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Background The advantages of segmentectomy over lobectomy in sparing pulmonary function remain controversial. Lower lobe segmentectomy is divided into simple segmentectomy, such as segment 6; and complex segmentectomy that includes the basal segments. Here, we compared residual lung function after thoracoscopic segmentectomy versus lobectomy in the lower lobe using the three-dimensional computed tomography volumetric method. Methods Between January 2012 and October 2020, 67 patients who underwent thoracoscopic segmentectomy of the lower lobe were matched to 67 patients who underwent thoracoscopic lower lobectomy during the same period using propensity score matching analysis. The postoperative decrease in the rate of forced expiratory volume in 1 s was compared between methods. The regional forced expiratory volume in 1 s of the residual lobe rescued by segmentectomy was measured using volumetric and spirometric analyses and compared to lower lobectomy. The ratio of the actual to predicted postoperative forced expiratory volume in 1 s in the residual lobe was defined as the preservation rate. Results Of the 67 thoracoscopic segmentectomies, 43 were S6, seven were S8, three were S8 + 9, seven were S10, and seven were S9 + 10. The percentage of postoperative/preoperative forced expiratory volume in 1 s was significantly higher in the segmentectomy versus lobectomy group (90.7% vs. 85.7%, p = 0.001). The preservation rates after simple segmentectomy ( n = 43) and complex segmentectomy ( n = 24) did not differ significantly (82.2% vs. 80.2%, p = 0.709). Conclusions Thoracoscopic lower lobe segmentectomy versus lobectomy preserves postoperative lung function. Even complex segmentectomy exhibited outcomes relevant to simple segmentectomy by sparing the residual lobe.

Solar cell layers technology has achieved global standing in the solar cell layers deposition process, and it covers the innovative methods and techniques in significant applications. Recent solar cell layers technology has an advanced interest in a refined approach to enhance performance and highlights the importance of recent proficient procedures for manufacturing. For example, the application is used to search for novel materials for solar cells' layers to clarify the current energy crisis. The technological process and various types of solar cells depend on climate change. Among them, layers of solar cells and silicon wafer solar cells are very encouraging. Solar cell layers technology has led to solar cells being a more reasonable active option in design and production. The productivities facilitated by new solar cells still need to be enhanced for the various processes involved in the additional enhancement from Copper Indium Gallium Selenide (CIGS) microfilms to solar cell crystal structure dye-sensitized solar cells. The hydrophobic coating works as an anti-dust coating, enhancing efficiency and decreasing the cost of cleaning solar cells. In Saudi Arabia Majmaah City, most solar projects are in dry regions, where the dusty weather reduces solar cell efficiency. Therefore, combining these two properties and applying an anti-reflective and superhydrophobic coating will increase solar cell efficiency by 20%. Solar cells' crystal structure results are substituted with layers or new materials to balance environmental impact and toxic nature.

In this study, using a new polymer combination of Chitosan(CH)/Xanthan Gum(XG) has been exhibited for wound dressing implementation by the 3D-Printing method, which was fabricated due to its biocompatible, biodegradable, improved mechanical strength, low degradation rate, and hydrophilic nature to develop cell-mimicking, cell adhesion, proliferation, and differentiation. Different concentrations of XG were added to the CH solution as 0.25, 0.50, 0.75, 1, and 2 wt% respectively in the formic acid/distilled water (1.5:8.5) solution and rheologically characterized to evaluate their printability. The results demonstrated that high mechanical strength, hydrophilic properties, and slow degradation rate were observed with the presence and increment of XG concentration within the 3D-Printed patches. Moreover, in vitro cell culture research was conducted by seeding NIH 3T3 fibroblast cells on the patches, proving the cell proliferation rate, viability, and adhesion. Finally, 1% XG and 4% CH containing 3D-Printed patches were great potential for wound dressing applications.

Introduction Access to surgical service is limited by provider availability and geographic barriers. Telemedicine ensures that patients can access medical care. Objective The objective is to describe our use of telemedicine in delivering vascular surgery services to remote locations before and during the COVID-19 pandemic. Methods We conducted a retrospective chart review analyzing care delivered at six vascular surgery telemedicine clinics over a 22-month period. We examined vascular diagnoses, recommended interventions, referrals placed, and emergency department visits within 30 days of evaluation. We calculated travel distance saved for patients between their local clinic and our main hospital. Results We identified 94 patients and 144 telemedicine visits, with an average of 1.5 visits per patient (SD = 0.73). The most common referrals were for peripheral artery disease (20.2%) and abdominal aortic aneurysm (14.9%). Three patients were immediately referred to the emergency department due to concern for acute limb ischemia (2) or questionable symptomatic AAA (1). Telemedicine visit recommendations were distributed between no intervention (n = 30, 31.9%), medical management (n = 41, 43.6%), and surgical intervention (n = 23, 24.5%). The surgical intervention cohort was most commonly referred to arterial revascularization (n = 4), venous ablation (n = 4), and arteriovenous fistula procedures (n = 4). Fourteen patients came to our main hospital for surgery and four to local providers. Average travel distance saved per telemedicine visit was 104 miles (SD = 43.7). Conclusions Telemedicine provided safe, efficient care during the COVID-19 pandemic and saved patients an average of 104 travel miles per visit.

Cell layers eliminate unwanted cells through the extrusion process, which underlines healthy versus flawed tissue behaviors. Although several biochemical pathways have been identified, the underlying mechanical basis including the forces involved in cellular extrusion remains largely unexplored. Utilizing a phase-field model of a three-dimensional cell layer, we study the interplay of cell extrusion with cell–cell and cell–substrate interactions in a flat monolayer. Independent tuning of cell–cell versus cell–substrate adhesion forces reveals that extrusion events can be distinctly linked to defects in nematic and hexatic orders associated with cellular arrangements. Specifically, we show that by increasing relative cell–cell adhesion forces the cell monolayer can switch between the collective tendency towards fivefold, hexatic, disclinations relative to half-integer, nematic, defects for extruding a cell. We unify our findings by accessing three-dimensional mechanical stress fields to show that an extrusion event acts as a mechanism to relieve localized stress concentration.

Salmonella enterica serovar Enteritidis is one of the most frequent causes of Salmonellosis globally and is commonly transmitted from animals to humans by the consumption of contaminated foodstuffs. In the UK and many other countries in the Global North, a significant proportion of cases are caused by the consumption of imported food products or contracted during foreign travel, therefore, making the rapid identification of the geographical source of new infections a requirement for robust public health outbreak investigations. Herein, we detail the development and application of a hierarchical machine learning model to rapidly identify and trace the geographical source of S. Enteritidis infections from whole genome sequencing data. 2313 S. Enteritidis genomes, collected by the UKHSA between 2014–2019, were used to train a ‘local classifier per node’ hierarchical classifier to attribute isolates to four continents, 11 sub-regions, and 38 countries (53 classes). The highest classification accuracy was achieved at the continental level followed by the sub-regional and country levels (macro F1: 0.954, 0.718, 0.661, respectively). A number of countries commonly visited by UK travelers were predicted with high accuracy (hF1: >0.9). Longitudinal analysis and validation with publicly accessible international samples indicated that predictions were robust to prospective external datasets. The hierarchical machine learning framework provided granular geographical source prediction directly from sequencing reads in

Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and an important cause of childhood mortality. Despite the introduction of successful vaccines, the global spread of both non-vaccine serotypes and antibiotic-resistant strains reinforce the development of alternative therapies against this pathogen. One possible route is the development of monoclonal antibodies (mAbs) that induce killing of bacteria via the immune system. Here we investigate whether mAbs can be used to induce killing of pneumococcal serotypes for which the current vaccines show unsuccessful protection. Our study demonstrates that when human mAbs against pneumococcal capsule polysaccharides (CPS) have a poor capacity to induce complement activation, a critical process for immune protection against pneumococci, their activity can be strongly improved by hexamerization-enhancing mutations. Our data indicate that anti-capsular antibodies may have a low capacity to form higher-order oligomers (IgG hexamers) that are needed to recruit complement component C1. Indeed, specific point mutations in the IgG-Fc domain that strengthen hexamerization strongly enhance C1 recruitment and downstream complement activation on encapsulated pneumococci. Specifically, hexamerization-enhancing mutations E430G or E345K in CPS6-IgG strongly potentiate complement activation on S. pneumoniae strains that express capsular serotype 6 (CPS6), and the highly invasive serotype 19A strain. Furthermore, these mutations improve complement activation via mAbs recognizing CPS3 and CPS8 strains. Importantly, hexamer-enhancing mutations enable mAbs to induce strong phagocytosis and intracellular killing by human neutrophils. Finally, passive immunization with CPS6-IgG1-E345K protected mice from developing severe pneumonia. Altogether, this work provides an important proof-of-concept for future optimization of antibody therapies against encapsulated bacteria.

Peer reviewed: True, Acknowledgements: With thanks to Dr Kate Criswell and Dr Christine Hirschberger for advice, and to the University of Cambridge Wellcome PhD. Programme in Developmental Mechanisms. The authors were funded by a Wellcome PhD studentship (214953/Z/18/Z) to JMR, and by a Royal Society University Research Fellowship (UF130182 and URF\R\191007) and Royal Society Research Grant (RG140377) to JAG., The gill skeleton of cartilaginous fishes (sharks, skates, rays, and holocephalans) exhibits a striking anterior–posterior polarity, with a series of fine appendages called branchial rays projecting from the posterior margin of the gill arch cartilages. We previously demonstrated in the skate (Leucoraja erinacea) that branchial rays derive from a posterior domain of pharyngeal arch mesenchyme that is responsive to Sonic hedgehog (Shh) signaling from a distal gill arch epithelial ridge (GAER) signaling centre. However, how branchial ray progenitors are specified exclusively within posterior gill arch mesenchyme is not known. Here, we show that genes encoding several Wnt ligands are expressed in the ectoderm immediately adjacent to the skate GAER, and that these Wnt signals are transduced largely in the anterior arch environment. Using pharmacological manipulation, we show that inhibition of Wnt signalling results in an anterior expansion of Shh signal transduction in developing skate gill arches, and in the formation of ectopic anterior branchial ray cartilages. Our findings demonstrate that ectodermal Wnt signalling contributes to gill arch skeletal polarity in skate by restricting Shh signal transduction and chondrogenesis to the posterior arch environment and highlights the importance of signalling interactions at embryonic tissue boundaries for cell fate determination in vertebrate pharyngeal arches.

Abstract: Cancer is fundamentally a disease of perturbed genes. Although many mutations can be marked in the genome of cancer or a transformed cell, the initiation and progression are driven by only a few mutational events, viz., driver mutations that progressively govern and execute the functional impacts. The driver mutations are thus believed to dictate and dysregulate the subsequent cellular proliferative function/decisions, thereby producing a cancerous state. Therefore, identifying the driver events from the genomic alterations in a patient’s cancer cell gained enormous attention recently for designing better targeting therapies and paving the way for precision cancer medicine. With rolling advancements in high-throughput omic technologies, analysis of genetic variations and gene expression profiles for cancer patients has become a routine clinical practice. However, it is anticipated that protein structural alterations resulting from such driver mutations can provide more direct and clinically relevant evidence of disease states than genetic signatures alone. This review comprehensively discusses various aspects and approaches that have been developed for the prediction of cancer drivers using genetic signatures and protein structures and their potential application in developing precision cancer therapies.

This paper presents quantitative research results regarding the influence of demographic factors on the earthquake risk perception of the citizens of Belgrade. This research aims to determine how much the citizens of Belgrade are aware of the risk and prepared to react in the event of an earthquake. The relationship between gender, age, level of education, and facility ownership with risk perception was examined. T-test, One-way ANOVA, and Pearson correlation coefficient were used to examine the relationship between the variables and the earthquake risk perception. The survey was conducted using a questionnaire that was given and then collected online among 235 Belgrade respondents during September 2020. The questions were divided into three categories. The first part of the questionnaire was consisted of general questions about the demographic characteristics of the respondents, then the questions that would determine the level of awareness of the respondents about earthquakes, and finally, the questions for determining the respondents' preparedness. The results of the research show that women have a higher perception of risk. It has been proven that the youngest respondents from the age category of 18-30 have the lowest risk perception. The influence of education level in no case showed a statistically significant correlation with risk perception.

This paper responds to the research question, “can urban farming in Nepal help create sustainable cities?” Especially after the COVID-19 pandemic, urban residents have begun to realize that food transported from long distances is not always reliable. Urban farming can help produce fresh food locally and help urban residents become self-reliant by engaging in healthy eating habits and practicing sustainable agricultural techniques in food-desert areas, while creating a positive impact on the environment through regenerative agricultural methods. In doing so, urban farms can help the growers save on food expenditures and even earn some additional income, while also improving air quality and minimizing the effects of urban heat islands. This practice also helps reduce greenhouse gases through plant carbon use efficiency (CUE), as vegetation carbon dynamics (VCD) can be adjusted while supporting the circular economy. As urban lands command higher prices than agricultural land, urban farming usually happens on residential yards, roofs, balconies, community gardens, and dedicated areas in public parks. Rainwater harvesting and redirecting can help irrigate urban farms, which can be part of rain gardens. The national census of 2021 identified that 66% of Nepal’s population lives in urban areas. However, the World Bank (2018) showed that only 21 of Nepal’s population was projected to live in urban areas in 2021. It is not debatable that the urbanization process in Nepal is on the rise. Thus, urban agriculture can play an important role in supplementing residents’ food needs. Many cities in Nepal have already successfully adapted to urban farming wherein residents grow food on their building sites, balconies, and rooftop, often growing plants in pots, vases, and other types of containers. The UN-Habitat, with the support of the European Union and local agencies, published a rooftop farming training manual (2014), showing the feasibility of urban farming in Nepal. This paper discusses how public-private partnership (PPP) can promote urban agriculture and make the process more effective and attractive to urban-farming households. It also analyzes how a PPP approach also facilitates the use of better technology, advisory support, and use of research extension activities. This paper draws on a literature review, uses remote-sensing imagery data and data from National Census Nepal 2021, and the authors’ professional experiences related to best practices in the areas to analyze the benefits and challenges related to urban farming both in Nepal and Arizona, USA. The paper provides recommendations for Nepali cities to maximize the benefit provided by urban farming. It is expected to be useful to Nepali policymakers, government agencies, and nonprofit organizations which promote sustainability, and organic farming with a sustainable supply chain.

© 2023 International Union of Biochemistry and Molecular Biology, Inc.Antiproliferative activity of Achillea vermicularis extracts was calculated on glial (C6) and keratinocyte (HaCaT) cell lines using XTT assay. It was observed that all extracts of A. vermicularis at the determined concentration were not cytotoxic in HaCaT cell lines. The nanoparticles (NPs) of the extract with the best cytotoxic activity was prepared, and necessary characterization studies were performed. Results showed that NP containing the extract has a lower IC50 value and more cytotoxic activity in C6 cells compared to the only extract. Furthermore, the antiepileptic potentials of these substances were explored in this study. The effect of A. vermicularis extracts on the enzyme activities of carbonic anhydrase I and II isoenzymes (hCA I and hCA II) was measured using spectrophotometry to achieve this goal. A. vermicularis extracts demonstrated high inhibitory activities compared to standard inhibitor (acetazolamide, AAZ), with IC50 values in the range of 5.04–10.8 μg/ml for hCA I, and 5.40–9.22 μg/ml for hCA II. High-performance liquid chromatography diode array detector (HPLC-DAD) was used in this investigation to assess the main chemicals found in the extract and NPs. The results showed that the ethanol extract (157.636 μg/mg extract) and NPs (4.631 μg/mg extract) had a significant amount of the 8-hydroxy salvigenin component.

Problem: The novel coronavirus disease 2019 (COVID-19) pandemic adversely affected the preparation of Malaysia’s National Health and Morbidity Survey for 2020 because conducting it would expose data collectors and participants to an increased risk of infection. Context: The survey is nationally representative and community based and is conducted by the Institute for Public Health, part of the National Institutes of Health, to generate health-related evidence and to support the Malaysian Ministry of Health in policymaking. Its planned scope for 2020 was the seroprevalence of communicable diseases such as hepatitis B and C. Action: Additional components were added to the survey to increase its usefulness, including COVID-19 seroprevalence and facial anthropometric studies to ensure respirator fit. The survey’s scale was reduced, and data collection was changed from including only face-to-face interviews to mainly self-administered and telephone interviews. The transmission risk to participants was reduced by screening data collectors before the survey and fortnightly thereafter, using standard droplet and contact precautions, ensuring proper training and monitoring of data collectors, and implementing other administrative infection prevention measures. Outcome: Data were collected from 7 August to 11 October 2020, with 5957 participants recruited. Only 4 out of 12 components of the survey were conducted via face-to-face interview. No COVID-19 cases were reported among data collectors and participants. All participants were given their hepatitis and COVID-19 laboratory test results; 73 participants with hepatitis B and 14 with hepatitis C who had been previously undiagnosed were referred for further case management. Discussion: Preparing and conducting the National Health and Morbidity Survey during the COVID-19 pandemic required careful consideration of the risks and benefits, multiple infection prevention measures, strong leadership and strong stakeholder support to ensure there were no adverse events.

Background: Leprosy elimination was achieved in the Western Pacific Region of the World Health Organization (WHO) in the late 1980s. However, cases continue to be reported within the Region. This paper analyses leprosy cases in the Region reported to WHO during 1991–2019. Methods: Descriptive analyses were conducted of data from leprosy surveillance reported in the Region. Key indicators included prevalence, the number and rate of new cases detected, proportions of cases with multibacillary leprosy or grade 2 disability, and the numbers and proportions of cases among children and cases by sex. Results: From 1991 to 2019, the number of registered cases detected in the Region decreased by 94% (from 68 313 in 1991 to 4381 in 2019), and the number of new cases detected decreased by 72.1% (from 15 002 in 1991 to 4004 in 2019). The proportion of cases of multibacillary leprosy increased from 67.4% (8045/11 943) in 1995 to 85.6% (3428/4004) in 2019, and between 1997 and 2019 the number of leprosy cases occurring in children decreased from 1240 to 424. The proportion of new cases with grade 2 disability decreased from 15.4% in 1997 to 6.6% in 2019. With few exceptions, nearly two thirds of reported cases occurred in males. Conclusion: Most countries and areas in the Region have successfully eliminated leprosy, although some pockets remain in countries with hard-to-reach areas. The introduction of multidrug therapy and WHO’s 1991 elimination goals may have prompted the initial decline in leprosy cases. Continued efforts are required in case-finding, care and prevention in areas with a high burden of disease.

Adolescent’s access to quality Sexual and Reproductive Health and Rights interventions has been a major issue in most of the low- to middle-income countries (LMICs) across the globe. This systematic review aims to identify the relevant community and school-based interventions that can be implemented in -LMICs to promote adolescent’s sexual and reproductive health and rights outcomes. We identified 54 studies and our review findings suggest that Adolescent’s Sexual and Reproductive Health and Rights (ASRHR) educational interventions, provision of financial incentives, and provision of comprehensive -post-abortion family planning services are effective in increasing adolescent’s knowledge on ASRHR, attitude towards ASRHR, uptake of ASRHR services, contraception and decreased unwanted pregnancy rates among young women. However, we found inconclusive and limited evidence on the effectiveness of the interventions to improve violence prevention and adolescent behaviors towards safe sexual practices. More rigorous studies with long-term follow-ups are needed to assess the effectiveness of such interventions.

Peer reviewed: True, Pathogens utilize a panoply of effectors to manipulate plant defense. However, despite their importance, relatively little is actually known about regulation of these virulence factors. Here, we show that the effector Fol-Secreted Virulence-related Protein1 (FolSvp1), secreted from fungal pathogen Fusarium oxysporum f. sp. lycopersici (Fol), directly binds and translocates the tomato pathogenesis-related protein1, SlPR1, from the apoplast outside the plasma membrane to the host nucleus via its nuclear localization signal. Relocation of SlPR1 abolishes generation of the defense signaling peptide, CAPE1, from its C-terminus, and as a consequence, facilitates pathogen invasion of plants. The action of FolSvp1 requires covalent modification by acetylation for full virulence in host tomato tissues. The modification is catalyzed by the Fol FolArd1 lysine acetyltransferase prior to secretion. Addition of an acetyl group to one residue, K167, prevents ubiquitination-dependent degradation of FolSvp1 in both Fol and plant cells with different mechanisms, allowing it to function normally in fungal invasion. Either inactivation of FolSvp1 or removal of the acetyl group on K167 leads to impaired pathogenicity of Fol. These findings indicate that acetylation can regulate the stability of effectors of fungal plant pathogens with impact on virulence.

During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To do so, k-fibers must be robustly anchored to the dynamic spindle. We previously developed microneedle manipulation to mechanically challenge k-fiber anchorage, and observed spatially distinct response features revealing the presence of heterogeneous anchorage (Suresh et al. 2020). How anchorage is precisely spatially regulated, and what forces are necessary and sufficient to recapitulate the k-fiber’s response to force remain unclear. Here, we develop a coarse-grained k-fiber model and combine with manipulation experiments to infer underlying anchorage using shape analysis. By systematically testing different anchorage schemes, we find that forces solely at k-fiber ends are sufficient to recapitulate unmanipulated k-fiber shapes, but not manipulated ones for which lateral anchorage over a 3 μm length scale near chromosomes is also essential. Such anchorage robustly preserves k-fiber orientation near chromosomes while allowing pivoting around poles. Anchorage over a shorter length scale cannot robustly restrict pivoting near chromosomes, while anchorage throughout the spindle obstructs pivoting at poles. Together, this work reveals how spatially regulated anchorage gives rise to spatially distinct mechanics in the mammalian spindle, which we propose are key for function.

Abstract: Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46–68.76 µM, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 µM. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment. Graphical abstract: [Figure not available: see fulltext.].

Biological rhythms are ubiquitous. They can be generated by circadian oscillators, which produce daily rhythms in physiology and behavior, as well as by developmental oscillators such as the segmentation clock, which periodically produces modular developmental units. Here, we show that the circadian clock controls the timing of late-stage floret development, or anthesis, in domesticated sunflowers. In these plants, up to thousands of individual florets are tightly packed onto a capitulum disk. While early floret development occurs continuously across capitula to generate iconic spiral phyllotaxy, during anthesis floret development occurs in discrete ring-like pseudowhorls with up to hundreds of florets undergoing simultaneous maturation. We demonstrate circadian regulation of floral organ growth and show that the effects of light on this process are time-of-day dependent. Delays in the phase of floral anthesis delay morning visits by pollinators, while disruption of circadian rhythms in floral organ development causes loss of pseudowhorl formation and large reductions in pollinator visits. We therefore show that the sunflower circadian clock acts in concert with environmental response pathways to tightly synchronize the anthesis of hundreds of florets each day, generating spatial patterns on the developing capitulum disk. This coordinated mass release of floral rewards at predictable times of day likely promotes pollinator visits and plant reproductive success.

Objective:This study was conducted to evaluate the persisting Covid-19-related symptoms of the cases included in our study and to assess their cardiac findings to determine the impact of Covid-19 on children’s cardiovascular health.Methods:In this study, 121 children between the ages of 0– and 18 with Covid-19 were evaluated based on their history, blood pressure values, and electrocardiography and echocardiography results. These findings were compared with the findings of the control group which consisted of 95 healthy cases who were in the same age range as the study group and did not have Covid-19. The results were evaluated using the statistics program, SPSS 21.Results:There was no significant difference between the study group and the control group in terms of age, weight, and body mass index. The clinical symptoms (chest and back pain, dizziness, headache, palpitation, fatigue, shortness of breath, loss of balance, coughing) of 37.2% of the cases persisted for at least 1 month after Covid-19 recovery. Statistically significant differences were found in systolic blood pressure, left ventricular ejection fraction, relative wall thickness, and tricuspid annular plane systolic excursion.Conclusion:The continuation of some cases’ clinical symptoms post-recovery indicates that long Covid infection can be observed in children. The fact that statistically significant differences were observed between the echocardiographic parameters of the study and control groups suggests that Covid-19 may have effects on the cardiovascular system. To shed light on the long Covid cases among children and the infection’s cardiac impacts, it would be beneficial to conduct more comprehensive studies on this matter.

Background:Coronavirus disease 2019 (COVID-19) is responsible for significant lung disease in adults. Despite mild manifestations in most children, multisystem inflammatory syndrome (MIS-C) associated with COVID-19 is well described in older children with cardiac manifestations. However, MIS-C-related cardiac manifestations are not as well described in younger children.Methods:The study is a retrospective analysis of MIS-C patients under the age of 5 years admitted between May and November 2020 to a single centre. Included cases fulfilled the case definition of MIS-C according to Royal College of Pediatrics and Child Health criteria with laboratory, electrocardiogram, or echocardiographic evidence of cardiac disease. Collected data included patients’ demographics, laboratory results, echocardiographic findings, management, and outcomes.Results:Out of 16 MIS-C cases under 5 years of age, 10 (62.5%) had cardiac manifestations with a median age of 12 months, 9 (90%) were previously healthy. Cardiac manifestations included coronary arterial aneurysms or ectasia in five (50%) cases, two (20%) with isolated myopericarditis, coronary ectasia with myocarditis in two (20%), and supraventricular tachycardia in one (10%). Intravenous immunoglobulins were given in all cases with coronary involvement or myocarditis. The median duration of hospitalisation was 7 (6–14) days; two (20%) cases with cardiac disease were mechanically ventilated and mortality in MIS-C cases below 5 years was 12.5%. Normalisation of systolic function occurred in half of the affected cases within 1 week and reached 100% by 30 days of follow-up.Conclusions:MIS-C associated with SARS-CoV-2 has a high possibility of serious associated cardiac manifestations in children under the age of 5 years with mortality and/or long-term morbidities such as coronary aneurysms even in previously healthy children.

Staphylococcus epidermidis causes some of the most hard-to-treat clinical infections by forming biofilms: Multicellular communities of bacteria encased in a protective matrix, supporting immune evasion and tolerance against antibiotics. Biofilms occur most commonly on medical implants, and a key event in implant colonization is the robust adherence to the surface, facilitated by interactions between bacterial surface proteins and host matrix components. S. epidermidis is equipped with a giant adhesive protein, extracellular matrix-binding protein (Embp), which facilitates bacterial interactions with surface-deposited, but not soluble fibronectin. The structural basis behind this selective binding process has remained obscure. Using a suite of single-cell and single-molecule analysis techniques, we show that S. epidermidis is capable of such distinction because Embp binds specifically to fibrillated fibronectin on surfaces, while ignoring globular fibronectin in solution. S. epidermidis adherence is critically dependent on multivalent interactions involving 50 fibronectin-binding repeats of Embp. This unusual, Velcro-like interaction proved critical for colonization of surfaces under high flow, making this newly identified attachment mechanism particularly relevant for colonization of intravascular devices, such as prosthetic heart valves or vascular grafts. Other biofilm-forming pathogens, such as Staphylococcus aureus, express homologs of Embp and likely deploy the same mechanism for surface colonization. Our results may open for a novel direction in efforts to combat devastating, biofilm-associated infections, as the development of implant materials that steer the conformation of adsorbed proteins is a much more manageable task than avoiding protein adsorption altogether.

A combined strategy of computational, protein engineering and cross-linked enzyme aggregates (CLEAs) approaches was performed on Bacillus lehensis G1 maltogenic amylase (Mag1) to investigate the preferred amino acids and orientation of the cross-linker in constructing stable and efficient biocatalyst. From the computational analysis, Mag1 exhibited the highest binding affinity towards chitosan (-7.5 kcal/mol) and favours having interactions with aspartic acid whereas glutaraldehyde was the least favoured (-3.4 kcal/mol) and has preferences for lysine. A total of eight Mag1 variants were constructed with either Asp or Lys substitutions on different secondary structures surface. Mutant Mag1-mDh exhibited the highest recovery activity (82.3%) in comparison to other Mag1 variants. Mutants-CLEAs exhibited higher thermal stability (20-30% activity) at 80 °C whilst Mag1-CLEAs could only retain 9% of activity at the same temperature. Reusability analysis revealed that mutants-CLEAs can be recovered up to 8 cycles whereas Mag1-CLEAs activity could only be retained for up to 6 cycles. Thus, it is evident that amino acids on the enzyme's surface play a crucial role in the construction of highly stable, efficient and recyclable CLEAs. This demonstrates the necessity to determine the preferential amino acid by the cross-linkers in advance to facilitate CLEAs immobilisation for designing efficient biocatalysts.

Biofilms, bacterial communities of cells encased by a self-produced matrix, exhibit a variety of three-dimensional structures. Specifically, channel networks formed within the bulk of the biofilm have been identified to play an important role in the colonies' viability by promoting the transport of nutrients and chemicals. Here, we study channel formation and focus on the role of the adhesion of the biofilm matrix to the substrate in Pseudomonas aeruginosa biofilms grown under constant flow in microfluidic channels. We perform phase contrast and confocal laser scanning microscopy to examine the development of the biofilm structure as a function of the substrates' surface energy. The formation of the wrinkles and folds is triggered by a mechanical buckling instability, controlled by biofilm growth rate and the film's adhesion to the substrate. The three-dimensional folding gives rise to hollow channels that rapidly increase the effective volume occupied by the biofilm and facilitate bacterial movement inside them. The experiments and analysis on mechanical instabilities for the relevant case of a bacterial biofilm grown during flow enable us to predict and control the biofilm morphology., eLife, 11, ISSN:2050-084X

Streptomycin (STR) and dihydrostreptomycin (DSTR) are the typically encountered aminoglycoside (AMG) residues in honey. For AMG analysis, studies in literature involve impractical and expensive applications such as ion-pairing chromatography, immunoassays, pre and post column derivatizations, or SPE approaches. Pre -treatments of these methods are toilsome and costly. Herein, one-pot, aqueous in-situ derivatization method was presented as a superior protocol. Time and cost-efficient UHPLC-MS/MS method has been developed, and practical sample preparation was introduced. Satisfactory results were reported in method verification studies. The mean recovery values were 102.6% for STR and 101.3% for DSTR. Average values between 1.5% and 9.9% RSDs were found at intra and inter-day precisions. CC alpha (5.7 and 5.8 mu g/kg) and CC beta (6.2 and 6.4 mu g/kg) values were calculated for STR and DSTR respectively. AMG residues were found in 29 out of 110 analyzed samples using validated method. Described novelty enabled comprehensive analysis in an inexpensive and straightfor-ward manner.

The Pacific island nation of Vanuatu is vulnerable to emerging infectious diseases, including epidemics and pandemics; chronic food and water insecurity; and natural hazards, including cyclones, earthquakes, tsunamis, landslides and flooding. In March 2020, the World Health Organization characterized the outbreak of novel coronavirus disease 2019 (COVID-19) as a global pandemic. By the end of April 2020, Vanuatu had reported no confirmed cases of COVID-19. Data from several sources are collected in Vanuatu’s COVID-19 surveillance system to provide an overview of the situation, including data from case investigations and management, syndromic surveillance for influenza-like illness, hospital surveillance and laboratory surveillance. Review of data collected from January to the end of April 2020 suggests that there was no sustained increase in influenza-like illness in the community and no confirmed cases were identified. Lessons learnt from the early implementation of surveillance activities, the changing landscape of laboratory testing and pharmaceutical interventions, as well as the global experience, particularly in other Pacific island countries, will inform the refinement of COVID-19 surveillance activities in Vanuatu.

International borders to Vanuatu closed on 23 March 2020 due to the global COVID-19 pandemic. In May–July 2020, the Government of Vanuatu focused on the safe and timely return of citizens and residents while ensuring Vanuatu remained COVID-19 free. Under Phase 1 of repatriation, between 27 May and 23 June 2020, 1522 people arrived in the capital, Port Vila, and were placed in compulsory government-mandated 14-day quarantine in 15 hotels. Pre-arrival health operations included collection of repatriate information, quarantine facility assessments, training for personnel supporting the process, and tabletop and functional exercises with live scenario simulations. During quarantine, health monitoring, mental health assessments and psychosocial support were provided. All repatriates completed 14 days of quarantine. One person developed symptoms consistent with COVID-19 during quarantine but tested negative. Overall health operations were considered a success despite logistical and resource challenges. Lessons learnt were documented during a health sector after-action review held on 22 July 2020. Key recommendations for improvement were to obtain timely receipt of repatriate information before travel, limit the number of repatriates received and avoid the mixing of “travel cohorts”, ensure sufficient human resources are available to support operations while maintaining other essential services, establish a command and control structure for health operations, develop training packages and deliver them to all personnel supporting operations, and coordinate better with other sectors to ensure health aspects are considered. These recommendations were applied to further improve health operations for subsequent repatriation and quarantine, with Phase 2 commencing on 1 August 2020.

Problem From December 2016 to February 2017, two cases of invasive meningococcal disease and one case of meningococcal conjunctivitis, all serogroup W, occurred in Aboriginal children in the Ceduna region of South Australia. The clustering of cases in time and place met the threshold for a community outbreak. Context The Ceduna region is a remote part of South Australia, with more than 25% of the population identifying as Aboriginal or Torres Strait Islander. Action As part of the outbreak response, a community-wide meningococcal vaccination programme against serogroups A, C, W and Y was implemented in a collaboration among different agencies of the South Australia Department for Health and Well-being, Aboriginal health and community services providers, and other local service providers and government agencies. The programme comprised an outbreak vaccination schedule, targeting all people aged 3 2 months residing in the cases’ places of residence or in towns with close links. Outcome Between March and June 2017, 3383 persons were vaccinated, achieving an estimated coverage of 71–85% of the target population, with 31% (n = 1034) of those vaccinated identifying as Aboriginal or Torres Strait Islander. No local cases of serogroup W occurred during the vaccination programme, but two further cases were notified by the end of 2018. Discussion The participation of a large number of local and non-health-sector stakeholders in programme planning and implementation, a clear response management structure and high community acceptability were identified as key factors that contributed to the programme achieving high vaccination coverage. The need to develop standard operating procedures for community-based outbreak response interventions to ease logistical challenges was considered an important lesson learnt.

Introduction: The 4-aminoquinolines, chloroquine, and hydroxychloroquine have been used for over 70 years for malaria and rheumatological conditions, respectively. Their broad-spectrum antiviral activity, excellent safety profile, tolerability, low cost, and ready availability made them prime repurposing therapeutic candidates at the beginning of the COVID-19 pandemic. Areas covered: Here, the authors discuss the history of hydroxychloroquine and chloroquine, the in vitro data which led to their widespread repurposing and adoption in COVID-19 and their complex pharmacokinetics. The evidence for the use of these drugs is assessed through in vivo animal experiments and the wealth of conflicting data and interpretations published during COVID-19, including the more informative results from randomized controlled trials (RCTs). The safety aspects of these drugs, in particular cardiotoxicity, are then reviewed. Expert opinion: The evidence from clinical trials in COVID-19 supports the well-established safety record of the 4-aminoquinolines at currently recommended dosage. In hospitalized patients with severe COVID-19 RCTs show clearly that the 4-aminoquinolines are not beneficial. The only treatments with proven benefit at this stage of infection are immunomodulators (dexamethasone, IL-6 receptor antagonists). No antiviral drugs have proven life-saving in late-stage COVID-19.

Adverse reactions to food or food ingredients are more often perceived than objectively verifiable. However, reliable laboratory tests are often lacking. As a result, people with perceived adverse reactions to food often follow extensive elimination diets for years and unnecessarily restrict their diet, as in the case of the frequently suspected histamine intolerance. In this condition, laboratory parameters such as the determination of diamine oxidase in serum have been shown to be inconclusive. The lack of symptom reproducibility calls into question the clinical picture of adverse reactions to ingested histamine. In order to approach persons with perceived histamine intolerance and to support them in moving from blanket restrictions, which are often unnecessarily strict, to effective personalized therapeutic strategies, the present guideline of the Working Group on Food Allergy of the German Society of Allergology and Clinical Immunology (DGAKI) in cooperation with the Medical Association of German Allergists (AeDA), the Pediatric Allergology and Environmental Medicine (GPA) as well as the Swiss Society of Allergology and Immunology (SGAI) and the Austrian Society of Allergology and Immunology (ÖGAI) recommends a practicable diagnostic and therapeutic approach.

“Intensified TB research and innovation” is one of the three pillars of the End TB Strategy. To assess achievements and gaps in tuberculosis (TB) research productivity in countries and areas of the Western Pacific Region quantitatively, a bibliometric analysis was carried out by examining trends in the numbers of publications on TB indexed in PubMed between 2000 and 2019 and by comparing them with trends in publications on other selected major infectious diseases for the same period. The number of publications on TB in the Region increased by 3.2 times during the period, from 534 in 2000–2004 to 1714 in 2015–2019, as compared with 2.9 times each for HIV, hepatitis and malaria. The number increased by 46% in 2005–2009, 79% in 2010–2014 and 23% in 2015–2019, as compared with each previous 5-year period. The average annual growth rate between 2000 and 2018 was 8.8%. China accounted for 34.8% of the total number of publications on TB in the Region. Increases in TB research were observed in most countries and areas in the Region, particularly in those with a high TB burden. The number of publications on TB remained low, however, in the Lao People’s Democratic Republic, Mongolia and Pacific island countries. Countries are encouraged to implement the set of actions proposed in the Global Strategy for TB Research and Innovation to accelerate progress towards ending TB.

Introduction: At 11:20 on 26 May 2018, a physician from Lianyungang No. 1 People’s Hospital, China, reported that six family members were being treated in the hospital with symptoms from an unknown cause. Methods: A case series for a food poisoning investigation and an environmental survey were conducted. The patients and their relatives were interviewed in person with a questionnaire contained on a digital tablet, and an investigation of the patients’ home was conducted in the presence of police officers. Probable case and confirmed case were defined to serve as a basis for identifying additional cases. Confirmed cases were defined as those probable cases in which blood, stool or vomitus specimens tested positive for paliperidone palmitate and/or its metabolites. A descriptive analysis was performed. Follow-up by telephone was conducted four months later. Results: There were six probable cases. The median age was 35 years (range: 5–76 years). The attack rate was 100% (n = 6/6) of persons who consumed a family dinner, and the hospitalization rate was also 100% (n = 6/6). The median period between exposure and symptom onset was two hours. The main symptoms included vomiting, nausea, drowsiness, dizziness and severe abdominal pain for adults, and vomiting and severe lethargy for children. An 8-year-old girl further showed changes in the ST segment of her electrocardiogram, and a 5-year-old boy showed QT prolongation. The poisoning substance was suspected to be paliperidone palmitate based on the patients’ symptoms and epidemiological findings. Discussion: We investigated the household food poisoning outbreak through epidemiological analysis and an environmental investigation and determined that it was caused by paliperidone palmitate. The source of the paliperidone palmitate was found to be aluminium containers, taken home by the eldest son who worked at a pharmaceutical company. The containers were sent to a drug disposal centre, and the pharmaceutical company was required to enhance the regulation on the pharmaceutical waste materials to prevent drug poisoning events. By the end of September 2018, the six patients recovered and were released from the hospital, and they did not show any clinical sequelae in four follow-up visits.

Since 2015, the End TB Strategy and the Regional Framework for Action on Implementation of the End TB Strategy in the Western Pacific 2016–2020 have guided national tuberculosis (TB) responses in countries and areas of the Region. This paper provides an overview of the TB epidemiological situation in the Western Pacific Region and of progress towards the 2020 milestones of the Strategy. A descriptive analysis was conducted of TB surveillance and programme data reported to WHO and estimates of the TB burden generated by WHO for the period 2000–2018. An estimated 1.8 million people developed TB and 90 000 people died from it in the Region in 2018. Since 2015, the estimated TB incidence rate and the estimated number of TB deaths in the Region decreased by 3% and 10%, with annual reduction rates of 1.0% and 3.4%, respectively. With current efforts, the Region is unlikely to achieve the 2020 milestones and other targets of the Strategy. Major challenges include: (1) wide variation in the geographical distribution and rate of TB incidence among countries; (2) a substantial proportion (23%) of TB cases that remain unreached, undiagnosed or unreported; (3) insufficient coverage of drug susceptibility testing (51%) for bacteriologically confirmed cases and limited use of WHO-recommended rapid diagnostics (11 countries reported

SummaryHow environmental cues influence peroxisome proliferation, particularly through other organelles, remains largely unknown. Yeast peroxisomes metabolize all fatty acids (FA), and methylotrophic yeasts also metabolize methanol. NADH and acetyl-CoA, the products of these pathways enter mitochondria for ATP production, and for anabolic reactions. During the metabolism of FA and/or methanol, the mitochondrial oxidative phosphorylation (OXPHOS) pathway accepts NADH for ATP production and maintains cellular redox balance. Remarkably, peroxisome proliferation in Pichia pastoris was abolished in NADH shuttling and OXPHOS mutants affecting complex I or III, or by the mitochondrial uncoupler, 2,4-dinitrophenol (DNP), indicating ATP depletion causes the phenotype. We show that mitochondrial OXPHOS deficiency inhibits the expression of several peroxisomal proteins implicated in FA and methanol metabolism, as well as in peroxisome division and proliferation. These genes are regulated by the Snf1 complex (SNF1), a pathway generally activated by high AMP and low ATP. Consistent with this mechanism, in OXPHOS mutants, Snf1 is activated by phosphorylation, but Gal83, its interacting subunit, fails to translocate to the nucleus. Phenotypic defects in peroxisome proliferation observed in the OXPHOS mutants, and phenocopied by the Δgal83 mutant, were rescued by deletion of three transcriptional repressor genes (MIG1, MIG2 and NRG1) controlled by SNF1 signaling. We uncovered here the mechanism by which peroxisomal and mitochondrial metabolites influence redox and energy metabolism, while also influencing peroxisome biogenesis and proliferation, thereby exemplifying interorganellar communication and interplay involving peroxisomes, mitochondria, cytosol and the nucleus. We discuss the physiological relevance of this work in view of human OXPHOS deficiencies.

Photosystem I (PSI) is a multi-subunit pigment-protein complex that functions in light-harvesting and photochemical charge-separation reactions, followed by reduction of NADP to NADPH required for CO2 fixation in photosynthetic organisms. PSI from different photosynthetic organisms has a variety of chlorophylls (Chls), some of which are at lower-energy levels than its reaction center P700, a special pair of Chls, and are called low-energy Chls. However, the sites of low-energy Chls are still under debate. Here, we solved a 2.04-Å resolution structure of a PSI trimer by cryo-electron microscopy from a primordial cyanobacterium Gloeobacter violaceus PCC 7421, which has no low-energy Chls. The structure shows the absence of some subunits commonly found in other cyanobacteria, confirming the primordial nature of this cyanobacterium. Comparison with the known structures of PSI from other cyanobacteria and eukaryotic organisms reveals that one dimeric and one trimeric Chls are lacking in the Gloeobacter PSI. The dimeric and trimeric Chls are named Low1 and Low2, respectively. Low2 is missing in some cyanobacterial and eukaryotic PSIs, whereas Low1 is absent only in Gloeobacter. These findings provide insights into not only the identity of low-energy Chls in PSI, but also the evolutionary changes of low-energy Chls in oxyphototrophs.

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX expression rescued this phenotype. These studies show that NAD+ regeneration represents a major role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.

Background:Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified Shigella spp. as the first and second most predominant agent of dysentery and moderate diarrhoea, respectively. Antimicrobial therapy is often necessary for Shigella infections; however, we are reaching a crisis point with efficacious antimicrobials. The rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem.Methods:Aiming to identify alternative antimicrobial chemicals with activity against antimicrobial resistant Shigella, we initiated a collaborative academia-industry drug discovery project, applying high-throughput phenotypic screening across broad chemical diversity and followed a lead compound through in vitro and in vivo characterisation.Results:We identified several known antimicrobial compound classes with antibacterial activity against Shigella. These compounds included the oral carbapenem Tebipenem, which was found to be highly potent against broadly susceptible Shigella and contemporary MDR variants for which we perform detailed pre-clinical testing. Additional in vitro screening demonstrated that Tebipenem had activity against a wide range of other non-Shigella enteric bacteria. Cognisant of the risk for the development of resistance against monotherapy, we identified synergistic behaviour of two different drug combinations incorporating Tebipenem. We found the orally bioavailable prodrug (Tebipenem pivoxil) had ideal pharmacokinetic properties for treating enteric pathogens and was effective in clearing the gut of infecting organisms when administered to Shigella-infected mice and gnotobiotic piglets.Conclusions:Our data highlight the emerging antimicrobial resistance crisis and shows that Tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) should be accelerated into human trials and could be repurposed as an effective treatment for severe diarrhoea caused by MDR Shigella and other enteric pathogens in LMICs.Funding:Tres Cantos Open Lab Foundation (projects TC239 and TC246), the Bill and Melinda Gates Foundation (grant OPP1172483) and Wellcome (215515/Z/19/Z).

Key Points Question How does the prevalence of hypertension in pregnant women change when using the 2017 American College of Cardiology/American Heart Association definition, which is lower than the American College of Obstetricians and Gynecologists threshold, and is there an association with maternal or fetal outcomes? Findings In this cohort study that included 137 389 pregnancies, the prevalence of hypertension increased from 10.3% to 28.1% and resulted in a net reclassification index of 20.8% for the identification of future preeclampsia and 3.8% for the identification of fetal/neonatal adverse events. Meaning These findings suggest that applying the lower diagnostic thresholds to pregnant women may better identify women at risk of adverse events., This cohort study estimates the prevalence of hypertension among pregnant women using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definition of hypertension instead of the American College of Obstetricians and Gynecologists threshold and assesses identification of adverse maternal or fetal outcomes associated with use of the ACC/AHA guidelines., Importance Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and mortality. The impact of applying recent guideline definitions for nonpregnant adults to pregnant women is unclear. Objective To determine whether reclassification of hypertensive status using the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline definition better identifies women at risk for preeclampsia or eclampsia and adverse fetal/neonatal events compared with the current American College of Obstetricians and Gynecologists (ACOG) definition of hypertension. Design, Setting, and Participants This cohort study used electronic medical record data of women who delivered singleton infants between 2009 and 2014 at a large US regional health system. Data analysis was performed from July 2020 to September 2020. Exposure Application of ACC/AHA and ACOG guidelines for the definition of chronic and gestational hypertension. Main Outcomes and Measures The primary maternal end point was the development of preeclampsia or eclampsia, and the primary fetal/neonatal end point was a composite of preterm birth, small for gestational age, and neonatal intensive care unit admission within 28 days of delivery. Net reclassification indices were calculated to examine how well the lower ACC/AHA diagnostic threshold reclassifies outcomes of pregnancy compared with the current ACOG definition of hypertension. Results Applying the ACC/AHA criteria to 137 389 pregnancies of women (mean [SD] age at time of delivery, 30.1 [5.8] years) resulted in a 14.3% prevalence of chronic hypertension (19 621 pregnancies) and a 13.8% prevalence of gestational hypertension (18 998 pregnancies). A 17.8% absolute increase was found in the overall prevalence of hypertension from 10.3% to 28.1%. The 2.1% of women who were reclassified with chronic rather than gestational hypertension had the highest risk of developing preeclampsia compared with women without hypertension by either criterion (adjusted risk ratio, 13.58; 95% CI, 12.49-14.77). Overall, the use of the ACC/AHA criteria to diagnose hypertension resulted in a 20.8% improvement in the appropriate identification of future preeclampsia, but only a 3.8% improvement of appropriate fetal/neonatal risk classification. Conclusions and Relevance Using the lower diagnostic threshold for hypertension recommended in the 2017 ACC/AHA guideline increased the prevalence of chronic and gestational hypertension, markedly improved the appropriate identification of women who would go on to develop preeclampsia, and was associated with the identification of adverse fetal/neonatal risk.

Problem: Over 290 million people worldwide suffer from chronic hepatitis B (CHB), with the highest prevalence in the Pacific islands. Mortality attributable to this disease exceeds that from HIV, tuberculosis and malaria combined in this region. Context: CHB is a major health problem in the Pacific island nation of Kiribati. Medical care is complicated by vast expanses of ocean separating population centres in its constituent islands. Birth-dose hepatitis B immunization rates need improvement. High rates of obesity, metabolic syndrome, and co-infection with hepatitis B and hepatitis D in Kiribati make treatment less effective. Staff allocation, training and retention are difficult. Limited infrastructure creates challenges in training, communications, laboratory testing and record-keeping. Action: We have established a CHB treatment programme in Kiribati based on World Health Organization (WHO) guidelines and local needs. It includes direct patient care; laboratory, radiology and pharmacy support; public education; training; and data management. Thousands of individuals have been screened, and 845 hepatitis B-positive patients have had blood sent to Australia for molecular testing. Patient education pamphlets, medical training programmes and treatment protocols have been developed. Seventy-nine patients have started treatment. Regular onsite visits by technical experts are scheduled throughout the year. Lessons learnt and discussion: This is the first national CHB treatment programme established in the Pacific islands region. Unique challenges exist in Kiribati, as they do in each nation affected by CHB. Close engagement with local partners, knowledge of the barriers involved, flexibility, advocacy, and support from WHO and volunteer technical experts are key attributes of a successful treatment programme.

In this paper we consider the hypo-q-operator norm and hypo-q-numerical radius on a Cartesian product of algebras of bounded linear operators on Banach spaces. A representation of these norms in terms of semi-inner products, the equivalence with the q-norms on a Cartesian product and some reverse inequalities obtained via the scalar reverses of Cauchy-Buniakowski-Schwarz inequality are also given.

Lung cancer is known as lung carcinoma. It is a disease which is malignant tumor leading to the uncontrolled cell growth in the lung tissue. Lung cancer is caused generally by smoking and the use of tobacco products. It is classified into two broad Small-cell lung Carcinomas and non-Small cell lung carcinomas. Lung cancer treatments include surgery, radiation therapy, chemotherapy, and targeted therapy. Lung Cancer disease is one of the most prominent cause of death in all over world. Early detection of this disease can assist medical care unit as well as physicians to provide counter measures to the patients. The objective of this paper is to approach an automated tool that takes influential causes of lung cancer as input and detect patients with higher probabilities of being affected by this disease. A neural network classifier accompanied by k-fold cross-validation technique is proposed in this paper as a predictive tool. Later, this proposed method is compared with another baseline classifier Gradient Boosting Classifier in order to justify the prediction performance. Experimental results conclude that analyzing interfering causes of lung cancer can effectively accomplish disease classification model with an accuracy of 95%.

The article is devoted to the analysis of the image of a person of a different nationality, who is created in his works by the modern Russian science fiction writer Oleg Divov. Based on the analysis of the author’s three novels, “The Best Solar Crew,” “Technical Support” and “Elephants’ Homeland,” his original attitude to the problem of the national and ethnic affiliation of a person is revealed. The aim of the study was to analyze the image of a person of a different nationality in the books of O.I. Divov and to represent a person of a different nationality in the context of the image of the “Other”. The tasks were set to identify the author’s treatment of the image of a person of a different nationality, to detect interpretations of this image in various works. The scientific novelty of the study was provided both by the novelty of the text material introduced into the scientific circulation, and by the approach to the problem of the image of the “Other” in modern literature from the point of view of the optionality of observing the principles of tolerance and political correctness, more precisely, new ways of observing these principles. In the reviewed works of the writer, heroes of different nationalities appear, and the national differences between them are not hidden, but, on the contrary, stand out in relief, are brought to the fore. Representatives of each of the nationalities (Russians, Jews, Germans, Americans, French, Chukchi, and others) are portrayed as people with undeniable merits, and at the same time – ironically, with humor. The writer does not demonstrate any stable national preferences: in the novel “The Best Solar Crew”, Russians are glorified first of all, and in the novel “The Land of Elephants” – the Chukchi. Despite ridicule, reflecting the stereotypical perception of a particular nation, the description of none of them becomes nationalistic. The author creates an original concept of perception of heroes of a different nationality, opposing the popular in modern culture of tolerance, showing the importance of national differences and the uselessness of silencing them.

Resilience embodies the personal qualities that enable one to thrive in the face of adversity. A previous Italian study showed that injured workers had a lower level of resilience than non-injured workers. The aim of this paper is to examine the relationship between occupational injuries and psychological resilience. The subjects were 197 drivers from two Finnish waste transport companies. As a part of larger questionnaire, they fulfilled the Connor-Davidson Resilience Scale, which consisted of 25 items. Drivers reported their occupational injuries during the last three years. The drivers involved in occupational injuries had higher score (average 69.3) on Connor-Davidson Resilience Scale than drivers avoided injuries (67.7). According to Student’s t-test the difference between groups was highly significant (t = 40.44, df = 196, p

Salt taste sensation is multifaceted: NaCl at low or high concentrations is preferably or aversively perceived through distinct pathways. Cl−is thought to participate in taste sensation through an unknown mechanism. Here we describe Cl−ion binding and the response of taste receptor type 1 (T1r), a receptor family composing sweet/umami receptors. The T1r2a/T1r3 heterodimer from the medaka fish, currently the sole T1r amenable to structural analyses, exhibited a specific Cl−binding in the vicinity of the amino-acid-binding site in the ligand-binding domain (LBD) of T1r3, which is likely conserved across species, including human T1r3. The Cl−binding induced a conformational change in T1r2a/T1r3LBD at sub-to low-mM concentrations similar to canonical taste substances. Furthermore, oral Cl−application to mice increased impulse frequencies of taste nerves connected to T1r-expressing taste cells and promoted their behavioral preferences attenuated by a T1r-specific blocker or T1r3 knock-out. These results suggest that the Cl−evokes taste sensations by binding to T1r, thereby serving as another preferred salt taste pathway at a low concentration.

Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus Campylobacter, there are species with divergent ecologies, from rarely isolated single-host specialists to multihost generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterizing these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analyzing recipient and donor population ancestry among genomes from 30 Campylobacter species, we show that cohabitation in the same host can lead to a six-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.

The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved "snowflake" yeast and the green alga $Volvox~carteri$. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing., Comment: 28 pages, 7 figures

Funder: Isaac Newton Trust; FundRef: http://dx.doi.org/10.13039/501100004815, Funder: Alborada Trust; FundRef: http://dx.doi.org/10.13039/100008288, Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440, Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735, Funder: Global Health Innovative Technology Fund; FundRef: http://dx.doi.org/10.13039/501100013996, Funder: Rosetrees Trust; FundRef: http://dx.doi.org/10.13039/501100000833, Funder: Royal Society; FundRef: http://dx.doi.org/10.13039/501100000288, HAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in Plasmodium have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of Plasmodium berghei HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of Plasmodium berghei in vitro and transmission of malaria in mosquitoes. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the Plasmodium D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission.

Schuster et al. make the important observation that small numbers of trypanosomes can infect tsetse flies, and further argue that this can occur whether the infecting parasites are developmentally 'slender' or 'stumpy'(Schuster et al., 2021). We welcome their careful experiments but disagree that they require a rethink of the trypanosome life-cycle. Instead, the study reveals that stumpy forms are more likely to successfully infect flies, the key limit on parasite transmission, and we predict this advantage would be greatly amplified in tsetse infections in the field. Further, we argue that stumpy forms are defined by a suite of molecular adaptations for life-cycle progression, with morphology being a secondary feature. Finally, their dominance in chronic infections means most natural tsetse infections would involve stumpy forms, even in small numbers. Our interpretation does not require re-evaluation of the obligatory life cycle of the parasite, where stumpy forms are selected to sustain transmission.

Schuster et al. make the important observation that small numbers of trypanosomes can infect tsetse flies, and further argue that this can occur whether the infecting parasites are developmentally ‘slender’ or ‘stumpy’(Schuster et al., 2021). We welcome their careful experiments but disagree that they require a rethink of the trypanosome life-cycle. Instead, the study reveals that stumpy forms are more likely to successfully infect flies, the key limit on parasite transmission, and we predict this advantage would be greatly amplified in tsetse infections in the field. Further, we argue that stumpy forms are defined by a suite of molecular adaptations for life-cycle progression, with morphology being a secondary feature. Finally, their dominance in chronic infections means most natural tsetse infections would involve stumpy forms, even in small numbers. Our interpretation does not require re-evaluation of the obligatory life cycle of the parasite, where stumpy forms are selected to sustain transmission.

Energy conservation in microorganisms is classically categorized into respiration and fermentation; however, recent work shows some species can use mixed or alternative bioenergetic strategies. We explored the use of extracellular electron transfer for energy conservation in diverse lactic acid bacteria (LAB), microorganisms that mainly rely on fermentative metabolism and are important in food fermentations. The LABBacteria produce the energy they need to live through two processes, respiration and fermentation. While respiration is often more energetically efficient, many bacteria rely on fermentation as their sole means of energy production. Respiration normally depends on the presence of small soluble molecules, such as oxygen, that can diffuse inside the cell, but some bacteria can use metals or other insoluble compounds found outside the cell to perform ‘extracellular electron transfer’. Lactic acid bacteria are a large group of bacteria that have several industrial uses and live in many natural environments. These bacteria survive using fermentation, but they also carry a group of genes needed for extracellular electron transfer. It is unclear whether they use these genes for respiration or if they have a different purpose. Tejedor-Sanz, Stevens et al. used a lactic acid bacterium called