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Summary: TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of TSPEAR is unknown. The clinical features, the mutation spectrum, and the underlying mechanisms of ARED14 are poorly understood. Combining data from new and previously published individuals established that ARED14 is primarily characterized by dental anomalies such as conical tooth cusps and hypodontia, like those seen in individuals with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed that most of the pathogenic TSPEAR missense variants likely destabilize the β-propeller of the protein. Analysis of 100000 Genomes Project (100KGP) data revealed multiple founder TSPEAR variants across different populations. Mutational and recombination clock analyses demonstrated that non-Finnish European founder variants likely originated around the end of the last ice age, a period of major climatic transition. Analysis of gnomAD data showed that the non-Finnish European population TSPEAR gene-carrier rate is ∼1/140, making it one of the commonest AREDs. Phylogenetic and AlphaFold structural analyses showed that TSPEAR is an ortholog of drosophila Closca, an extracellular matrix-dependent signaling regulator. We, therefore, hypothesized that TSPEAR could have a role in enamel knot, a structure that coordinates patterning of developing tooth cusps. Analysis of mouse single-cell RNA sequencing (scRNA-seq) data revealed highly restricted expression of Tspear in clusters representing enamel knots. A tspeara−/−;tspearb−/− double-knockout zebrafish model recapitulated the clinical features of ARED14 and fin regeneration abnormalities of wnt10a knockout fish, thus suggesting interaction between tspear and wnt10a. In summary, we provide insights into the role of TSPEAR in ectodermal development and the evolutionary history, epidemiology, mechanisms, and consequences of its loss of function variants.

BackgroundPatients admitted to hospital with sepsis are at persistent risk of poor outcome after discharge. Many tools are available to risk-stratify sepsis patients for in-hospital mortality. This study aimed to identify the best risk-stratification tool to prognosticate outcome 180 days after admission via the emergency department (ED) with suspected sepsis.MethodsA retrospective observational cohort study was performed of adult ED patients who were admitted after receiving intravenous antibiotics for the treatment of a suspected sepsis, between 1st March and 31st August 2019. The Risk-stratification of ED suspected Sepsis (REDS) score, SOFA score, Red-flag sepsis criteria met, NICE high-risk criteria met, the NEWS2 score and the SIRS criteria, were calculated for each patient. Death and survival at 180 days were noted. Patients were stratified in to high and low-risk groups as per accepted criteria for each risk-stratification tool. Kaplan–Meier curves were plotted for each tool and the log-rank test performed. The tools were compared using Cox-proportional hazard regression (CPHR). The tools were studied further in those without the following specified co-morbidities: Dementia, malignancy, Rockwood Frailty score of 6 or more, long-term oxygen therapy and previous do-not-resuscitate orders.ResultsOf the 1,057 patients studied 146 (13.8%) died at hospital discharge and 284 were known to have died within 180 days. Overall survival proportion was 74.4% at 180 days and 8.6% of the population was censored before 180 days. Only the REDS and SOFA scores identified less than 50% of the population as high-risk. All tools except the SIRS criteria, prognosticated for outcome at 180 days; Log-rank tests between high and low-risk groups were: REDS score p

Upper: Giant impact (Courtesy NASA/JPL-Caltech); chondrule, majorite in shocked enstatite (Courtesy Miyahara); Lower: Collision of planetesimals (Courtesy NASA/JPL-Caltech); Raman mapping of wadsleyite and ringwoodite in Peace River L6 (Courtesy Miyahara and El Goresy).

Abstract Purpose: Multiple glaucoma treatment modalities seek to lower IOP by bypassing or removing a portion of the juxtacanalicular trabecular meshwork. These procedures often require expensive implants or specialized surgical instruments. The authors developed a technique for ab interno goniectomy utilizing a standard disposable 25-gauge hypodermic needle. The surgical procedure—termed bent ab interno needle goniectomy (BANG)—and preliminary results are presented here. Methods: A retrospective chart review was performed for all patients who underwent goniotomy using a modified hypodermic needle by one of the three authors between July 2017 and June 2018. The mean and standard deviation pre- and postoperative IOP and the number of glaucoma medications were calculated. The student paired t-test was used to compare pre- and postoperative data. A P-value of < 0.05 was considered statistically significant. Results: At postoperative month six, the mean IOP was 13.3 ± 2.5 mmHg (P = 3.6 × 10 - 7 ) on 0.5 ± 0.8 topical glaucoma medications (P = 0.01). A ≥ 20% reduction in IOP was achieved in 73% of patients. Seventy-three percent of patients required ≥ 1 fewer medication, while 73% of patients required no medications for IOP control. Forty-one percent of those treated achieved IOP ≤ 12 mmHg. Conclusion: The BANG procedure is a low-cost MIGS technique available to surgeons around the world with preliminary outcomes similar to more expensive alternatives.

Breast cancer (BCa) has many well-known risk factors, including age, genetics, lifestyle, and diet; however, the influence of the gut microbiome on BCa remains an emerging area of investigation. This study explores the connection between the gut microbiome, dietary habits, and BCa risk. We enrolled newly diagnosed BCa patients and age-matched cancer-free controls in a case-control study. Comprehensive patient data was collected, including dietary habits assessed through the National Cancer Institute Diet History Questionnaire (DHQ). 16S rRNA amplicon sequencing was used to analyze gut microbiome composition and assess alpha and beta diversity. Microbiome analysis revealed differences in the gut microbiome composition between cases and controls, with reduced microbial diversity in BCa patients. The abundance of three specific microbial genera—Acidaminococus, Tyzzerella, and Hungatella—was enriched in the fecal samples taken from BCa patients. These genera were associated with distinct dietary patterns, revealing significant associations between the presence of these genera in the microbiome and specific HEI2015 components, such as vegetables and dairy for Hungatella, and whole fruits for Acidaminococus. Demographic characteristics were well-balanced between groups, with a significantly higher body mass index and lower physical activity observed in cases, underscoring the role of weight management in BCa risk. Associations between significant microbial genera identified from BCa cases and dietary intakes were identified, which highlights the potential of the gut microbiome as a source of biomarkers for BCa risk assessment. This study calls attention to the complex interplay between the gut microbiome, lifestyle factors including diet, and BCa risk.

The efficacy of therapeutic T-cells is limited by a lack of positive signals and excess inhibitory signaling in tumor microenvironments. We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing chimeric antigen receptors (CARs), and C7R-modified GD2.CAR T-cells are currently undergoing clinical trials. To determine if the C7R could also enhance the activity of T-cells recognizing tumors via their native T-cell receptors (TCRs), we evaluated its effects in Epstein–Barr virus (EBV)-specific T-cells (EBVSTs) that have produced clinical benefits in patients with EBV-associated malignancies. EBVSTs were generated by stimulation of peripheral blood T-cells with overlapping peptide libraries spanning the EBV lymphoma antigens, LMP1, LMP2, and EBNA 1, followed by retroviral vector transduction to express the C7R. The C7R increased STAT5 signaling in EBVSTs and enhanced their expansion over 30 days of culture in the presence or absence of exogenous cytokines. C7R-EBVSTs maintained EBV antigen specificity but were dependent on TCR stimulation for continued expansion. C7R-EBVSTs produced more rapid lymphoma control in a murine xenograft model than unmodified EBVSTs and persisted for longer. The findings have led to a clinical trial, evaluating C7R-EBVSTs for the treatment of refractory or relapsed EBV-positive lymphoma (NCT04664179).

(1) Background: Frequent exposure to ionising radiation is often used to determine the diagnosis of adolescent idiopathic scoliosis (AIS), a lateral curvature of the spine in those aged between 10 and 18 years, and a treatment plan according to Cobb angle. This narrative review outlines the clinical utility of surface topography (ST), a radiation-free imaging modality. (2) Methods: Publicly available databases were searched to yield literature related to ST. Identified articles were classified based on the equipment used and in order of how it was developed, i.e., historical, recent developments, and state-of-the-art developments. (3) Conclusions: ST is a reliable cost-effective non-invasive technique that provides an alternative to radiation-based imaging to aid with the diagnosis and potential screening of AIS. Several scanning methods are available, which allows ST to be used in several clinical environments. Limitations of inter-reliability and differences of apparatus resulting in variations of data have been noted through this narrative review.

Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque’s fibrous cap thickness, and reduced necrotic core, macrophage content, and cell apoptosis, consistent with promotion of a stable plaque phenotype. IGF-1 reduced circulating triglycerides, markers of systemic oxidative stress, and CXCL12 chemokine levels. We used spatial transcriptomics (ST) to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. ST analysis showed that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque macrophages, suggesting possible involvement of these molecules in IGF-1’s effect on atherosclerosis. Thus, IGF-1 reduced coronary plaque burden and promoted features of stable plaque in a pig model, providing support for consideration of clinical trials.

Leishmaniasis is a neglected tropical disease with three main clinical types; cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). CL and MCL are considered to be highly stigmatizing due to potentially disfiguring skin pathology. CL and MCL-associated stigma are reported across the world in different contexts assimilating different definitions and interpretations. Stigma affects people with CL, particularly in terms of quality of life, accessibility to treatment, and psycho-social well-being. However, evidence on CL- and MCL-associated stigma is dispersed and yet to be synthesized. This systematic review describes the types, measurements, and implications of the stigma associated with CL and MCL and identifies any preventive strategies/interventions adopted to address the condition. This study was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement which is registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols PROSPERO (ID- CRD42021274925). We will perform an electronic search in MEDLINE, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library databases, and in Google Scholar, using a customized search string. Any article that discusses any type of CL- and/or MCL-associated stigma in English, Spanish and Portuguese will be included. Articles targeting veterinary studies, sandfly vector studies, laboratory-based research and trials, articles focusing only on visceral leishmaniasis, and articles on diagnostic or treatment methods for CL and MCL will be excluded. Screening for titles and abstracts and full articles and data extraction will be conducted by two investigators. The risk of bias will be assessed through specific tools for different study types. A narrative synthesis of evidence will then follow. This review will identify the knowledge gap in CL-associated stigma and will help plan future interventions.

IntroductionExcess body weight causes 4 million deaths annually across the world. The number of people affected by humanitarian crises stands at a record high level with 1 in 95 people being forcibly displaced. These epidemics overlap. Addressing obesity is a post-acute phase activity in non-communicable disease management in humanitarian settings. Information is needed to inform guidelines and timing of interventions. The objective of this review was to explore the prevalence of overweight and obesity in populations directly affected by humanitarian crises; the cascade of care in these populations and perceptions of patients with overweight and obesity.MethodsLiterature searches were carried out in five databases. Grey literature was identified. The population of interest was non-pregnant, civilian adults who had experience of humanitarian crises (armed conflict, complex emergencies and natural disasters). All study types published from January 1st, 2011, were included. Screening, data extraction and quality appraisal were carried out in duplicate. A narrative synthesis is presented.ResultsFifty-six reports from forty-five studies were included. Prevalence estimates varied widely across the studies and by subgroups. Estimates of overweight and obesity combined ranged from 6.4% to 82.8%. Studies were heterogenous. Global distribution was skewed. Increasing adiposity was seen over time, in older adults and in women. Only six studies were at low risk of bias. Body mass index was the predominant measure used. There were no studies reporting cascade of care. No qualitative studies were identified.ConclusionOverweight and obesity varied in crisis affected populations but were rarely absent. Improved reporting of existing data could provide more accurate estimates. Worsening obesity may be prevented by acting earlier in long-term crises and targeting risk groups. The use of waist circumference would provide useful additional information. Gaps remain in understanding the existing cascade of care. Cultural norms around diet and ideal body size vary.

Large carnivores have long fascinated human societies and have profound influences on ecosystems. However, their conservation represents one of the greatest challenges of our time, particularly where attacks on humans occur. Where human recreational and/or livelihood activities overlap with large carnivore ranges, conflicts can become particularly serious. Two different scenarios are responsible for such overlap: In some regions of the world, increasing human populations lead to extended encroachment into large carnivore ranges, which are subject to increasing contraction, fragmentation, and degradation. In other regions, human and large carnivore populations are expanding, thus exacerbating conflicts, especially in those areas where these species were extirpated and are now returning. We thus face the problem of learning how to live with species that can pose serious threats to humans. We collected a total of 5,440 large carnivore (Felidae, Canidae, and Ursidae; 12 species) attacks worldwide between 1950 and 2019. The number of reported attacks increased over time, especially in lower-income countries. Most attacks (68%) resulted in human injuries, whereas 32% were fatal. Although attack scenarios varied greatly within and among species, as well as in different areas of the world, factors triggering large carnivore attacks on humans largely depend on the socioeconomic context, with people being at risk mainly during recreational activities in high-income countries and during livelihood activities in low-income countries. The specific combination of local socioeconomic and ecological factors is thus a risky mix triggering large carnivore attacks on humans, whose circumstances and frequencies cannot only be ascribed to the animal species. This also implies that effective measures to reduce large carnivore attacks must also consider the diverse local ecological and social contexts.

Abstract Introduction Current contouring guidelines for curative radiation therapy for muscle‐invasive bladder cancer (MIBC) recommend margins of 1.5–2.0 cm, applied to the clinical target volume (CTV). This study assessed whether the use of volumetric modulated arc therapy (VMAT), cone beam computed tomography (CBCT) and strict bladder preparation allowed for a reduced planning target volume (PTV) expansion, resulting in lower doses to surrounding organs at risk (OARs). Methods Daily CBCT images for 12 patients (382 scans total) were retrospectively reviewed against four potential PTV margins created on and exported with the reference CT scan. To form the PTVs, three isotropic expansions of 0.5, 1.0 and 1.5 cm were applied to the CTV, as well as an anisotropic expansion of 1.5 cm superiorly and 1.0 cm in all other dimensions. Following treatment completion, the CBCTs were visually assessed to determine the margins encapsulating the bladder. For retrospective planning purposes, the 1.0‐cm and anisotropic margins were compared with the previously recommended margins to determine differences in OAR doses. Results The 0.5‐, 1.0‐ and 1.5‐cm isotropic margins (IM) and the anisotropic margin (ANIM) covered the CTV in 46.1, 96.8, 100 and 100% of CBCTs retrospectively. Doses to OARs were significantly lower for the reduced margin plans for the small bowel, rectum and sigmoid. Conclusion Bladder planning target volumes may be safely reduced. We endorse a PTV margin of 1.0cm anteriorly, posteriorly and inferiorly with 1.0–1.5 cm superiorly for radical whole bladder cases using strict bladder preparation, VMAT and pretreatment CBCTs.

Chemical heterogeneities in Apollo sample 76535 constrain the magmatic cooling history of the lunar Mg-suite to

Abstract Background Patients with COVID‐19 display a broad spectrum of manifestations from asymptomatic to life‐threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. Methods We investigated a total of 137 APs infected with SARS‐CoV‐2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD‐, S1‐, SSA/Ro‐ and dsDNA‐specific IgG. Results While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection‐induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID‐19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. Conclusion Our results reveal an immune mechanism that controls SARS‐CoV‐2‐induced detrimental B cell responses and COVID‐19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development.

Urgent global research demands real-time dissemination of precise data. Wikidata, a collaborative and openly licensed knowledge graph available in RDF format, provides an ideal forum for exchanging structured data that can be verified and consolidated using validation schemas and bot edits. In this research article, we catalog an automatable task set necessary to assess and validate the portion of Wikidata relating to the COVID-19 epidemiology. These tasks assess statistical data and are implemented in SPARQL, a query language for semantic databases. We demonstrate the efficiency of our methods for evaluating structured non-relational information on COVID-19 in Wikidata, and its applicability in collaborative ontologies and knowledge graphs more broadly. We show the advantages and limitations of our proposed approach by comparing it to the features of other methods for the validation of linked web data as revealed by previous research.

We reviewed the multiplex PCR results of 20,127 respiratory specimens tested in a hospital setting from January 2014 to April 2023. The seasonal oscillation patterns of 17 respiratory viruses were studied. Compared with 2014–2019, a prominent drop in PCR positivity (from 64.46–69.21% to 17.29–29.89%, p < 0.001) and virus diversity was observed during the COVID-19 pandemic, with predominance of rhinovirus/enterovirus, sporadic spikes of parainfluenza viruses 3 and 4, respiratory syncytial virus and SARS-CoV-2, and rare detection of influenza viruses, metapneumovirus, adenovirus and coronaviruses. The suppressed viruses appeared to regain activity from the fourth quarter of 2022 when pandemic interventions had been gradually relaxed in Hong Kong. With the co-circulation of SARS-CoV-2 and seasonal respiratory viruses, surveillance of their activity and an in-depth understanding of the clinical outcomes will provide valuable insights for improved public health measures and reducing disease burden.

Photocatalytic reduction of carbon dioxide (CO2) into value-added carbon products is a promising strategy for dealing with carbon emission. Selected metal–organic frameworks (MOFs) have been shown promise in photocatalytic CO2 reduction owing to their photochemical activity and structural modularity. Here, we take advantage of displaceable nonstructural ligands on the nodes of a pyrene-based MOF, NU-1000, to graft a molecular catalyst, tetra(4-carboxyphenyl) porphyrin iron (III) chloride (Fe-TCPP). The pyrene linkers in the MOF absorb photons and transfer electrons to the porphyrin catalyst, resulting in a self-contained photocatalyst. The obtained Fe-TCPP@NU-1000 heterogeneous catalysts exhibit activity for CO2 photoreduction under illumination at 390 nm, with a TON for CO of 22 in 2 h. Molecular hydrogen is co-evolved. Leaching of the grafted catalyst from the MOF ultimately limits performance.

Transforming growth factor β (TGF-β) has been shown to promote tumor invasion and metastasis by activating the matrix metalloproteinases (MMPs); however, signaling mechanisms remain controversial and therapies targeting MMPs are still suboptimal. In the present study, we found that combined therapy with Asiatic acid (AA), a Smad7 agonist, and Naringenin (NG), a Smad3 inhibitor, effectively retrieved the balance between Smad3 and Smad7 signaling in the TGF-β-rich tumor microenvironment and thus significantly suppressed tumor invasion and metastasis in mouse models of melanoma and lung carcinoma. Mechanistically, we unraveled that Smad3 acted as a transcriptional activator of MMP2 and as a transcriptional suppressor of tissue inhibitors of metalloproteinase-2 (TIMP2) via binding to 5′ UTR of MMP2 and 3′ UTR of TIMP2, respectively. Treatment with NG inhibited Smad3-mediated MMP2 transcription while increasing TIMP, whereas treatment with AA enhanced Smad7 to suppress TGF-β/Smad3 signaling, as well as the activation of MMP2 by targeting the nuclear factor-κB (NF-κB)-membrane-type-1 MMP (MT1-MMP) axis. Therefore, the combination of AA and NG additively suppressed invasion and metastasis of melanoma and lung carcinoma by targeting TGF-β/Smad-dependent MMP2 transcription, post-translational activation, and function.

This work reports the effect of scaling up annular centrifugal contactors (ACCs) upon the residence time distribution and the efficiency of extraction of uranium. The experiments were carried out in a multi-scale ACC platform of three ACCs with rotor diameters of 12, 25, and 40 mm. To enable direct comparison across all three scales of ACC, the residence time distributions were acquired by injecting dye into the solvent phase at a constant relative volume related to the ACC liquid holdup. Across all scales and flowrates, there was little difference in residence time distribution (95%, and it improved further in larger rotor diameter ACCs.

One of the most significant environmental problems in the world is the massive release of dye wastewater from the dyeing industry. Therefore, the treatment of dyes effluents has received significant attention from researchers in recent years. Calcium peroxide (CP) from the group of alkaline earth metal peroxides acts as an oxidizing agent for the degradation of organic dyes in water. It is known that the commercially available CP has a relatively large particle size, which makes the reaction rate for pollution degradation relatively slow. Therefore, in this study, starch, a non-toxic, biodegradable and biocompatible biopolymer, was used as a stabilizer for synthesizing calcium peroxide nanoparticles (Starch@CPnps). The Starch@CPnps were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer–Emmet–Teller (BET), dynamic light scattering (DLS), thermogravimetric analysis (TGA), energy dispersive X-ray analysis (EDX) and scanning electron microscopy (SEM). The degradation of organic dyes, methylene blue (MB), using Starch@CPnps as a novel oxidant was studied using three different parameters: initial pH of the MB solution, calcium peroxide initial dosage and contact time. The degradation of the MB dye was carried out via a Fenton reaction, and the degradation efficiency of Starch@CPnps was successfully achieved up to 99%. This study shows that the potential application of starch as a stabilizer can reduce the size of the nanoparticles as it prevents the agglomeration of the nanoparticles during synthesis.

Summary: Background: SARS-CoV-2 Omicron variant evades immunity from past infection or vaccination and is associated with a greater risk of reinfection among recovered COVID-19 patients. We assessed the serum neutralizing antibody (NAb) activity against Omicron variant (Omicron NAb) among recovered COVID-19 patients with or without vaccination. Methods: In this prospective cohort study with 135 recovered COVID-19 patients, we determined the serum NAb titers against ancestral virus or variants using a live virus NAb assay. We used the receiver operating characteristic analysis to determine the optimal cutoff for a commercially-available surrogate NAb assay. Findings: Among recovered COVID-19 patients, the serum live virus geometric mean Omicron NAb titer was statistically significantly higher among BNT162b2 recipients compared to non-vaccinated individuals (85.4 vs 5.6,P

Abstract Background Young adulthood has become synonymous with the development of poor lifestyle behaviours associated with an increased risk of preventable chronic disease in later years. Interventions aiming to improve health behaviours may be more engaging and effective if they are targeted to males or females than interventions with a gender-neutral approach. This review will examine the outcome effectiveness of gender-targeted and gender-neutral interventions targeting nutrition, physical activity or overweight/obesity in young adults (17–35 years). Methods Six electronic databases were searched for randomised controlled trials (RCTs) published up to December 2019 that evaluated nutrition, physical activity and/or overweight/obesity interventions in young adults (17–35 years). An effective intervention was one where the change in one or more primary outcome was positive and statistically significantly different from baseline, compared with control, or if no control comparator, compared with another active intervention. Effectiveness of outcomes was compared between gender-targeted and gender-neutral studies. Results In total 21,582 manuscripts were identified and 107 RCTs were included; 30 gender-targeted studies (28%) and 77 gender-neutral (72%). Most gender-targeted studies were female targeted (n = 22, 73%). Primary outcome/s were adiposity (n = 36, 34%), nutrition (n = 29, 27%), physical activity (n = 28, 26%), or a combination of (n = 14, 14%). A greater proportion of gender-targeted than gender-neutral studies were effective in improving nutrition (n = 6, 100% and n = 17, 74% of studies respectively) and physical activity outcomes (n = 6, 86% and n = 14, 67% respectively), where as a greater proportion of gender-neutral studies were effective in improving adiposity outcomes (n = 13, 59% and n = 5, 36% respectively). None of these differences were statistically significant. Meta-analyses for weight found no significant differences between gender-targeted and gender-neutral studies for weight loss or weight gain prevention studies. Meta-analysis for fruit and vegetable intake demonstrated a significantly greater increase in intervention participants in gender-targeted studies of +158 g/day for > 3 months. Conclusions Although differences in outcome effectiveness were identified between gender-targeted and gender-neutral studies, these were not significantly different. This is likely due to an insufficient number of studies to detect a difference. The meta-analysis for fruit and vegetable intake findings should be interpreted with caution due to including only two gender-targeted studies. The findings collectively are suggestive of a potential difference requiring further investigation. To truly determine the effectiveness of gender-targeted interventions, well-designed RCTs comparing gender-targeted interventions with gender-neutral and control are needed. Registration This systematic review is a secondary analysis of studies included in a systematic review examining the effectiveness of interventions targeting nutrition, physical activity, or overweight/obesity in young adults, for which a predefined protocol was registered with PROSPERO (CRD42017075795).

Abstract Background Positive end-expiratory pressure (PEEP) is used to optimize oxygenation by preventing alveolar collapse. However, PEEP can potentially decrease cardiac output through cardiopulmonary interactions. The effect of PEEP on cardiac output during cardiopulmonary resuscitation (CPR) is not known. Methods This was a preclinical randomized, controlled, animal study conducted in an animal research facility on 25 Landrace-Yorkshire pigs. After inducing cardiac arrest, CPR was performed with LUCAS 3. During CPR, pigs were ventilated at a PEEP of 0, 5, 10, 15, 20 cmH2O (randomly determined via lottery) for 9 min. Cardiac output, obtained via ultrasound dilution, and PaO2 were measured, and oxygen delivery calculated for each PEEP. Results A mixed-effects repeated-measures analysis of variance was used to compare the baseline value adjusted mean cardiac output, PaO2, and oxygen delivery between PEEP groups. Least significant difference test was used to conduct pairwise comparisons between PEEP groups. To determine optimum PEEP, Gaussian mixture model was applied to the adjusted means of cardiac output and oxygen delivery. Increasing PEEP to 10 and higher resulted in significant declines in cardiac output. A PEEP of 15 and higher resulted in significant declines in oxygen delivery. As PEEP was increased from 0 to 20, PaO2 increased significantly. Gaussian mixture model identified the 0–5 PEEP group as providing optimal cardiac output and oxygen delivery, with PEEP of 5 providing the highest oxygen delivery. Conclusions A PEEP of 0–5 resulted in the optimal oxygen delivery and cardiac output during CPR, with PEEP of 5 resulting in higher oxygen delivery, and a slightly lower, statistically insignificant cardiac output than PEEP of 0.

Technology transfer for economic bulk production is the greatest challenge of the era. Production of high strength lightweight materials with nanocarbon reinforcement has attained its importance among the researchers. Property enhancement with multi-walled carbon nanotube (MWCNT) reinforcement is reported by all researchers. But effective utilization of its property remains a challenge even though it is the strongest material in the world. Achieving homogeneous dispersion especially in molten metal is a complex task. To address the same, a new approach was tried which could trigger de-bundling and make a uniform dispersion. Various metallurgical and mechanical characterizations were done. Grain refinement and the structure were studied with an optical microscope, MWCNT dispersion and structural damage was studied using field emission scanning microscope, Phase change and reactions during casting was done with XRD scan. The method remarkably facilitated 23.7% and 69.75% improvement in hardness and ultimate compressive strength respectively with the addition of MWCNT.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.

ObjectiveTo explore the perceptions and experiences of schizophrenia from patients, their care givers, health care providers, spiritual and traditional healers to develop a community-based intervention for improving treatment adherence for people with schizophrenia in Pakistan.MethodsThis qualitative study involved four focus group discussions (FGD) with a total of 26 participants: patients and carers (n = 5), primary care staff (n = 7), medical technicians (n = 8) and traditional and spiritual healers (n = 6). The participants were selected using purposive sampling method. FGDs were audio-recorded and transcribed. A thematic analysis was applied to the data set.ResultsThe themes identified were (i) Schizophrenia is not merely a biomedical problem: participants believed that poverty and an inferiority complex resulting from social disparity caused schizophrenia and contributed to non-adherence to medications; (ii) Spiritual healing goes hand in hand with the medical treatment: participants regarded spiritual and traditional treatment methods as an inherent part of schizophrenia patients' well-being and rehabilitation; (iii) Services for mental illness: mental health is not covered under primary health in a basic health unit: participants believed that the lack of services, training and necessary medication in primary care are major issues for treating schizophrenia in community; (iv) Barriers to community-based interventions: primary care staff believed that multiple pressures on staff, lack of incentives, non-availability of medication and lack of formal referral pathways resulted in disintegration of dealing with schizophrenia patients in primary care facilities.ConclusionThe study has identified a number of barriers and facilitators to developing and delivering a psychosocial intervention to support people living with schizophrenia in Pakistan. In particular, the importance of involving spiritual and traditional healers was highlighted by our diverse group of stakeholders.

Glyphosate (N-phosphonomethyl glycine) is a non-selective, broad-spectrum organophosphate herbicide. Its omnipresent application with large quantity has made glyphosate as a problematic contaminant in water. Therefore, an effective technology is urgently required to remove glyphosate and its metabolites from water. In this study, calcium peroxide nanoparticles (nCPs) were functioned as an oxidant to produce sufficient hydroxyl free radicals (·OH) with the presence of Fe2+ as a catalyst using a Fenton-based system. The nCPs with small particle size (40.88 nm) and high surface area (28.09 m2/g) were successfully synthesized via a co-precipitation method. The synthesized nCPs were characterized using transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), Brunauer–Emmett–Teller analysis (BET), dynamic light scattering (DLS), and field emission scanning electron microscopy (FESEM) techniques. Under the given conditions (pH = 3.0, initial nCPs dosage = 0.2 g, Ca2+/Fe2+ molar ratio = 6, the initial glyphosate concentration = 50 mg/L, RT), 99.60% total phosphorus (TP) removal and 75.10% chemical oxygen demand (COD) removal were achieved within 75 min. The degradation process fitted with the Behnajady–Modirshahla–Ghanbery (BMG) kinetics model. The H2O2 release performance and proposed degradation pathways were also reported. The results demonstrated that calcium peroxide nanoparticles are an efficient oxidant for glyphosate removal from aqueous systems.

Introduction: The transition from pediatric health care and school systems presents enormous challenges for young adults with cerebral palsy (CP). The lack of strong societal support during this seminal life event is well-documented and leads many adults with CP to struggle with independence, higher education, and employment. Despite the relatively high prevalence of CP, information about the experiences and function of adults with CP in our society continues to be limited. The purpose of this project was to describe well-being by assessing education, employment, physical function, walking activity, and utilization of health care in an ambulatory adult cohort with CP who received specialized pediatric care at our center.Method: In this Institutional Review Board-approved prospective study, we invited former patients from our tertiary care pediatric CP center to complete a set of patient-reported outcomes including (1) the Patient-Reported Outcomes Measurement Information System domains of physical function and pain interference, (2) the Satisfaction with Life Scale, and a project-specific demographic questionnaire about education, employment, income, independence, pain, and health care utilization. Participants also wore a pedometer for 8 days to monitor community walking activity. Chi-squared pairwise or t-tests were used as appropriate to compare survey responses and walking activity data between three groups: participants who self-reported, those who reported by proxy, and published normative data from age-matched typically developing adult (TDA) samples.Results: One hundred twenty-six adults with CP consented to participate; 85 self-reported [age 29.7 ± 4.3 years; Gross Motor Function Classification System: I (28%), II (47%), and III, (25%)] and 41 reported by proxy [age 29.7 ± 4.1 years; Gross Motor Function Classification System: I (10%), II (68%), and III (22%)]. For the group who self-reported, high school graduation rate (99%) was similar to TDA (92%; p = 0.0173) but bachelor's degree achievement rate (55%) was higher than TDA (37%; p < 0.001). Despite more advanced education, the unemployment rate in this group was higher than national levels at 33% and was associated with high utilization of Social Security Disability Insurance (33%). Within the self-reporting group, 13% required a caregiver. For the group who reported by proxy, educational levels (73% high school graduates, 0 bachelor's degree) were lower than the general population (p < 0.001) and unemployment was higher than the national level, at 64%. Unemployment in this group was associated with high utilization of Social Security Disability Insurance (85%). Within the proxy-reporting group, 71% required a caregiver. The full cohort demonstrated lower levels of physical function according to the Patient-Reported Outcomes Measurement Information System and less community walking activity compared with TDA references (p < 0.001). This cohort of adults with CP reported significantly higher frequency of chronic pain (48 vs. 12% for TDA; p < 0.001), but less pain interference with daily activities than TDA based on Patient-Reported Outcomes Measurement Information System results (p < 0.001). This cohort reported good to excellent overall health (93%) and high utilization of primary care (98%), but limited utilization of specialty care, specifically orthopedic care (21%) and physical therapy (15%).Discussion: This cohort of adults with CP had similar levels of education as the general population, but had relatively high rates of unemployment, caretaker need, and Social Security Disability Insurance utilization. Although chronic pain was frequent, the impact of pain on work and independent living did not exceed reports from a typically developing reference. Better targeted societal resources for adults with physical disabilities are urgently needed to allow equitable access to employment, promote opportunities for independence, and enable full participation in community life.

HIV envelope glycoprotein is the most heavily glycosylated viral protein complex identified with over 20 glycans on its surface. This glycan canopy is thought to primarily shield the virus from host immune recognition as glycans are poor immunogens in general, however rare HIV neutralizing antibodies nevertheless potently recognize the glycan epitopes. While CD4 and chemokine receptors have been known as viral entry receptor and coreceptor, for many years the role of viral glycans in HIV entry was controversial. Recently, we showed that HIV envelope glycan binds to L-selectin in solution and on CD4 T lymphocytes. The viral glycan and L-selectin interaction functions to facilitate the viral adhesion and entry. Upon entry, infected CD4 T lymphocytes are stimulated to progressively shed L-selectin and suppressing this lectin receptor shedding greatly reduced HIV viral release and caused aggregation of diminutive virus-like particles within experimental infections and from infected primary T lymphocytes derived from both viremic and aviremic individuals. As shedding of L-selectin is mediated by ADAM metalloproteinases downstream of host-cell stimulation, these findings showed a novel mechanism for HIV viral release and offer a potential new class of anti-HIV compounds.

This article explores the author’s ‘personal manifesto’. It describes the framework he devised to help him understand his style, preferences and needs in a professional context and explores the intersection of the professional and the personal, identifying links between how we think and act in the professional context and in our wider lives as individuals. The manifesto grew out of the opportunities presented by starting a new role and was formulated through making sense of the new thinking, reflection and ideas prompted by that experience. It explores a variety of themes personal to the author, such as the importance of being intellectually engaged in the professional context, the value of positivity, innovation and ambitious thinking, and the importance of positive relationships with others built around emotional intelligence.

Nanoscale calcium peroxide (nCP) has turned out to be one of the effective and environmentally friendly approaches for wastewater remediation purposes. The rapid hydrolysis of nCPs and burst oxygen release caused by the high surface-to-volume ratio of nCPs could surpass the appropriate demand for oxygenation and pollutant degradation in the aqueous system. Thus, coated oxidants (COs) have been prepared using polymeric materials to ensure long-term efficacy and slow-release capability. Therefore, the nCPs were first prepared using dextran as a stabilizer to prevent irreversible agglomeration by the chemical precipitation method and had an average mean size of 2.33 ± 0.81 nm. The synthesized nCPs were then coated with dextran to produce dextran-coated nCPs. Their characteristics and effectiveness in doxycycline (DOX) degradation were assessed. The characterization of nCPs and dextran-coated nCPs was performed using X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), fourier transform infrared spectroscopy (FTIR), Brunauer, Emmett and Teller analysis (BET), dynamic light scattering (DLS) and thermogravimetric analysis (TGA) techniques. This work suggests that dextran-coated nCPs are beneficial in wastewater treatment practice in terms of the long-term efficacy of DOX degradation potential.