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Induction regarding Parthenogenesis by Irradiated Pollen in Cucurbita Types.
Ultrasound examination compared to Calculated Tomography Assessment of Major Bronchi Aeration in Invasively Aired ICU Sufferers.
11±670.73pg/ml) than both newly diagnosed (4842.44±489.40pg/ml) and HAART (4660.31±519.83pg/ml) groups, while significant decrease in haematocrit was observed between the newly diagnosed group (0.336±0.07l/l) as against both treated (0.378±0.04l/l) and control (0.362±0.02l/l) groups. D-dimer correlated negatively with serum p53 protein level among the newly diagnosed subjects and with Hb Conc. among subjects undergoing treatment. The study concludes that women of reproductive age living with HIV infection showed higher D-dimer and lower tumour suppression protein levels as well as anaemia and reduced immune response. The newly diagnosed subjects were more affected.Kolaviron is a mixture of bi-flavonoids from seed Garcinia kola seed, and has been previously shown to exhibit Nrf2 antioxidant-mediated inhibition of neuroinflammation in LPS-activated BV2 microglia. In this study, we investigated neuroprotective effects of kolaviron in LPS-induced memory impairment in rats. Wistar rats (225-250) g was used for this study. Memory impairment was induced with the systematic administration of 250 µg/mg lipopolysaccharide (LPS). The effect of kolaviron on the cognition and learning processes were assessed using the behavioral responses in the Morris water maze model. Effects of LPS injections on the physiological activities were assessed by biochemical assays before and after treatment. Peripheral administration of LPS showed reduction in the cognitive and locomotor process. It also led to reductions in the core body temperature, superoxide dismutase (SOD), and catalase levels, with an increase in Membrane lipid-peroxidation (MDA), intracellular glutathione (GSH) and nitric oxide (NO2). These pro-inflammatory mediators produced in response to LPS are hypothesized to affect cognition, and kolaviron was able to ameliorate the effect by significantly improving the cognitive and learning processes, revealed in the reduction of escape latency and path-length during the probe trial and increase in time spent within the quadrant during retrieval using Morris water maze. see more Similarly, LPS at 250 µg/kg induced a hypothermic effect in the treated animals. Kolaviron significantly was able to ameliorate the level of SOD and CAT by causing a significant increase while it caused a significant reduction in the level of NO2, GSH, and MDA. Kolaviron has considerable anti-inflammatory potentials, reducing lipopolysaccharide activation of macrophages. The memory-enhancing activity of kolaviron was comparable to Sulindac sulfide (a non-steroidal anti-inflammatory drug).Hyperlipidemia is emerging as an important cause of adverse health outcomes including cardiovascular complications, obesity, metabolic disorders, and infertility. A total of twenty-five (25) male albino Wistar rats were divided into five groups (n=5) Normal control, Hyperlipidemic control group which was administered (intra-peritoneal) with 0.2ml/10g body weight of egg yolk and then terminated after twenty-four (24) hours, Hyperlipidemic non-treated group which were administered with 0.2ml/10g body weight of egg yolk and were left throughout the treatment period. Hyperlipidemic low-dose treated group (administered 0.2ml/10g body weight of egg yolk, 800mg/kg body weight of methanolic extract of Citrullus lanatus seed-MECLS), and Hyperlipidemic high-dose treated group (administered 0.2ml/10g body weight of egg yolk, and 1600mg/kg body weight of MECLS). No significant change was observed in testosterone levels and sperm count across all groups. However, a statistically significant increase (P less then 0.05) in luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels was observed in Hyperlipidemic non-treated and Hyperlipidemic low-dose treated group when compared to Normal Control Group. They also showed marked testicular damage and significantly decreased (P less then 0.05) sperm cell motility and significantly increased sperm cell abnormalities. Hyperlipidemic low and high dose groups exhibited moderate and complete regeneration of testicular histo-architecture respectively. Furthermore, high dose treated group showed a significant decrease in sperm count, motility, LH and FSH levels. This study suggests that MECLS dose dependently ameliorates testicular damage induced by hyperlipidemia but may affect sperm cell characteristics.This study aimed at assessing the knowledge base and perception of telemedicine among veterinary students in Ghana. It involved a cross sectional survey and online structured questionnaires were administered to 114 veterinary students to access their knowledge of telemedicine and the perceived utilisation, benefits, complexity and disadvantages of telemedicine. Descriptive statistics analysis was performed on the data collected using SPSS version 20 and Pearson Chi-square test was used to determine the significant association between categorical variables which were grouped. Statistical significance was tested at 5% significance level. The students exhibited good knowledge and perception of telemedicine with a mean response of 4.947 ± 1.374 and 3.473±1.115; represented by 86.8% and 78.9% of the students respectively. 92.1% had heard of the term 'telemedicine' from the internet and social media platforms. The level of study of veterinary students had a significant effect (p less then 0.05) on their knowledge of telemedicine; knowledge increases with an increase in the year of study. Veterinary students showed good knowledge level and perception of telemedicine. However, exposure to the use of telemedicine system is low. Issues of patients' information privacy being threatened by the usage of telemedicine were indicated. Development, incorporation of telemedicine in the curriculum in formative years of veterinary students training is critical to ensure effective and efficient training of students in telemedicine in the COVID era.In this study, the effects of maternal exposure to Bonny Light Crude Oil (BLCO) on reproductive functions of the offspring was investigated in Wistar rats. Ten pregnant rats were divided into two groups (n=5). Group 1 served as the control, it was administered 0.75ml/Kg bwt/day normal saline and Group 2 was administered 0.75ml/Kg bwt/day BLCO. Serum hormonal profile, sperm indices, estrous cycle length and pubertal timing were assessed as measures of reproductive function. Tissue Malondialdehyde, Catalase and SOD activities were assessed as indices of oxidative stress. Results obtained showed that BLCO significantly (p less then 0.05) reduced birth weight, anogenital distance (AGD) at birth, sperm count, motility and normal morphology, serum testosterone, testicular and epididymal SOD and catalase activities in the male offsprings. However, days of preputial separation, relative weight of testis and epididymis, testicular and epididymal MDA were significantly (p less then 0.05) raised by gestational exposure to BLCO. In the female offspring, birth weight, AGD at birth, relative weight of ovaries and uterus, SOD, catalase activities, serum LH were significantly reduced by BLCO exposure during gestation. Moreover, uterine and testicular MDA, serum estradiol and FSH were significantly increased by BLCO treatment during gestation. In conclusion, maternal exposure to BLCO during gestation may alter reproductive indices in the offspring and increased occurrence of oxidative stress in reproductive structures in male and female offspring of Wistar rats.This study evaluates the therapeutic potentials of selected antihypertensive drugs [valsartan, amlodipine, lisinopril and their fixed-dose combinations (amlodipine + lisinopril) and (valsartan + lisinopril)] in ameliorating trastuzumab (TZM)‑induced cardiac dysfunctions in experimental rats. After an ethical clearance for the study was obtained, in-bred young adult female Wistar rats were randomly allotted into 10 groups of 6 rats per group. Group I rats were treated with 10 ml/kg/day sterile water p.o. and 1 ml/kg/day sterile water i.p.; Group II, III and IV rats were orally treated with 5 mg/kg/day VAL and 1 ml/kg/day sterile water i.p., 0.25 mg/kg/day ADP and 1 ml/kg/day sterile water i.p., 0.035 mg/kg/day LSP and 1 ml/kg/day sterile water i.p., respectively. Group V rats were orally pretreated with 10 ml/kg/day of sterile water before i.p. 2.25 mg/kg/day of TZM. Groups VI-VIII rats were equally pretreated with 5 mg/kg/day VAL, 0.25 mg/kg/day ADP, and 0.035 mg/kg/day LSP before i.p. 2.25 mg/kg/day TZM trea associated with histopathological lesions of coronary arterial wall cartilaginous metaplasia. Overall, this study revealed the promising therapeutic potentials of VAL, ADP, LSP and their fixed-dose combinations as repurposed drugs for the prevention of TZM-mediated cardiac dysfunctions.Pandemics have claimed an estimated 414 million lives from 165 AD to present, with COVID-19 pandemic killing close to 2 million people. The best counter for pandemics has been the use of vaccines, but before it is widely available, the best strategy is to avoid being infected. COVID-19 pandemic was met by behaviours and attitudes ranging from unbelief to fear of dying and stigmatisation of those who have contracted the virus or recovered from the disease. This study aimed to investigate the knowledge, attitudes, practices (KAP), fear and stigma of the populace towards COVID-19 from state to state. This research was a cross-sectional study carried out from April to October 2020. Data was obtained through a structured questionnaire distributed to 650 individuals. link=see more Respondents who participated were 591 (males n= 335 and females n= 256) and aged 18-60 years (mean age 30.25 ± 10.45 years, range 18-60) drawn from five states in the north-central region of Nigeria. The results show that 98.3% of participants believe that COVID-19 disease exists. Still, not everyone wears face masks, avoid crowded places, practice social distancing or follow the WHO-hand-washing technique as measures to curb the spread of the disease. Only 60.5% of the participants believe that lockdown is an effective measure to reduce transmission risk. 55.6% will stigmatise those who just recovered from the disease, 75.3% are afraid to visit high-risk areas as part of the protective measures, but only about 12% believe that every infected person will die. More males (28.3%) than females (17.6%) believe that taking herbs can cure the disease (P less then 0.01). All government and nongovernmental organizations must develop more awareness programs to win the battle against COVID-19 disease as the second wave is emerging.Pregnancy is thus characterized by an anti-inflammatory milieu in the second trimester despite a pro-inflammatory response in the first and third trimesters. Nonetheless a disproportionate inflammatory response is risky in pregnancy. This retrospective study evaluated the mid-gestational expression of inflammatory and anti-inflammatory cytokines in HIV infected pregnant women at their first antenatal visit. Archived serum samples were collected from seventy (n=70) black pregnant women, attending a primary health care centre in KwaZulu-Natal, South Africa. The demographic and clinical profiles were procured from patient medical records and cytokine levels were measured in all samples. A statistical significance (p less then 0.05) was noted for IP-10 between the HIV positive and HIV negative groups for the inflammatory, anti-inflammatory cytokines and chemokines when stratified by HIV status. Likewise, IL-7 was statistically different when the HIV population was stratified based on ART usuage. Significant correlations were noted between IL-7 and birthweight (r=0.35, p less then 0.05); IFN-δ and maternal age (r=-0.27, p less then 0.05); TNF-α and gestational age (r=0.26, p less then 0.05); VEGF and systolic blood pressure (r=0.40, p less then 0.05); IL-4 and gestational age (r=-0.30, p less then 0.05). A positive correlation was noted for inflammatory IL-1b with anti-inflammatory IL-5, IL-5 and FGF basic; inflammatory IL-2 with anti-inflammatory IL-5, IL-10 as well as FGF basic. A negative correlation between the inflammatory IL-12 with anti-inflammatory IL-1ra and Il-4 as well as that between IL-17A with IL-10 was noted. This study reveals midgestational variation in serum inflammatory and anti-inflammatory immunologic profile of pregnant women, irrespective of the use of antiretroviral therapy. This disparity in the susceptible HIV infected women will affect progression of pregnancy and encourage fetal morbidity and mortality.Parkinson's disease (PD) and dementia with Lewy bodies have several commonalities including neurochemical, morphological and clinical features as well as widespread of cortical and limbic α-synuclein and amyloid-β pathologies. Thus, we evaluated the action of hesperidin on α-synuclein and amyloid-β-induced neurodegeneration in Drosophila melanogaster. The disease causing human Aβ peptide or α- synuclein was expressed respectively, in Elav-GAL4 (pan-neuronally) and dopaminergic neurons (ddc-GAL4) using the UAS-GAL4 system. Flies were either grown on food media supplemented with or without hesperidin (HSD) (1, 5, or 10mM). Behavioral assays were carried to investigate the effect of treatment on fecundity, larval motility, climbing ability and lifespan. Aβ>Elav or α-syn>DDC caused significant decrease in fecundity, larva contraction, motility, survival rate, and climbing activities in flies indicative of neurodegeneration. However, supplementation of flies' media with hesperidin (1mM, 5mM and 10mM) showed a dose-dependent increase in the number of line crosses in the egg laying, larva motility, climbing activity in comparison with flies grown on food media only. Conversely, supplementation of fly feed with HSD caused no significant change in lifespan. Findings from this experiment showed that hesperidin could be a potential neuroprotective agent in the amelioration of PD and AD pathogenesis.Thyroid hormones have been shown to promote the generation of reactive oxygen species (ROS), consumption of antioxidants, and induction of oxidative stress, which triggers the release of heat shock proteins (HSPs) and VEGF-dependent angiogenesis. The present study investigated the effect of altered thyroid states, hypothyroidism and hyperthyroidism on hepatic and renal functions, oxidative stress biomarkers, and hepatorenal expressions of HSP70, HSP90, and VEGF. Male Wistar rats were randomized into vehicle-treated control, carbimazole-induced hypothyroidism, or levothyroxine-induced hyperthyroidism. Altered thyroid states caused impaired hepatic and renal functions accompanied by elevated malondialdehyde and reduced glutathione content and superoxide dismutase and catalase activities in the hepatic and renal tissues. These derangements were associated with down-regulation of hepatic and renal HSP70 and HSP90 and upregulation of hepatic and renal VEGF expression. Findings of histopathological examinations of the hepatic and renal tissues align with the biochemical derangements observed. This study reveals that dysthyroidism impairs hepatorenal function via induction of oxidative stress and modulation of HSP70/HSP90/VEGF signaling.Tooth-wear signatures obtained from maxillary carnassial fourth premolar teeth of raccoons in three ecologic regions in Nigeria testified to segregations in diet of the species with more abrasive diet in specimens from coastal south-western areas compared to more vegetal diet content of those from middle belt and northern areas. Endoloph assessments showed sexually dimorphic mesowear signals between and within locations suggestive that males are more exposed to dental wears compared to females; Male and female specimens from rainforest zone had 40.2% and 34.2% respectively, Sudan Savanna zone had 46.8% and 40.6% for females and males while 67.6% and 44.3% for Sahel zone specimens in similar order. We investigated dietary resource use for sustained survivability within limits of interspecific spatial overlaps using seasonal rainfall indices between two years. There was 86% per high dental occlusal surface relief in the specimens from the savannas while 32% per low relief was observed in South-Western badgers teeth samples. This study observed a change in habitat use as a predisposing factor to sub-regional dental wear differences among age groups as well as sexes of species from three geographic climatic areas. The richness of the eco-habitat/life expectancy found in the rain forest can be ascribed to diet availability which is reduced in the savanna areas. The study suggests minimal change in habitat use as a predisposing factor in sub-regional species dental relief differences observed among age groups and sexes of the species from three geographic climatic areas and also represents quality of the eco-habitats.Mercury is an environmental neurotoxicant that triggers structural and physiological alterations in different brain parts. The hippocampus is associated with learning and memory, and injury to this brain part may lead to behavioural and cognitive changes. Phoenix dactylifera (date palm) has been demonstrated to possess a variety of medical benefits. This study comparatively assessed the neuroprotective property of aqueous and ethanol fruit pulp extracts of P. dactylifera in a rat model of mercury-triggered hippocampal changes using microscopic examinations. Twenty-eight Wistar rats were divided into seven groups (I-VII, n=4). Group I (control) was administered distilled water (2ml/kg); group II was administered mercuric chloride, HgCl2 (5mg/kg); group III was administered vitamin C (100mg/kg) as reference drug +HgCl2; groups IV and V were administered aqueous extract (250mg/kg and 500mg/kg, respectively) +HgCl2, while groups VI and VII were administered ethanol extract (250mg/kg and 500mg/kg, respectively) +HgCl2. Extracts' neuroprotective property were evaluated using histological and histometric assessments of CA1 and CA3 hippocampal sub-regions. Results revealed cytoarchitectural changes including karyopyknosis, basophilic necrosis and remarkably decreased histometric features of hippocampal pyramidal neurons in HgCl2-treated group relative to control. Administration of the extracts remarkably ameliorated mercury-induced degenerative changes by preservation of cytoarchitectural features comparable to reference drug. link2 Comparatively, neuroprotective efficacies of the extracts are relatively similar, especially at doses of 500mg/kg and could be attributed to antioxidant activities of constituent phytochemicals. Results suggest that aqueous and ethanol fruit pulp extracts of P. dactylifera may prove efficacious in ameliorating mercury-triggered microscopic alterations in the hippocampus of Wistar rats.COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) enters the host cells through attachment to the Angiotensin Converting Enzyme-2 receptors (ACE-2) on the host cells. ACE-2 is known to affect renal functions, vasoconstriction and fluid homeostasis. Thus, the impact of SARS-CoV-2 infection on renal functional parameters is worth investigating. Plasma obtained from whole blood samples collected from newly diagnosed COVID-19 patients were analysed for albumin, urea, creatinine, Na, K, Cl and HCO3 using auto analysers. All newly diagnosed patients were immediately admitted for managed at the Infectious Disease Center, Olodo in Ibadan the capital of Oyo State, South Western Nigeria. The results obtained were evaluated to determine the frequency of derangements in the renal parameters of patients with the COVID-19 disease. It was observed that 57.1%, 37.8%, 32.7%, 28.1%, 18.7%, 17.8% and 3.4% of newly diagnosed COVID-19 patients had values of Cl, creatinine, albumin, Na, K, HCO3 and urea respectively outside the reference ranges. While 43.3%, 4.7%, 2.5%, 2.5%, 2.0%, 1.7% and 1.0% of COVID-19 patients had values of Cl, creatinine, Na, K, albumin, Urea and HCO3 respectively above the reference ranges. Of all admitted patients, 33.1%, 30.7%, 25.6%, 16.8%, 16.3%, 13.8% and 1.7% had creatinine, albumin, Na, HCO3, K, Cl and urea values respectively below reference ranges. The changes in renal function parameters of newly diagnosed COVID-19 patients portend that renal failure is imminent in poorly managed COVID-19 patients and this has immunopathology implications during SAR-COV-2 infection.
El objetivo de este estudio fue caracterizar la clasificación hemodinámica de la hipertensión pulmonar en una serie de pacientes llevados a cateterismo cardíaco derecho.

Se realizó un estudio retrospectivo y se revisaron los registros de los cateterismos cardíacos derechos practicados en personas mayores de 18 años entre enero de 2017 y diciembre del 2018. see more Se excluyó a aquéllos con datos incompletos o no concluyentes y se definieron los perfiles hemodinámicos de acuerdo con el resultado de la presión en cuña y la resistencia vascular pulmonar.

Se incluyó a 92 sujetos de los cuales se descartó hipertensión pulmonar en 4. El 26.1% se clasificó como precapilar, 31.8% como poscapilar y 42% como combinada. No hubo diferencias entre los tres grupos en edad y sexo; las presiones pulmonares fueron más elevadas en el grupo de hipertensión pulmonar precapilar. Se encontró presión en cuña elevada en el 73.8% de los pacientes y el cateterismo derecho reclasificó al 35% de los pacientes en un grupo hemodinámico difeprecapillary, 31.8% postcapillary and 42% as combined pulmonary hypertesion. There were no differences between the 3 groups in age or sex, pulmonary pressures were higher in the precapillary pulmonary hypertension group, right catheterization reclassified 35% of the patients in a hemodynamic group in a different from that expected. Precapillary PH was suspected in most of these cases, but the hemodynamic profiles found in cardiac catheterization corresponded to post-capillary or combined pulmonay hypertension.

Right heart catheterization is necessary for the hemodynamic classification of pulmonary hypertension, which is important not only for diagnosis but also for evaluating the etiology of the disease.
Right heart catheterization is necessary for the hemodynamic classification of pulmonary hypertension, which is important not only for diagnosis but also for evaluating the etiology of the disease.A young female patient with normal ejection fraction. History of premature ventricular complex (PVC) radiofrequency ablation located in left ventricular outflow tract. Two years later frequent PVC is observed in a different location (> 47000 in 24 h Holter). Anti-arrhythmic drugs were used unsuccessfully. PVCs were located in left ventricular summit. Radiofrequency ablation through coronary sinus and anterior interventricular vein was performed. During follow up no recurrence was observed.A young female patient with normal ejection fraction. History of premature ventricular complex (PVC) radiofrequency ablation located in left ventricular outflow tract. Two years later frequent PVC is observed in a different location (> 47000 in 24 h Holter). Anti-arrhythmic drugs were used unsuccessfully. PVCs were located in left ventricular summit. Radiofrequency ablation through coronary sinus and anterior interventricular vein was performed. During follow up no recurrence was observed.As one of the neglected tropical diseases, leishmaniasis is defined as a parasitic communicable disease that is most prevalent in tropical and subtropical regions, affecting especially populations living in poverty. It has a profound negative impact on developing economies. It represents a group of heterogeneous syndromes with a wide spectrum of severity ranging from self-resolving cutaneous injuries to disseminated visceral compromise. Visceral leishmaniasis represents its most severe form, can affect almost all organs, and can have fatal consequences, especially in immunosuppressed patients. Cardiac involvement seems to be rare but has not been deeply studied. Consequently, there are no clear recommendations for the screening of cardiac manifestations in these patients. However, cardiovascular complications could be potentially lethal. In addition, there are valuable reports on the potential cardiotoxicity caused by drugs used in the treatment of this condition, so knowledge of its side effects could have important implications. This article is a part of the "Neglected Tropical Diseases and other Infectious Diseases affecting the Heart" project (the NET-Heart Project); its purpose is to review all the information available regarding cardiac implications of this disease and its treatment and to add knowledge to this field of study, focusing on the barriers for diagnosis and treatment, and how to adopt strategies to overcome them.
Gender-based differences among cardiology professionals have been reported in North America and Europe. However, the perspective of Latin American cardiologists remains unexplored.

The objectives of the study were to analyze the gender gap perspective among cardiologists from Latin America.

A cross-sectional study using an online survey directed to Latin American cardiologists from five different cardiology societies. The survey included questions on demographic data, professional development in the field of cardiology, and perceived barriers in clinical practice.

A total of 240 professionals were surveyed, of which 41.7% were women (100) and 58.3% were men (140). The majority of women tend to work in the subfields of clinical cardiology and cardiovascular imaging. Women were underrepresented as heads of departments, earn less, and report less work satisfaction than men. The barriers that female cardiologists face at their workplace include labor discrimination, sexual harassment, family-related concerns, and lack of career development.

The survey points toward the prevalence of a gender gap among cardiologists in Latin America, which is primarily driven by labor discrimination, sexual harassment, family-related concerns, and lack of career development among female cardiologists. Actions aimed at addressing this issue should be considered by different parties.
The survey points toward the prevalence of a gender gap among cardiologists in Latin America, which is primarily driven by labor discrimination, sexual harassment, family-related concerns, and lack of career development among female cardiologists. Actions aimed at addressing this issue should be considered by different parties.Intellectual disability and autism spectrum disorder (ASD) are common, and genetic testing is increasingly performed in individuals with these diagnoses to inform prognosis, refine management and provide information about recurrence risk in the family. For neurogenetic conditions associated with intellectual disability and ASD, data on natural history in adults are scarce; however, as older adults with these disorders are identified, it is becoming clear that some conditions are associated with both neurodevelopmental problems and neurodegeneration. Moreover, emerging evidence indicates that some neurogenetic conditions associated primarily with neurodegeneration also affect neurodevelopment. In this Perspective, we discuss examples of diseases that have developmental and degenerative overlap. We propose that neurogenetic disorders should be studied continually across the lifespan to understand the roles of the affected genes in brain development and maintenance, and to inform strategies for treatment.Cerebral small vessel disease (cSVD) is a leading cause of ischaemic and haemorrhagic stroke and a major contributor to dementia. Covert cSVD, which is detectable with brain MRI but does not manifest as clinical stroke, is highly prevalent in the general population, particularly with increasing age. Advances in technologies and collaborative work have led to substantial progress in the identification of common genetic variants that are associated with cSVD-related stroke (ischaemic and haemorrhagic) and MRI-defined covert cSVD. In this Review, we provide an overview of collaborative studies - mostly genome-wide association studies (GWAS) - that have identified >50 independent genetic loci associated with the risk of cSVD. We describe how these associations have provided novel insights into the biological mechanisms involved in cSVD, revealed patterns of shared genetic variation across cSVD traits, and shed new light on the continuum between rare, monogenic and common, multifactorial cSVD. We consider how GWAS summary statistics have been leveraged for Mendelian randomization studies to explore causal pathways in cSVD and provide genetic evidence for drug effects, and how the combination of findings from GWAS with gene expression resources and drug target databases has enabled identification of putative causal genes and provided proof-of-concept for drug repositioning potential. We also discuss opportunities for polygenic risk prediction, multi-ancestry approaches and integration with other omics data.During conversation, people take turns speaking by rapidly responding to their partners while simultaneously avoiding interruption1,2. Such interactions display a remarkable degree of coordination, as gaps between turns are typically about 200 milliseconds3-approximately the duration of an eyeblink4. These latencies are considerably shorter than those observed in simple word-production tasks, which indicates that speakers often plan their responses while listening to their partners2. Although a distributed network of brain regions has been implicated in speech planning5-9, the neural dynamics underlying the specific preparatory processes that enable rapid turn-taking are poorly understood. Here we use intracranial electrocorticography to precisely measure neural activity as participants perform interactive tasks, and we observe a functionally and anatomically distinct class of planning-related cortical dynamics. We localize these responses to a frontotemporal circuit centred on the language-critical caudal inferior frontal cortex10 (Broca's region) and the caudal middle frontal gyrus-a region not normally implicated in speech planning11-13. Using a series of motor tasks, we then show that this planning network is more active when preparing speech as opposed to non-linguistic actions. Finally, we delineate planning-related circuitry during natural conversation that is nearly identical to the network mapped with our interactive tasks, and we find this circuit to be most active before participant speech during unconstrained turn-taking. Therefore, we have identified a speech planning network that is central to natural language generation during social interaction.Gram-negative bacteria are responsible for an increasing number of deaths caused by antibiotic-resistant infections1,2. The bacterial natural product colistin is considered the last line of defence against a number of Gram-negative pathogens. The recent global spread of the plasmid-borne mobilized colistin-resistance gene mcr-1 (phosphoethanolamine transferase) threatens the usefulness of colistin3. Bacteria-derived antibiotics often appear in nature as collections of similar structures that are encoded by evolutionarily related biosynthetic gene clusters. This structural diversity is, at least in part, expected to be a response to the development of natural resistance, which often mechanistically mimics clinical resistance. Here we propose that a solution to mcr-1-mediated resistance might have evolved among naturally occurring colistin congeners. Bioinformatic analysis of sequenced bacterial genomes identified a biosynthetic gene cluster that was predicted to encode a structurally divergent colistin congener. Chemical synthesis of this structure produced macolacin, which is active against Gram-negative pathogens expressing mcr-1 and intrinsically resistant pathogens with chromosomally encoded phosphoethanolamine transferase genes. These Gram-negative bacteria include extensively drug-resistant Acinetobacter baumannii and intrinsically colistin-resistant Neisseria gonorrhoeae, which, owing to a lack of effective treatment options, are considered among the highest level threat pathogens4. In a mouse neutropenic infection model, a biphenyl analogue of macolacin proved to be effective against extensively drug-resistant A. baumannii with colistin-resistance, thus providing a naturally inspired and easily produced therapeutic lead for overcoming colistin-resistant pathogens.Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics1. Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two β-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development.The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has a central role in non-hom*ologous end joining, one of the two main pathways that detect and repair DNA double-strand breaks (DSBs) in humans1,2. DNA-PKcs is of great importance in repairing pathological DSBs, making DNA-PKcs inhibitors attractive therapeutic agents for cancer in combination with DSB-inducing radiotherapy and chemotherapy3. Many of the selective inhibitors of DNA-PKcs that have been developed exhibit potential as treatment for various cancers4. Here we report cryo-electron microscopy (cryo-EM) structures of human DNA-PKcs natively purified from HeLa cell nuclear extracts, in complex with adenosine-5'-(γ-thio)-triphosphate (ATPγS) and four inhibitors (wortmannin, NU7441, AZD7648 and M3814), including drug candidates undergoing clinical trials. The structures reveal molecular details of ATP binding at the active site before catalysis and provide insights into the modes of action and specificities of the competitive inhibitors. Of note, binding of the ligands causes movement of the PIKK regulatory domain (PRD), revealing a connection between the p-loop and PRD conformations. Electrophoretic mobility shift assay and cryo-EM studies on the DNA-dependent protein kinase holoenzyme further show that ligand binding does not have a negative allosteric or inhibitory effect on assembly of the holoenzyme complex and that inhibitors function through direct competition with ATP. Overall, the structures described in this study should greatly assist future efforts in rational drug design targeting DNA-PKcs, demonstrating the potential of cryo-EM in structure-guided drug development for large and challenging targets.The Drosophila brain is a frequently used model in neuroscience. Single-cell transcriptome analysis1-6, three-dimensional morphological classification7 and electron microscopy mapping of the connectome8,9 have revealed an immense diversity of neuronal and glial cell types that underlie an array of functional and behavioural traits in the fly. The identities of these cell types are controlled by gene regulatory networks (GRNs), involving combinations of transcription factors that bind to genomic enhancers to regulate their target genes. Here, to characterize GRNs at the cell-type level in the fly brain, we profiled the chromatin accessibility of 240,919 single cells spanning 9 developmental timepoints and integrated these data with single-cell transcriptomes. We identify more than 95,000 regulatory regions that are used in different neuronal cell types, of which 70,000 are linked to developmental trajectories involving neurogenesis, reprogramming and maturation. For 40 cell types, uniquely accessible regions were associated with their expressed transcription factors and downstream target genes through a combination of motif discovery, network inference and deep learning, creating enhancer GRNs. The enhancer architectures revealed by DeepFlyBrain lead to a better understanding of neuronal regulatory diversity and can be used to design genetic driver lines for cell types at specific timepoints, facilitating their characterization and manipulation.Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.The dominance of interactions over kinetic energy lies at the heart of strongly correlated quantum matter, from fractional quantum Hall liquids1, to atoms in optical lattices2 and twisted bilayer graphene3. Crystalline phases often compete with correlated quantum liquids, and transitions between them occur when the energy cost of forming a density wave approaches zero. A prime example occurs for electrons in high-strength magnetic fields, where the instability of quantum Hall liquids towards a Wigner crystal4-9 is heralded by a roton-like softening of density modulations at the magnetic length7,10-12. Remarkably, interacting bosons in a gauge field are also expected to form analogous liquid and crystalline states13-21. However, combining interactions with strong synthetic magnetic fields has been a challenge for experiments on bosonic quantum gases18,21. Here we study the purely interaction-driven dynamics of a Landau gauge Bose-Einstein condensate22 in and near the lowest Landau level. link3 We observe a spontaneous crystallization driven by condensation of magneto-rotons7,10, excitations visible as density modulations at the magnetic length. Increasing the cloud density smoothly connects this behaviour to a quantum version of the Kelvin-Helmholtz hydrodynamic instability, driven by the sheared internal flow profile of the rapidly rotating condensate. At long times the condensate self-organizes into a persistent array of droplets separated by vortex streets, which are stabilized by a balance of interactions and effective magnetic forces.Stellar ejecta gradually enrich the gas out of which subsequent stars form, making the least chemically enriched stellar systems direct fossils of structures formed in the early Universe1. Although a few hundred stars with metal content below 1,000th of the solar iron content are known in the Galaxy2-4, none of them inhabit globular clusters, some of the oldest known stellar structures. These show metal content of at least approximately 0.2% of the solar metallicity [Formula see text]. This metallicity floor appears universal5,6, and it has been proposed that protogalaxies that merged into the galaxies we observe today were simply not massive enough to form clusters that survived to the present day7. Here we report observations of a stellar stream, C-19, whose metallicity is less than 0.05% of the solar metallicity [Formula see text]. The low metallicity dispersion and the chemical abundances of the C-19 stars show that this stream is the tidal remnant of the most metal-poor globular cluster ever discovered, and is significantly below the purported metallicity floor clusters with significantly lower metallicities than observed today existed in the past and contributed their stars to the Milky Way halo.Magnetic fields have an important role in the evolution of interstellar medium and star formation1,2. As the only direct probe of interstellar field strength, credible Zeeman measurements remain sparse owing to the lack of suitable Zeeman probes, particularly for cold, molecular gas3. Here we report the detection of a magnetic field of +3.8 ± 0.3 microgauss through the H I narrow self-absorption (HINSA)4,5 towards L15446,7-a well-studied prototypical prestellar core in an early transition between starless and protostellar phases8-10 characterized by a high central number density11 and a low central temperature12. A combined analysis of the Zeeman measurements of quasar H I absorption, H I emission, OH emission and HINSA reveals a coherent magnetic field from the atomic cold neutral medium (CNM) to the molecular envelope. The molecular envelope traced by the HINSA is found to be magnetically supercritical, with a field strength comparable to that of the surrounding diffuse, magnetically subcritical CNM despite a large increase in density. The reduction of the magnetic flux relative to the mass, which is necessary for star formation, thus seems to have already happened during the transition from the diffuse CNM to the molecular gas traced by the HINSA. This is earlier than envisioned in the classical picture where magnetically supercritical cores capable of collapsing into stars form out of magnetically subcritical envelopes13,14.The 660-kilometre seismic discontinuity is the boundary between the Earth's lower mantle and transition zone and is commonly interpreted as being due to the dissociation of ringwoodite to bridgmanite plus ferropericlase (post-spinel transition)1-3. A distinct feature of the 660-kilometre discontinuity is its depression to 750 kilometres beneath subduction zones4-10. However, in situ X-ray diffraction studies using multi-anvil techniques have demonstrated negative but gentle Clapeyron slopes (that is, the ratio between pressure and temperature changes) of the post-spinel transition that do not allow a significant depression11-13. On the other hand, conventional high-pressure experiments face difficulties in accurate phase identification due to inevitable pressure changes during heating and the persistent presence of metastable phases1,3. Here we determine the post-spinel and akimotoite-bridgmanite transition boundaries by multi-anvil experiments using in situ X-ray diffraction, with the boundaries strictly based on the definition of phase equilibrium. link2 The post-spinel boundary has almost no temperature dependence, whereas the akimotoite-bridgmanite transition has a very steep negative boundary slope at temperatures lower than ambient mantle geotherms. The large depressions of the 660-kilometre discontinuity in cold subduction zones are thus interpreted as the akimotoite-bridgmanite transition. The steep negative boundary of the akimotoite-bridgmanite transition will cause slab stagnation (a stalling of the slab's descent) due to significant upward buoyancy14,15.Superconductivity is a remarkably widespread phenomenon that is observed in most metals cooled to very low temperatures. The ubiquity of such conventional superconductors, and the wide range of associated critical temperatures, is readily understood in terms of the well-known Bardeen-Cooper-Schrieffer theory. Occasionally, however, unconventional superconductors are found, such as the iron-based materials, which extend and defy this understanding in unexpected ways. In the case of the iron-based superconductors, this includes the different ways in which the presence of multiple atomic orbitals can manifest in unconventional superconductivity, giving rise to a rich landscape of gap structures that share the same dominant pairing mechanism. In addition, these materials have also led to insights into the unusual metallic state governed by the Hund's interaction, the control and mechanisms of electronic nematicity, the impact of magnetic fluctuations and quantum criticality, and the importance of topology in correlated states. Over the fourteen years since their discovery, iron-based superconductors have proven to be a testing ground for the development of novel experimental tools and theoretical approaches, both of which have extensively influenced the wider field of quantum materials.
Different pathogens can cause community-acquired pneumonia (CAP); however, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has re-emphasized the vital role of respiratory viruses as a cause of CAP. link3 The aim was to explore differences in metabolic profile, body composition, physical capacity, and inflammation between patients hospitalized with CAP caused by different etiology.

A prospective study of Danish patients hospitalized with CAP caused by SARS-CoV-2, influenza, or bacteria. Fat (FM) and fat-free mass (FFM) were assessed with bioelectrical impedance analysis. Physical activity and capacity were assessed using questionnaires and handgrip strength. Plasma (p)-glucose, p-lipids, hemoglobin A1c (HbA1c), p-adiponectin, and cytokines were measured.

Among 164 patients with CAP, etiology did not affect admission levels of glucose, HbA1c, adiponectin, or lipids. Overall, 15.2% had known diabetes, 6.1% had undiagnosed diabetes, 51.3% had pre-ry response in patients with COVID-19, metabolic profile, body composition, and physical capacity were similar to patients with influenza and bacterial CAP.
Despite higher inflammatory response in patients with COVID-19, metabolic profile, body composition, and physical capacity were similar to patients with influenza and bacterial CAP.
Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study's objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP.

SPIRIT was a randomized trial of adults with overweight or obesity. Participants were randomized to one of three arms metformin treatment, coach-directed behavioral weight loss on a DASH diet, or self-directed care (control). Of 121 participants, a random subset (n = 88) was selected to have LBP measured at baseline, 6 months, and 12 months post intervention. Intervention effects on LBP over time were assessed using generalized estimating equations (GEE). We also examined whether the intervention effects were modified by change in diet and weight.

Arms were balanced by sex (83% female), race (51% white), and age (mean 60 years), with no differences in baseline LBP (median 4.