The F plasmid conjutome: the repertoire of E. coli proteins translocated through an F-encoded type IV secretion system.

Bacterial conjugation systems pose a major threat to human health through their widespread dissemination of mobile genetic elements (MGEs) carrying cargoes of antibiotic resistance genes. Using the Cre Recombinase Assay for Translocation (CRAfT), we recently reported that the IncFV pED208 conjugation system also translocates at least 16 plasmid-encoded proteins to recipient bacteria. Here, we deployed a high-throughput CRAfT screen to identify the repertoire of chromosomally encoded protein substrates of the pED208 system. We identified 32 substrates encoded by the Escherichia coli W3110 genome with functions associated with (i) DNA/nucleotide metabolism, (ii) stress tolerance/physiology, (iii) transcriptional regulation, or (iv) toxin inhibition. The respective gene deletions did not impact pED208 transfer proficiencies, nor did Group 1 (DNA/nucleotide metabolism) mutations detectably alter the SOS response elicited in new transconjugants upon acquisition of pED208. However, MC4100(pED208) donor cells intrinsically exhibit significantly higher SOS activation than plasmid-free MC4100 cells, and this plasmid carriage-induced stress response is further elevated in donor cells deleted of several Group 1 genes. Among 10 characterized substrates, we gained evidence of C-terminal or internal translocation signals that could function independently or synergistically for optimal protein transfer. Remarkably, nearly all tested proteins were also translocated through the IncN pKM101 and IncP RP4 conjugation systems. This repertoire of E. coli protein substrates, here termed the F plasmid "conjutome," is thus characterized by functions of potential benefit to new transconjugants, diverse TSs, and the capacity for promiscuous transfer through heterologous conjugation systems. IMPORTANCE: Conjugation systems comprise a major subfamily of the type IV secretion systems (T4SSs) and are the progenitors of a second large T4SS subfamily dedicated to translocation of protein effectors. This study examined the capacity of conjugation machines to function as protein translocators. Using a high-throughput reporter screen, we determined that 32 chromosomally encoded proteins are delivered through an F plasmid conjugation system. The translocated proteins potentially enhance the establishment of the co-transferred F plasmid or mitigate mating-induced stresses. Translocation signals located C-terminally or internally conferred substrate recognition by the F system and, remarkably, many substrates also were translocated through heterologous conjugation systems. Our findings highlight the plasticity of conjugation systems in their capacities to co-translocate DNA and many protein substrates.

Chimeric systems composed of swapped Tra subunits between distantly-related F plasmids reveal striking plasticity among type IV secretion machines.

Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity. Here, we explored the structural bases underlying the functional versatility of T4SSs through systematic deletion and subunit swapping between two conjugation systems encoded by the distantly-related IncF plasmids, pED208 and F. We identified several regions of intrinsic flexibility among the encoded T4SSs, as evidenced by partial or complete functionality of chimeric machines. Swapping of VirD4-like TraD type IV coupling proteins (T4CPs) yielded functional chimeras, indicative of relaxed specificity at the substrate-TraD and TraD-T4SS interfaces. Through mutational analyses, we further delineated domains of the TraD T4CPs contributing to recruitment of cognate vs heterologous DNA substrates. Remarkably, swaps of components comprising the outer membrane core complexes, a few F-specific subunits, or the TraA pilins supported DNA transfer in the absence of detectable pilus production. Among sequenced enterobacterial species in the NCBI database, we identified many strains that harbor two or more F-like plasmids and many F plasmids lacking one or more T4SS components required for self-transfer. We confirmed that host cells carrying co-resident, non-selftransmissible variants of pED208 and F elaborate chimeric T4SSs, as evidenced by transmission of both plasmids. We propose that T4SS plasticity enables the facile assembly of functional chimeras, and this intrinsic flexibility at the structural level can account for functional diversification of this superfamily over evolutionary time and, on a more immediate time-scale, to proliferation of transfer-defective MGEs in nature.

Undulating Seal Whiskers Evolved Optimal Wavelength-to-Diameter Ratio for Efficient Reduction in Vortex-Induced Vibrations.

Seals are well-known for their remarkable hydrodynamic trail-following capabilities made possible by undulating flow-sensing whiskers that enable the seals to detect fish swimming as far as 180 m away. In this work, the form-function relationship in the undulating whiskers of two different phocid seal species, viz. harbor and gray seals, is studied. The geometry and material properties of excised harbor and grey seal whiskers are systematically characterized using blue light 3D scanning, optical and scanning electron microscopy, and nanoindentation. The effect of the undulating geometry on the whiskers' vibration in uniform water flow is studied using both experimental (piezoelectric MEMS and 3D-printed piezoresistive sensors developed in-house) and numerical (finite element method) techniques. The results indicate that the dimensionless ratio of undulation wavelength to mean whisker diameter (λ/Dm ) in phocid seals may have evolved to be in the optimal range of 4.4-4.6, enabling an order-of-magnitude reduction in vortex-induced vibrations (compared to a similarly-shaped circular cylinder) and, consequently, an enhanced flow sensing capability with minimal self-induced noise. The results highlight the importance of the dimensionless λ/Dm ratio in the biomimetic design of seal whisker-inspired vibration-resistant structures, such as marine risers and wake detection sensors for submarines.

Chimeric systems composed of swapped Tra subunits between distantly-related F plasmids reveal striking plasticity among type IV secretion machines.

Bacterial type IV secretion systems (T4SSs) are a versatile family of macromolecular translocators, collectively able to recruit diverse DNA and protein substrates and deliver them to a wide range of cell types. Presently, there is little understanding of how T4SSs recognize substrate repertoires and form productive contacts with specific target cells. Although T4SSs are composed of a number of conserved subunits and adopt certain conserved structural features, they also display considerable compositional and structural diversity. Here, we explored the structural bases underlying the functional versatility of T4SSs through systematic deletion and subunit swapping between two conjugation systems encoded by the distantly-related IncF plasmids, pED208 and F. We identified several regions of intrinsic flexibility among the encoded T4SSs, as evidenced by partial or complete functionality of chimeric machines. Swapping of VirD4-like TraD type IV coupling proteins (T4CPs) yielded functional chimeras, indicative of relaxed specificity at the substrate - TraD and TraD - T4SS interfaces. Through mutational analyses, we further delineated domains of the TraD T4CPs contributing to recruitment of cognate vs heterologous DNA substrates. Remarkably, swaps of components comprising the outer membrane core complexes, a few F-specific subunits, or the TraA pilins supported DNA transfer in the absence of detectable pilus production. Among sequenced enterobacterial species in the NCBI database, we identified many strains that harbor two or more F-like plasmids and many F plasmids lacking one or more T4SS components required for self-transfer. We confirmed that host cells carrying co-resident, non-selftransmissible variants of pED208 and F elaborate chimeric T4SSs, as evidenced by transmission of both plasmids. We propose that T4SS plasticity enables the facile assembly of functional chimeras, and this intrinsic flexibility at the structural level can account for functional diversification of this superfamily over evolutionary time and, on a more immediate time-scale, to proliferation of transfer-defective MGEs in nature.

Denosumab Use in Chronic Kidney Disease Associated Osteoporosis: A Narrative Review.

Chronic kidney disease (CKD) and hemodialysis (HD) patients have a high incidence of bone disease and increased fracture risk, making effective management of their bone health a clinical challenge. Denosumab, a human monoclonal antibody, has been investigated as a therapeutic option in this patient population. In this review, we summarize the current evidence on the efficacy and safety of denosumab in CKD and HD patients. A comprehensive search of the relevant literature was conducted, including randomized controlled trials, observational studies, and meta-analyses. The findings suggest that denosumab reduces the risk of fractures and improves bone mineral density in all stages of CKD. The results of this review support the use of denosumab as a promising option for managing bone disease in CKD and HD patients.

Induction of labour at 39 weeks and adverse outcomes in low-risk pregnancies according to ethnicity, socioeconomic deprivation, and parity: A national cohort study in England.

BACKGROUND: Ethnic and socioeconomic inequalities in obstetric outcomes are well established. However, the role of induction of labour (IOL) to reduce these inequalities is controversial, in part due to insufficient evidence. This national cohort study aimed to identify adverse perinatal outcomes associated with IOL with birth at 39 weeks of gestation ("IOL group") compared to expectant management ("expectant management group") according to maternal characteristics in women with low-risk pregnancies. METHODS AND FINDINGS: All English National Health Service (NHS) hospital births between January 2018 and March 2021 were examined. Using the Hospital Episode Statistics (HES) dataset, maternal and neonatal data (demographic, diagnoses, procedures, labour, and birth details) were linked, with neonatal mortality data from the Office for National Statistics (ONS). Women with a low-risk pregnancy were identified by excluding pregnancies with preexisting comorbidities, previous cesarean section, breech presentation, placenta previa, gestational diabetes, or a baby with congenital abnormalities. Women with premature rupture of membranes, placental abruption, hypertensive disorders of pregnancy, amniotic fluid abnormalities, or antepartum stillbirth were excluded only from the IOL group. Adverse perinatal outcome was defined as stillbirth, neonatal death, or neonatal morbidity, the latter identified using the English composite neonatal outcome indicator (E-NAOI). Binomial regression models estimated risk differences (with 95% confidence intervals (CIs)) between the IOL group and the expectant management group, adjusting for ethnicity, socioeconomic background, maternal age, parity, year of birth, and birthweight centile. Interaction tests examined risk differences according to ethnicity, socioeconomic background, and parity. Of the 1 567 004 women with singleton pregnancies, 501 072 women with low-risk pregnancies and with sufficient data quality were included in the analysis. Approximately 3.3% of births in the IOL group (1 555/47 352) and 3.6% in the expectant management group (16 525/453 720) had an adverse perinatal outcome. After adjustment, a lower risk of adverse perinatal outcomes was found in the IOL group (risk difference -0.28%; 95% CI -0.43%, -0.12%; p = 0.001). This risk difference varied according to socioeconomic background from 0.38% (-0.08%, 0.83%) in the least deprived to -0.48% (-0.76%, -0.20%) in the most deprived national quintile (p-value for interaction = 0.01) and by parity with risk difference of -0.54% (-0.80%, -0.27%) in nulliparous women and -0.15% (-0.35%, 0.04%) in multiparous women (p-value for interaction = 0.02). There was no statistically significant evidence that risk differences varied according to ethnicity (p = 0.19). Key limitations included absence of additional confounding factors such as smoking, BMI, and the indication for induction in the HES datasets, which may mean some higher risk pregnancies were included. CONCLUSIONS: IOL with birth at 39 weeks was associated with a small reduction in the risk of adverse perinatal outcomes, with 360 inductions in low-risk pregnancies needed to avoid 1 adverse outcome. The risk reduction was mainly present in women from more socioeconomically deprived areas and in nulliparous women. There was no significant risk difference found by ethnicity. Increased uptake of IOL at 39 weeks, especially in women from more socioeconomically deprived areas, may help reduce inequalities in adverse perinatal outcomes.

Electronic Structure Engineered Heteroatom Doped All Transition Metal Sulfide Carbon Confined Heterostructure for Extrinsic Pseudocapacitor.

Ultra-high energy density battery-type materials are promising candidates for supercapacitors (SCs); however, slow ion kinetics and significant volume expansion remain major barriers to their practical applications. To address these issues, hierarchical lattice distorted α-/γ-MnS@Cox Sy core-shell heterostructure constrained in the sulphur (S), nitrogen (N) co-doped carbon (C) metal-organic frameworks (MOFs) derived nanosheets (α-/γ-MnS@Cox Sy @N, SC) have been developed. The coordination bonding among Cox Sy , and α-/γ-MnS nanoparticles at the interfaces and the π-π stacking interactions developed across α-/γ-MnS@Cox Sy and N, SC restrict volume expansion during cycling. Furthermore, the porous lattice distorted heteroatom-enriched nanosheets contain a sufficient number of active sites to allow for efficient electron transportation. Density functional theory (DFT) confirms the significant change in electronic states caused by heteroatom doping and the formation of core-shell structures, which provide more accessible species with excellent interlayer and interparticle conductivity, resulting in increased electrical conductivity. . The α-/γ-MnS@Cox Sy @N, SC electrode exhibits an excellent specific capacity of 277 mA hg-1 and cycling stability over 23 600 cycles. A quasi-solid-state flexible extrinsic pseudocapacitor (QFEPs) assembled using layer-by-layer deposited multi-walled carbon nanotube/Ti3 C2 TX nanocomposite negative electrode. QFEPs deliver specific energy of 64.8 Wh kg-1 (1.62 mWh cm-3 ) at a power of 933 W kg-1 and 92% capacitance retention over 5000 cycles.

Rare Case of Tongue Ischemia Following Cardiopulmonary Bypass.

Tongue ischemia is a devastatingly rare disease complication that is typically attributed to cranial arteritis, vasculitis, or prolonged oral intubation that manifests in a patient as a phenotypically black or discolored tongue. There have been less than 10 cases reported in the literature, however, documenting tongue ischemia secondary to shock states requiring high-dose vasopressor support. In these cases, the ischemia or necrosis has typically been limited to the tip of the tongue or has been associated with unilateral disease as bilateral tongue involvement is unlikely given the collateral blood supply of the tongue. To date, the use of imaging modalities to confirm lingual artery disease as the etiology for the presentation of tongue ischemia has been limited. We present a unique case of bilateral tongue ischemia following the use of cardiopulmonary bypass which was confirmed with radiographic evidence demonstrating bilateral lingual artery disease. The nature of case is presented, previous reports of similar cases are reviewed, and potential etiologies of this rare manifestation are discussed.

Initiator AUGs Are Discriminated from Elongator AUGs Predominantly through mRNA Accessibility in C. crescentus.

The initiation of translation in bacteria is thought to occur upon base pairing between the Shine-Dalgarno (SD) site in the mRNA and the anti-SD site in the rRNA. However, in many bacterial species, such as Caulobacter crescentus, a minority of mRNAs have SD sites. To examine the functional importance of SD sites in C. crescentus, we analyzed the transcriptome and found that more SD sites exist in the coding sequence than in the preceding start codons. To examine the function of SD sites in initiation, we designed a series of mutants with altered ribosome accessibility and SD content in translation initiation regions (TIRs) and in elongator AUG regions (EARs). A lack of mRNA structure content is required for initiation in TIRs, and, when introduced into EARs, can stimulate initiation, thereby suggesting that low mRNA structure content is a major feature that is required for initiation. SD sites appear to stimulate initiation in TIRs, which generally lack structure content, but SD sites only stimulate initiation in EARs if RNA secondary structures are destabilized. Taken together, these results suggest that the difference in secondary structure between TIRs and EARs directs ribosomes to start codons where SD base pairing can tune the efficiency of initiation, but SDs in EARs do not stimulate initiation, as they are blocked by stable secondary structures. This highlights the importance of studying translation initiation mechanisms in diverse bacterial species. IMPORTANCE Start codon selection is an essential process that is thought to occur via the base pairing of the rRNA to the SD site in the mRNA. This model is based on studies in E. coli, yet whole-genome sequencing revealed that SD sites are absent at start codons in many species. By examining the transcriptome of C. crescentus, we found more SD-AUG pairs in the CDS of mRNAs than preceding start codons, yet these internal sites do not initiate. Instead, start codon regions have lower mRNA secondary structure content than do internal SD-AUG regions. Therefore, we find that start codon selection is not controlled by the presence of SD sites, which tune initiation efficiency, but by lower mRNA structure content surrounding the start codon.

Prevalence of Cardiovascular Risk Factors and 10-Years Risk for Coronary Heart Disease in the United Arab Emirates.

BACKGROUND: In the United Arab Emirates (UAE), cardiovascular diseases (CVDs) are the leading cause of mortality, and the incidence of premature coronary heart diseases (CHDs) is about 10-15 years earlier than that in people of western countries. AIM: The current cross-sectional study aims to describe the prevalence of CVD risk factors and estimate the 10-years risk for CHDs in the population of Abu Dhabi, UAE. OBJECTIVE: The main objective was to report the 10-years risk for CHD in a sample of the UAE population. METHODS: We have analyzed the dataset from the Abu Dhabi Screening Program for Cardiovascular Risk Markers (AD-SALAMA), a population-based cross-sectional survey conducted between 2009 and 2015 (a sample of 1002, 20 to 79 years old without CVDs or diabetes). RESULTS: 18.0% of our sample have had hypertension (HTN), 26.3% were current smokers, 33% have had total cholesterol ≥200 mg/dL, 55.0% have had non-high-density lipoprotein (non-HDL) levels ≥130 mg/dL, 33.1% have had low-density lipoprotein cholesterol (LDL-C) levels ≥130 mg/dL, calculated by ß-quantification as 112.3 ± 47.1 mg/dL. 66.8% were overweight or obese, and 46.2% had a sedentary lifestyle. Nearly 85% of our sample has had one or more major cardiovascular risk factors. The estimated 10-year risk of cardiovascular disease according to different risk assessment tools was as follows: 7.1% according to the national cholesterol education program Framingham risk score (FRAM-ATP), 2.9% according to Pooled Cohort Risk Assessment Equation (PCRAE) , 1.4% according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and 1.1% according to Reynolds Risk Score. Despite the fact that our sample population have had exhibited major risk factors, the above-mentioned international scoring systems underestimate the 10-year risk of cardiovascular diseases, given the high prevalence at younger ages. CONCLUSION: The proportion of modifiable risk factors has been found to be high in the UAE population, and the majority of them have had one or more risk factors with a higher 10-years risk for CHDs.

Reconfiguring the Electronic Structure of Heteroatom Doped Carbon Supported Bimetallic Oxide@Metal Sulfide Core-Shell Heterostructure via In Situ Nb Incorporation toward Extrinsic Pseudocapacitor.

High-energy-density battery-type materials have sparked considerable interest as supercapacitors electrode; however, their sluggish charge kinetics limits utilization of redox-active sites, resulting in poor electrochemical performance. Here, the unique core-shell architecture of metal organic framework derived N-S codoped carbon@Cox Sy micropetals decorated with Nb-incorporated cobalt molybdate nanosheets (Nb-CMO4 @Cx Sy NC) is demonstrated. Coordination bonding across interfaces and π-π stacking interactions between CMO4 @Cx Sy and N and, S-C can prevent volume expansion during cycling. Density functional theory analysis reveals that the excellent interlayer and the interparticle conductivity imparted by Nb doping in heteroatoms synergistically alter the electronic states and offer more accessible species, leading to increased electrical conductivity with lower band gaps. Consequently, the optimized electrode has a high specific capacity of 276.3 mAh g-1 at 1 A g-1 and retains 98.7% of its capacity after 10 000 charge-discharge cycles. A flexible quasi-solid-state SC with a layer-by-layer deposited reduced graphene oxide /Ti3 C2 TX anode achieves a specific energy of 75.5 Wh kg-1 (volumetric energy of 1.58 mWh cm-3 ) at a specific power of 1.875 kWh kg-1 with 96.2% capacity retention over 10 000 charge-discharge cycles.

Wavy Whiskers in Wakes: Explaining the Trail-Tracking Capabilities of Whisker Arrays on Seal Muzzles.

Seals can detect prey up to 180 m away using only their flow-sensing whiskers. The unique undulating morphology of Phocid seal whiskers reduces vortex-induced vibrations (VIVs), rendering seals highly sensitive to biologically relevant flow stimuli. In this work, digital models of harbor and grey seal whiskers are extracted using 3D scanning and a mathematical framework that accurately recreates their undulating geometry is proposed. Through fluid-structure interaction studies and experimental investigations involving a whisker array mounted on 3D-printed microelectromechanical systems sensors, the vibration characteristics of the whisker array and the interaction between neighboring whiskers in steady flows and fish-wake-like vortices are explained for the first time. Results reveal that the downstream vortices intensity and resulting VIVs are consistently lower for grey than harbor seal whiskers and a smooth cylinder, suggesting that the grey seal whisker geometry can be an ideal template for the biomimetic design of VIV-resistant underwater structures. In addition, neighboring whiskers in an array influence one another by resulting in greater flow vorticity fluctuation and distribution area, thus causing increased vibrations than an isolated whisker, which indicates the possibility of a signal-strengthening effect in whisker arrays.

Introduction to the Special Issue-Cardiothoracic Surgical Critical Care: A Future of Distinction.

Critical care after cardiothoracic surgery is an inseparable component of any successful surgical program addressing intrathoracic pathologies, including heart failure treatment with mechanical circulatory support, and respiratory failure requiring extracorporeal membrane oxygenation (ECMO) therapy [...].

A Brief History of Cardiothoracic Surgical Critical Care Medicine in the United States.

Cardiothoracic surgical intensive care has developed in response to advances in cardiothoracic surgery. The invention of the cardiopulmonary bypass machine facilitated a motionless and bloodless surgical field and made operations of increasing complexity feasible. By the mid-1950s, the first successful procedures utilizing cardiopulmonary bypass took place. This was soon followed by the establishment of postoperative recovery units, the precursors to current cardiothoracic surgical intensive care units. These developments fostered the emergence of a new medical specialty: the discipline of critical care medicine. Together, surgeons and intensivists transformed the landscape of acute, in-hospital care. It is important to celebrate these achievements by remembering the individuals responsible for their conception. This article describes the early days of cardiothoracic surgery and cardiothoracic intensive care medicine.

Developing Cardiothoracic Surgical Critical Care Intensivists: A Case for Distinct Training.

Cardiothoracic surgical critical care medicine is practiced by a diverse group of physicians including surgeons, anesthesiologists, pulmonologists, and cardiologists. With a wide array of specialties involved, the training of cardiothoracic surgical intensivists lacks standardization, creating significant variation in practice. Additionally, it results in siloed physicians who are less likely to collaborate and advocate for the cardiothoracic surgical critical care subspeciality. Moreover, the current model creates credentialing dilemmas, as experienced by some cardiothoracic surgeons. Through the lens of critical care anesthesiologists, this article addresses the shortcomings of the contemporary cardiothoracic surgical intensivist training standards. First, we describe the present state of practice, summarize past initiatives concerning specific training, outline why standardized education is needed, provide goals of such training standardization, and offer a list of desirable competencies that a trainee should develop to become a successful cardiothoracic surgical intensivist.

IncFV plasmid pED208: Sequence analysis and evidence for translocation of maintenance/leading region proteins through diverse type IV secretion systems.

Two phylogenetically distantly-related IncF plasmids, F and pED208, serve as important models for mechanistic and structural studies of F-like type IV secretion systems (T4SSFs) and F pili. Here, we present the pED208 sequence and compare it to F and pUMNF18, the closest match to pED208 in the NCBI database. As expected, gene content of the three cargo regions varies extensively, although the maintenance/leading regions (MLRs) and transfer (Tra) regions also carry novel genes or motifs with predicted modulatory effects on plasmid stability, dissemination and host range. By use of a Cre recombinase assay for translocation (CRAfT), we recently reported that pED208-carrying donors translocate several products of the MLR (ParA, ParB1, ParB2, SSB, PsiB, PsiA) intercellularly through the T4SSF. Here, we extend these findings by reporting that pED208-carrying donors translocate 10 additional MLR proteins during conjugation. In contrast, two F plasmid-encoded toxin components of toxin-antitoxin (TA) modules, CcdB and SrnB, were not translocated at detectable levels through the T4SSF. Remarkably, most or all of the pED208-encoded MLR proteins and CcdB and SrnB were translocated through heterologous T4SSs encoded by IncN and IncP plasmids pKM101 and RP4, respectively. Together, our sequence analyses underscore the genomic diversity of the F plasmid superfamily, and our experimental data demonstrate the promiscuous nature of conjugation machines for protein translocation. Our findings raise intriguing questions about the nature of T4SS translocation signals and of the biological and evolutionary consequences of conjugative protein transfer.

Distress symptoms during the COVID-19 lockdown: A study with the general population of the United Arab Emirates.

Background: Since the declaration of the COVID-19 pandemic, the United Arab Emirates (UAE) government has taken a series of preventive measures to control the spread of the Coronavirus. Dealing with the unforeseen challenges caused by the pandemic has had a profound impact on people all around the world. Pharmacists played an important public health role during the COVID-19 pandemic, and they were the first point of contact with the public and the first source of information, providing accurate and reliable management and preventive measures. The aim of this study was to analyse the distress symptoms and the associated factors among a sample of the UAE population. Materials and Methods: This was an observational cross-sectional study conducted over the period of September to October 2020. A bilingual online self-administered questionnaire was distributed among individuals aged 15 years and above. Data was analyzed using Statistical Package for Social Sciences (SPSS). Results: Most of the students in the sample found online learning less effective than in-class learning. Among these, 49.9% and 62.8 % reported that they had normal sleep and eating habits, respectively. In all the sample, most of the participants (96%) were adherent to preventive measures. Higher levels of distress during the COVID-19 lockdown were found among females, individuals younger than 35 years old, those who neglected personal hygiene and who had worse quality of family gatherings and relationships. Conclusion: This study identified factors associated with distress symptoms experienced by people during the lockdown and perceived attitudes regarding online learning, preventive measures and changes in people's behaviours and family environment. Knowledge about how lockdown has affected the lives of the populations can be used to design public health interventions aimed at promoting the health and well-being of the communities.

Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study.

The phase 3 HESTIA3 study assessed the efficacy and safety of the reversible P2Y12 inhibitor ticagrelor vs placebo in preventing vaso-occlusive crises in pediatric patients with sickle cell disease (SCD). Patients aged 2 to 17 years were randomly assigned 1:1 to receive weight-based doses of ticagrelor or matching placebo. The primary end point was the rate of vaso-occlusive crises, a composite of painful crises and/or acute chest syndrome (ACS). Key secondary end points included number and duration of painful crises, number of ACS events, and number of vaso-occlusive crises requiring hospitalization or emergency department visits. Exploratory end points included the effect of ticagrelor on platelet activation. In total, 193 patients (ticagrelor, n = 101; placebo, n = 92) underwent randomization at 53 sites across 16 countries. The study was terminated 4 months before planned completion for lack of efficacy. Median ticagrelor exposure duration was 296.5 days. The primary end point was not met: estimated yearly incidence of vaso-occlusive crises was 2.74 in the ticagrelor group and 2.60 in the placebo group (rate ratio, 1.06; 95% confidence interval, 0.75-1.50; P = .7597). There was no evidence of efficacy for ticagrelor vs placebo across secondary end points. Median platelet inhibition with ticagrelor at 6 months was 34.9% predose and 55.7% at 2 hours' postdose. Nine patients (9%) in the ticagrelor group and eight patients (9%) in the placebo group had at least one bleeding event. In conclusion, no reduction of vaso-occlusive crises was seen with ticagrelor vs placebo in these pediatric patients with SCD. This trial was registered at www.clinicaltrials.gov as #NCT03615924.

Impacts of COVID-19 Pandemic on Geopolitics, Health, Economics, Education and Sociocultural Events.

The number of active cases of COVID-19 and deaths is markedly escalating. The pandemic had affected almost every aspect of our lives including geopolitics, health, economics, education, and sociocultural events. However, besides the negative impacts of the pandemic, there are some positive impacts as well, such as improving our awareness of the daily hygienic practices, emphasizing digital inequality, and increasing global collaboration in combating the crisis by intensifying scientific research to establish a promising vaccine. Other positive impacts are the activation and use of online education, also raising awareness about close family relationships and much more. This review addresses the impacts of the COVID-19 pandemic on various important aspects of life.

Geophysical imaging of buried human remains in simulated mass and single graves: Experiment design and results from pre-burial to six months after burial.

In this study, we present an experiment design and assess the capability of multiple geophysical techniques to image buried human remains in mass and individual graves using human cadavers willingly donated for scientific research. The study is part of a novel, interdisciplinary mass grave experiment established in May 2021 which consists of a mass grave with 6 human remains, 3 individual graves and 2 empty control graves dug to the same size as the mass grave and individual graves. Prior to establishing the graves, we conducted background measurements of electrical resistivity tomography (ERT), electromagnetics (EM), and ground penetrating radar (GPR) while soil profiles were analyzed in situ after excavating the graves. All graves were also instrumented with soil sensors for monitoring temporal changes in soil moisture, temperature, and electrical conductivity in situ. Measurements of ERT, EM and GPR were repeated 3, 37, 71 and 185 days after burial with further repeated measurements planned for another twelve months. ERT results show an initial increase in resistivity in all graves including the control graves at 3 days after burial and a continuous decrease thereafter in the mass and individual graves with the strongest decrease in the mass grave. Conductivity distribution from the EM shows a similar trend to the ERT with an initial decrease in the first 3 days after burial. Distortion in linear reflectors, presence of small hyperbolas and isolated strong amplitude reflectors in the GPR profiles across the graves is associated with known locations of the graves. These initial results validate the capability of geoelectrical methods in detecting anomalies associated with disturbed ground and human decay while GPR though show some success is limited by the geology of the site.