth of human breast cancer cell lines than simple simvastatin. An unusual anticancer effect of simvastatin nanoparticles is also supported by several other research studies.Conclusion: The present study involves first-time synthesis of Ch-TGP polyelectrolyte complex stabilized nanoparticles of simvastatin against MCF-7 cells. It recommends that, in future, theoretical modeling and IVIVC should be carried out for perfect designing of delivery systems.Keywords: polysaccharide, polyelectrolyte, cubic nanoparticles, simvastatin, breast cancer, tamarind

Immune thrombocytopenia (ITP) is a rare paraneoplastic syndrome of solid tumor malignancies. In previously described cases of renal cell carcinoma (RCC) associated with secondary ITP, treatment has consisted of nephrectomy, splenectomy, and corticosteroids. Here, we describe a case of metastatic RCC presenting with a right ventricular mass and subsequent development of secondary ITP. The clinical course was complicated by recurrent severe thrombocytopenia despite treatment with corticosteroids, rituximab, and thrombopoietin receptor agonists, precluding cancer-directed therapy and anticoagulation. Further study is needed to determine the optimal management strategy for malignancy-associated ITP.

Abstract Background Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectases and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. The primary objective of this study was to ascertain the relationship between epistaxis severity scores (ESS), laboratory values, genotype, and phenotype in HHT. Our secondary objective was to assess efficacy of systemic antifibrinolytic therapy in reducing ESS in HHT. Methodology We conducted a retrospective review of patients seen at the UNC HHT Center from January 1, 2009 to February 28, 2015. ESS, demographics, and results of genetic testing were abstracted from the medical record. Response to antifibrinolytic therapy was evaluated by comparing pre-post ESS. Results One hundred and forty nine patients were eligible with 116 having genetic testing and 33 without. Age, hemoglobin and ferritin levels were predictive of ESS. Of the 116 patients that underwent genetic testing: 63 had an ACVRL1 mutation, 40 had an ENG mutation, 2 had a SMAD4 mutation, and 11 patients had no pathologic HHT genetic variation detected. Compared to patients without a detectable HHT-associated genetic variation, patients with a HHT-associated genetic variation had higher ESS scores (p 4 were started on antifibrinolytic therapy (tranexamic acid or aminocaproic acid) and had a post-treatment ESS recorded. All patients had a decrease in ESS of > 0.71 (minimal meaningful difference), but patients taking antifibrinolytics displayed larger decreases. No patients on antifibrinolytics experienced a VTE with median follow up of 13 months. Conclusions We demonstrate that the ESS correlates with age, hemoglobin and ferritin. Additionally, we demonstrate that HHT patients with genetic mutations have higher ESS scores. Our data demonstrate that antifibrinolytics are effective in decreasing epistaxis severity and safe with long-term use in HHT patients.

Abstract Introduction We conducted a longitudinal study in patients with pancreatic and colorectal cancer. We determined the effect of chemotherapy on extracellular vesicle tissue factor (EVTF) activity and the association of plasma EVTF activity with venous thromboembolism (VTE) and survival. Material and Methods We enrolled 13 patients with pancreatic and 22 patients with colorectal cancer. Plasma samples were collected during the 85‐day study period. Patients were followed for 3 months after the study period. We recorded symptomatic VTE during the study period (3 months) or asymptomatic deep vein thrombosis detected by ultrasound at day 85. We measured EVTF activity before and after chemotherapy. Results and Conclusions In the pancreatic cancer group, 2 patients had elevated levels of EVTF activity. One of these patients developed symptomatic VTE and died, and the second patient did not have a VTE but died. Chemotherapy decreased EVTF activity in 2 pancreatic patients with high levels. In the colorectal cancer group, 4 patients developed VTE, but EVTF activity was not elevated in any patient and no patient died. We observed a borderline significant correlation between EVTF activity and D‐dimer in the patients with pancreatic but not colorectal cancer. In this small descriptive study, 2 patients with pancreatic cancer had an elevated level of EVTF activity. Both patients died during the study period, and one had a VTE. Chemotherapy decreased EVTF activity in these patients. In contrast, elevated levels of EVTF activity were not observed in patients with colorectal cancer with or without VTE.

Canisters are used to store liquids such as oil, paint, liquefied glue, and so on. When a customer buys a canister of liquid, they expect the contents to be in pristine condition. The contents of the canister may become defective due to errors in manufacture, transportation, or unfavourable climatic conditions, and the unsuspecting client discovers this after breaking the seal. The vendor will not take the defective goods back after the seal has been broken. One such process that can be used to determine that the products in the canisters are in usable condition is non-destructive testing using ultrasonics. In this method, a transducer is used, which has a transmitter and a receiver. The transmitter is placed on one side of the canister, and the receiver is placed exactly opposite on the other side. Using this, the time taken for the waves to propagate from emitter to receiver (time of flight) is noted and compared with that of standard values. This process allows us to determine whether the contents of the canisters are in good condition or not. The measurements are carried out at three different locations, i.e., the top, middle, and bottom of the canister, and time of flight (TOF) values are recorded. If the content inside the canister is in a liquid state, the TOF is observed at about 54±0.5 microseconds. Due to poor weather conditions, mismanufacturing, or mishandling in transportation, if the canister’s contents have any air pockets, then the contents react and solidify. For this case, the TOF is about 40 ±0.5 microseconds only. A difference of 14 microseconds was observed when the content of the canister changed from liquid sate to solid. This allows us to determine the contents of the canister, without opening the seal.

Abstract Mining and related activities cause severe degradation of ambient air quality. A study of particulate matter (PM) across transportation, mining and control (C) sites for dust attenuation capacity (DAC) in selected tree species were carried out in Jharia coalfield (JCF) to estimate the menace of dust pollution and also to measure air pollution tolerance index (APTI). Results indicated that the maximum value of PM10 and PM2.5 ranged from 54 to 174 and 29 to 78 μg m− 3 respectively across all the sites. The maximum values occurred in transportation and the minimum at C for both the particulates. Mining and transportation resulted in an increase in PM10 values by 161 and 200% and PM2.5 values by 100 and 136% respectively as compared to those in C. The mean concentration of PM10 and PM2.5 across the sites exceeded the permissible limit of 100 and 60 μg m− 3 respectively. Transportation was worse than mining due to the high proportion of hazardous fine (PM2.5) particulates. DAC indicated that Tectona grandis (TG) captured maximum dust (2.15 mg cm− 2) with 85% and Peltophorum inerme (PI) the minimum (0.15 mg cm− 2) with 5% efficiency. The trend for DAC showed TG > Ficus glomerata (FG) > Psidium guajava (PG) > Ficus benghalensis (FB) > Ficus religiosa (FR) > Alstonia scholaris (AS) > Aegle marmelos (AM) > Gmelina arborea (GA) > Dalbergia sissoo (DS) > Syzyzium cumini (SC) > Azadirachta indica (AI) > Terminalia arjuna (TA) > Mangifera indica (MI) > Albizia lebbeck (AL) > PI in descending order. APTI based on pH, total chlorophyll, ascorbic acid and relative water content indicated maximum values for TG (17) with 90% and minimum for PI (10) with 57% of the total and is a measure of the sustainability of plants in JCF. The descending order for APTI was TG > PG > FG > FR > FB > AI > MI > SC > DS > GA > AM > AS > AL > TA > PI. Thus, TG is the most suitable and PI the least. Stomatal density is negatively related to DAC and positively related to APTI. DAC therefore, cannot be attributed to a single factor but a mix of complex factors such as morphological and anatomical characteristics of the leaf, particle size, species type, metabolism, location, meteorology and stress conditions. Based on the findings a greenbelt design was proposed to improve the air quality of the mining and transportation areas.

Individuals affected by Huntington's disease (HD) present with progressive degeneration that results in a wide range of symptoms, including cardiovascular (CV) dysfunction. The huntingtin gene (HTT) and its product are ubiquitously expressed, hence, the cardiomyopathy could also be driven by defects caused by its mutated form (mHTT) in the cardiomyocytes themselves. In the present study, we sought to determine the contribution of the mHTT expressed in the cardiomyocytes to CV symptoms. We utilized the BACHD mouse model, which exhibits many of the HD core symptoms, including CV dysfunction. This model allows the targeted genetic reduction of mHTT expression in the cardiomyocytes while maintaining the expression of the mHTT in the rest of the body. The BACHD line was crossed with a line of mice in which the expression of Cre recombinase is driven by the cardiac-specific alpha myosin-heavy chain (Myh6) promoter. The offspring of this cross (BMYO mice) exhibited a dramatic reduction in mHTT in the heart but not in the striatum. The BMYO mice were evaluated at 6 months old, as at this age, the BACHD line displays a strong CV phenotype. Echocardiogram measurements found improvement in the ejection fraction in the BMYO line compared to the BACHD, while hypertrophy was observed in both mutant lines. Next, we examined the expression of genes known to be upregulated during pathological cardiac hypertrophy. As measured by qPCR, the BMYO hearts exhibited significantly less expression of collagen1a as well as Gata4, and brain natriuretic peptide compared to the BACHD. Fibrosis in the hearts assessed by Masson's trichrome stain and the protein levels of fibronectin were reduced in the BMYO hearts compared to BACHD. Finally, we examined the performance of the mice on CV-sensitive motor tasks. Both the overall activity levels and grip strength were improved in the BMYO mice. Therefore, we conclude that the reduction of mHtt expression in the heart benefits CV function in the BACHD model, and suggest that cardiomyopathy should be considered in the treatment strategies for HD.

Proteins interact to form complexes. Predicting the quaternary structure of protein complexes is useful for protein function analysis, protein engineering, and drug design. However, few user-friendly tools leveraging the latest deep learning technology for inter-chain contact prediction and the distance-based modelling to predict protein quaternary structures are available. To address this gap, we develop DeepComplex, a web server for predicting structures of dimeric protein complexes. It uses deep learning to predict inter-chain contacts in a homodimer or heterodimer. The predicted contacts are then used to construct a quaternary structure of the dimer by the distance-based modelling, which can be interactively viewed and analysed. The web server is freely accessible and requires no registration. It can be easily used by providing a job name and an email address along with the tertiary structure for one chain of a homodimer or two chains of a heterodimer. The output webpage provides the multiple sequence alignment, predicted inter-chain residue-residue contact map, and predicted quaternary structure of the dimer. DeepComplex web server is freely available at http://tulip.rnet.missouri.edu/deepcomplex/web_index.html

Background Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.Methods We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.Results We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).Conclusions The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

Introduction Hypertension is a common public health problem and a key modifiable risk factor for cardiovascular (CV) and chronic kidney disease (CKD). Home blood pressure (BP) telemonitoring (HBPT) and management is associated with improved BP control, accelerated delivery of care and decision-making strategies that can reduce adverse outcomes associated with hypertension. The aim of this paper is to describe the protocol for a systematic review to assess the impact of HBPT interventions used for improving BP control and reducing CV and kidney outcomes in non-dialysis CKD patients.Methods We developed this protocol using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO and grey literature for studies conducted in non-dialysis CKD patients on interventions using HBPT and reporting outcomes related to BP control and other outcomes such as CV events and kidney disease progression. All studies meeting these criteria, in adults and published from inception until 2020 with no language barrier will be included.Ethics and dissemination Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of HBPT on BP control in non-dialysis CKD patients, evidence gathered through it will be disseminated using traditional approaches that includes open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate government agencies.PROSPERO registration number CRD42020190705).

COVID-19 is pandemic, and likely to become endemic, possibly returning with greater virulence. Outlining potential public health actions, including hygiene measures, social distancing and face masks, and realistic future advances, this paper focuses on the consequences of taking no public health action; the role of natural changes such as weather; the adverse public health consequences of lockdowns; testing for surveillance and research purposes; testing to identify cases and contacts, including the role of antibody tests; the public health value of treatments; mobilising people who have recovered; population (a synonym for herd) immunity through vaccination and through natural infection; involving the entire population; and the need for public debate. Until there is a vaccine, population immunity is going to occur only from infection. Allowing infection in those at very low risk while making it safer for them and wider society needs consideration but is currently taboo. About 40–50% population immunity is sufficient to suppress an infection with a reproduction number of about 1 or slightly more. Importantly, in children and young people COVID-19 is currently rarely fatal, roughly comparable with influenza. The balance between the damage caused by COVID-19 and that caused by lockdowns needs quantifying. Public debate, including on population immunity, informed by epidemiological data, is now urgent.

Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p

[This corrects the article DOI: 10.1371/journal.pone.0211032.].

Surgeons are increasingly treating seniors with complex care needs who are at high-risk of readmission and functional decline. Yet, the prognostic importance of post-operative mobilization in older surgical patients is under-investigated and remains unclear. Thus, we evaluated the relationship between post-operative mobilization and events after hospital discharge in older people. Overall, 306 survivors of emergency abdominal surgery aged ≥65y who required help with

The potential of genomic medicine in improving the quality of healthcare both at population and individual-level is well-recognized globally. However, successful adoption of genetic and genomic evidence into clinical practice depends on training the healthcare workforce and clinical researchers in genomic medicine. Due to limited expertise in the medical genetics and genomics field, widespread uptake largely depends on task-shifting for the implementation of genomic medicine implementation to key healthcare professionals such as nurses. Their knowledge would be developed through courses aimed at professional development. Globally, trainers, and training initiatives in genomic medicine are in early stages of development, but resource limited settings such as the African continent face additional logistical and institutional challenges. The African Genomic Medicine Training (AGMT) Initiative was conceived during a combined conference of the African Society of Human Genetics (AfSHG) and the Human Heredity and Health in Africa Consortium (H3Africa) in 2016, Senegal, in response to the needs for developing knowledge and skills in genomic medicine. AGMT was established to implement a sustainable genomic medicine training initiative primarily for healthcare professionals who are not geneticists but are nurses, doctors, and pharmacists in Africa. This paper reports on the establishment of the AGMT initiative and the strategies developed and piloted by this initiative in designing and implementing an accredited frame-work and community-based blended learning course for nurses across 11 African countries. The global implementation experiences, outcomes and lessons learnt are highlighted. The AGMT initiative strategy takes advantage of existing research consortia and networks to train and create a pool of trainers and has adopted evidence-based approaches to guide curriculum and content development/adaptation. This initiative established the first Africa-wide online blended learning genomic medicine course which forms the basis from which to develop courses for other healthcare professionals and the wider public.

Seven isolates from spoiled fruits and vegetables were screened for pectinase produc¬tion using pectin agar plates and the most efficient bacterial strain, MPTD1, was identified as Bacillus sonorensis. Optimisation of various process parameters was done using Plack¬ett-Burman and Box-Behnken designs and it was found that parameters like yeast extract, K2HPO4, incubation time, NaNO3 and KCl have a negative impact on pectinase production. Parameters like pH and MgSO4 and pectin mass fractions have a positive impact on pecti¬nase production. The maximum obtained enzyme activity was 2.43 (μM/mL)/min. This is the first report on pectinase production by Bacillus sonorensis.

Abstract We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P

Epithelioid hemangioendothelioma is an uncommon vascular neoplasm. It is rare in the intracranial location. Its occurrence in the region of cavernous sinus is reported only once. Here, we report a case of 49-year-old man who presented with a headache, pain in the right eye, diplopia, and ptosis due to third and sixth cranial nerve involvement. Imaging showed an enhancing lesion in the region of cavernous sinus on the right side. Pterional craniotomy, combined extradural and intradural approach, and subtotal excision of the tumor was done. Histopathology and immunohistochemistry were suggestive of epithelioid hemangioendothelioma which is a rare tumor in this location. We report this case because of its rarity and uncommon location.

Abstract Intramedullary spinal cord abscess is a rare infection of the spinal cord with less than 120 cases reported since its first description by Hart in 1830. It is usually associated with abnormalities of the spinal cord or documented source of infection or immunodeficiency, requiring clinical radiological suspicion for accurate diagnosis. The first case is a middle-aged healthy woman without any underlying risk factors, presented with progressive paraparesis, in whom prompt, accurate diagnosis with contrast magnetic resonance imaging, diffusion-weighted imaging, and apparent diffusion coefficient mapping followed by early surgery was possible, which resulted in the favorable neurological outcome. The second case is a 10-year-old boy with paraparesis whose definite treatment and surgery was delayed due to a delay in accurate clinical and radiological diagnosis which resulted in poor outcomes. Hence, we try to establish that prompt diagnosis and surgical treatment can result in a favorable neurological outcome, though the prognosis, in general, is poor in this clinical condition. A review of literature in support of our cases is given.

Introduction: Ovarian follicle growth is a key step in the success of assisted reproductive treatment, but limited data exists to directly relate follicle growth to recombinant FSH (rFSH) dose. In this study, we aim to evaluate FSH requirements for follicular growth during controlled ovarian stimulation.Method: Single center retrospective cohort study of 1,034 IVF cycles conducted between January 2012–January 2016 at Hammersmith Hospital IVF unit, London, UK. Median follicle size after 5 days of stimulation with rFSH and the proportion of antral follicles recruited were analyzed in women treated with rFSH alone to induce follicular growth during IVF treatment.Results: Starting rFSH dose adjusted for body weight (iU/kg) predicted serum FSH level after 5 days of rFSH (r2 = 0.352, p < 0.0001), median follicle size after 5 days of rFSH, and the proportion of antral follicles recruited by the end of stimulation. Day 5 median follicle size predicted median follicle size on subsequent ultrasound scans (r2 = 0.58–0.62; p < 0.0001), and hence time to oocyte maturation trigger (r2 = 0.22, P < 0.0001). Insufficient rFSH starting dose that required >5% dose-increase was associated with increased variability in follicle size on the day of oocyte maturation trigger, and negatively impacted the number of mature oocytes retrieved.Conclusion: Weight-adjusted rFSH dose correlates with follicular growth during ovarian stimulation. Early recruitment of follicles using a sufficient dose of rFSH from the start of stimulation was associated with reduced variability in follicle size at time of oocyte maturation trigger and an increased number of mature oocytes retrieved.

BACKGROUND AND OBJECTIVES:Management of hypertension in chronic kidney disease (CKD) remains a major challenge. We conducted a systematic review to assess whether exercise is an effective strategy for lowering blood pressure in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS:We searched MEDLINE, EMBASE, the Cochrane Library, CINAHL and Web of Science for randomized controlled trials (RCTs) that examined the effect of exercise on blood pressure in adults with non-dialysis CKD, stages 3-5. Outcomes were non-ambulatory systolic blood pressure (primary), other blood pressure parameters, 24-hour ambulatory blood pressure, pulse-wave velocity, and flow-mediated dilatation. Results were summarized using random effects models. RESULTS:Twelve studies with 505 participants were included. Ten trials (335 participants) reporting non-ambulatory systolic blood pressure were meta-analysed. All included studies were a high risk of bias. Using the last available time point, exercise was not associated with an effect on systolic blood pressure (mean difference, MD -4.33 mmHg, 95% confidence interval, CI -9.04, 0.38). The MD after 12-16 and 24-26 weeks of exercise was significant (-4.93 mmHg, 95% CI -8.83, -1.03 and -10.94 mmHg, 95% CI -15.83, -6.05, respectively) but not at 48-52 weeks (1.07 mmHg, 95% CI -6.62, 8.77). Overall, exercise did not have an effect on 24-hour ambulatory blood pressure (-5.40 mmHg, 95% CI -12.67, 1.87) or after 48-52 weeks (-7.50 mmHg 95% CI -20.21, 5.21) while an effect was seen at 24 weeks (-18.00 mmHg, 95% CI -29.92, -6.08). Exercise did not have a significant effect on measures of arterial stiffness or endothelial function. CONCLUSION:Limited evidence from shorter term studies suggests that exercise is a potential strategy to lower blood pressure in CKD. However, to recommend exercise for blood pressure control in this population, high quality, longer term studies specifically designed to evaluate hypertension are needed.

A b-coloring of a graph G with k colors is a proper coloring of G using k colors in which each color class contains a color dominating vertex, that is, a vertex which has a neighbor in each of the other color classes. The largest positive integer k for which G has a b-coloring using k colors is the b-chromatic number b(G) of G. In this paper, we obtain bounds for the b- chromatic number of induced subgraphs in terms of the b-chromatic number of the original graph. This turns out to be a generalization of the result due to R. Balakrishnan et al. [Bounds for the b-chromatic number of G−v, Discrete Appl. Math. 161 (2013) 1173-1179]. Also we show that for any connected graph G and any e ∈ E(G), b(G - e) ≤ b(G) + -2. Further, we determine all graphs which attain the upper bound. Finally, we conclude by finding bound for the b-chromatic number of any subgraph.

Abstract Background The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY). Methods A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m2) were recruited between 10–26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant’s length and weight, woman’s BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content. Results Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1–12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of −0.25 standard deviation scores for infant weight at 12 months (95 % CI: −0.16–0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported. Conclusions The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial. Trial Registration Current Controlled Trials ISRCTN56735429

Summary: Background: Ethnic minorities often experience barriers to health care. We studied six established quality indicators of health-system performance across ethnic groups in Scotland. Methods: In this population-based cohort study, we linked ethnicity from Scotland's Census 2001 (April 29, 2001) to hospital admissions and mortality records, with follow-up until April 30, 2013. Indicators of health-system performance included amenable deaths (ie, deaths avertable by effective treatment), preventable deaths (ie, deaths avertable by public health policy), avoidable deaths (combined amenable and preventable deaths), avoidable hospital admissions, unplanned readmissions, and length of stay. We calculated rate ratios and odds ratios (with 95% CIs) using Poisson and logistic regression, which we multiplied by 100, adjusting first for age-related covariates and then for socioeconomic-related and birthplace-related covariates. The white Scottish population was the reference (rate ratio [RR] 100). Findings: The results are based on 4·61 million people. During the 50·5 million person-years of study, 1·17 million avoidable hospital admissions, 587 740 unplanned readmissions, and 166 245 avoidable deaths occurred. South Asian groups had higher avoidable hospital admissions than the white Scottish group, with the highest reported RRs in Pakistani groups (RR 140·6 [95% CI 131·9–150·0] in men; RR 141·0 [129·0–154·1] in women). There was little variation between ethnic groups in length of stay or unplanned readmission. Preventable and amenable mortality were higher in the white Scottish group than several ethnic minorities including other white British, other white, Indian, and Chinese groups. Such differences were partly diminished by adjustment for socioeconomic status, whereas adjustment for country of birth had little additional effect. Interpretation: These data suggest concerns about the access to and quality of primary care to prevent avoidable hospital admissions, especially for south Asians. Relatively high preventable and amenable deaths in white Scottish people, compared with several ethnic minority populations, were unexpected. Future studies should both corroborate and examine explanations for these patterns. Studies using several indicators simultaneously are also required internationally. Funding: Chief Scientist's Office, Medical Research Council, NHS Research Scotland, Farr Institute.