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Sequence analysis of the Spike, nsp12 (RNA-dependent RNA polymerase), nsp3 (PLpro), a...
Mohamad Hakim
* Gunadi

Mohamad Hakim

and 19 more

May 10, 2023
During the Covid-19 pandemic, the resurgence of SARS-CoV-2 was due to the development of novel variants of concern (VOC). Thus, genomic surveillance is essential to monitor continuing evolution of SARS-CoV-2 and to track the emergence of novel variants. In this study, we performed phylogenetic, mutation, and selection pressure analyses of the Spike, nsp12, nsp3, and nsp5 genes of SARS-CoV-2 isolates circulating in Yogyakarta and Central Java provinces, Indonesia from May 2021 to February 2022. Various bioinformatics tools were employed to investigate the evolutionary dynamics of distinct SARS-CoV-2 isolates. During the study period, 213 and 139 isolates of Omicron and Delta variants were identified, respectively. Particularly in the Spike gene, mutations were significantly more abundant in Omicron than in Delta variants. Consistently, in all of four genes studied, the substitution rates of Omicron were higher than that of Delta variants, especially in the Spike and nsp12 genes. In addition, selective pressure analysis revealed several sites that were positively selected in particular genes, implying that these sites were functionally essential for virus evolution. In conclusion, our study demonstrated a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia.
Capercaillie Tetrao urogallus relocation after increased disturbance along woodland t...
Robert Moss
Fiona Leckie

Robert Moss

and 3 more

May 10, 2023
Wild vertebrates usually avoid ground disturbed by humans but consequences for their distribution and density are uncertain. The local distribution of capercaillie shifted after an increase in disturbance along woodland tracks adjacent to an expanding Scottish village. We surveyed the birds’ droppings before and after the building of 30 new houses, and model the probability of finding droppings (Pf) in relation to period plus two disturbance gradients – distance to a much disturbed ‘entry zone’ by the village (dE) and ‘distance to nearest track’ (dT). Estimates of Pf are benchmarked to average Pf (Pfav) – a notional scenario in which the birds’ distribution is unaffected by tracks. Change between periods occurred mainly on a strip of ground centred on tracks and averaging 80 m wide, where Pf fell from about 0.5 Pfav before the development to 0.2 Pfav after it. By contrast, Pf on ground 120–260 m from tracks, under a third of the 273 ha main study area, remained at about 3 Pfav throughout the study – indicating a net influx of capercaillie displaced from ground beside tracks in both periods. No capercaillie droppings were found in the entry zone. Beyond this zone, throughout the study, Pf increased as tracks sparsened until dE approached 400 m – whereupon track density and Pf steadied together. Beyond 400 m, Pf remained depressed on ground near tracks (dT ⪅ 100 m). New desire paths after the development caused the proportion of ground where dT < 100 m to increase slightly, from 56% to 60%. Birds on roughly half of a 50 ha refuge should be undisturbed by direct effects of track-based activities – but, if increases in density caused by displaced birds are also deemed disturbance, a refuge would need to be over 3 km2 to keep half of it undisturbed.
Functional endemism captures hotspots of unique phenotypes and restricted ranges
Alexander Skeels
Keaghan Yaxley

Alexander Skeels

and 1 more

May 10, 2023
# There is no abstract for a Brevia article Endemism is a measure of geographic range restriction which is used to highlight regions with unique biota, found nowhere else on earth. Here, we develop a trait-based metric for a functional approach to endemism studies - functional endemism - and explore global patterns in birds. We find that the world’s islands and mountain ranges are hotspots of functional endemism in birds, highlighting the importance of these ecosystems for conservation.
Divergent driving mechanisms of community temporal stability in drylands of China
Kai Wang
Cong Wang

Kai Wang

and 7 more

May 10, 2023
Climate change and human activities are changing the structure and function of dryland ecosystems at unprecedented rate, thus threatening the stability of ecosystems. The stability of dryland ecosystems is vital for ecological security and local livelihoods. However, the mechanisms that underlie ecosystem stability in drylands remain uncertain due to limited field data from regional studies. Combined with transect survey in the drylands of China along the aridity gradient and remote sensing data, we characterized community temporal stability and identified its driving mechanisms along the aridity gradient. The results showed the community temporal stability in drylands of China revealed a U-shaped curve with increasing aridity and its major driving mechanisms shifted at an aridity level of ~0.88. In regions where aridity is below 0.88, increasing precipitation and species richness resulted in higher community productivity and community stability. In regions where aridity is above 0.88, however, higher soil organic carbon content and species richness may lead to higher variability of community productivity and lower ecosystem stability. Overall, our findings revealed that there existed an aridity threshold leading to abrupt changes on community stability in drylands of China. Our study also suggested divergent driving mechanisms of community stability above and below the threshold, which should be considered in policy making regarding the ecosystem management of drylands.
Protective effects of SS-31 on Post-Contrast Acute Kidney Injury in Diabetes Mice
jingyi hu
ziqian wu

jingyi hu

and 7 more

May 10, 2023
Post-contrast acute kidney injury (PC-AKI) has emerged as the third leading cause of iatrogenic acute renal failure. Diabetes mellitus not only represents an independent risk factor for PC-AKI but also remains a major cause of chronic kidney disease (CKD). SS-31, an antioxidant peptide targeting mitochondria, is a potential preventive drug for PC-AKI. In this study, we established a PC-AKI model by injecting iodixanol in type 1 diabetic mice. Blood and tissue samples were collected to confirm that iodine injection caused excessive reactive oxygen species (ROS) in the kidney, activated the NLRP3 inflammasome pathway, and subsequently aggravated the development of PC-AKI. We also confirmed that SS-31 can reduce acute kidney injury induced by iodine contrast agent in diabetes by protecting mitochondrial function and inhibiting the ROS-NLRP3 signaling pathway.
Sparus Docking Station: A Current Aware Docking Station For a Non-holonomic AUV
Joan Esteba
Patryk Cieslak

Joan Esteba

and 3 more

May 10, 2023
This paper presents the design and development of a funnel-shaped Sparus Docking Station (SDS) intended for the non-holonomic torpedo-shaped Sparus II Autonomous Underwater Vehicles (AUV). The SDS is equipped with sensors and batteries, allowing for a stand-alone long-term deployment of the AUV. An inverted Ultra Short BaseLine (USBL) system is used to locate the Docking Station (DS) as well as to provide long-term drift-less AUV navigation. The SDS is able to observe the ocean currents using a Doppler Velocity Log (DVL), being motorized to allow its self-alignment with the current. Moreover, a docking algorithm accounting for the current is used to guide the robot during the docking maneuver. The paper reports experimental results of the docking maneuver in sea trials.
Waiting for the next winter. Outpatient pediatric visits for respiratory infections b...

Paula Gonzalez Pania

and 3 more

May 11, 2023
IntroductionAcute lower respiratory infections (ALRIs) are the main cause of illness and hospitalization in children, and their most frequent etiology is viral (1). During the COVID-19 pandemic, a decrease in pediatric visits for respiratory causes was observed (2,3), probably because the nonpharmacological mitigation measures used to face the pandemic altered the circulation of the most common respiratory viruses.However, many of the reports refer to a specific disease (bronchiolitis) or to a particular virus (respiratory syncytial virus (RSV) and influenza), include data from one or a few centers, or refer to hospitalized patients (4,5,6). In contrast, there is little information on the magnitude of this phenomenon in larger populations, especially in relation to less seriously affected patients, who tend to be the majority in the case of ALRIs. Unfortunately, recording the reasons for health facility visit due to ALRIs can be confusing (7). Despite the different coding systems used, there is still difficulty in identifying ALRI-related visits (8). We recently developed an algorithm that showed acceptable precision in the identification of ALRI-related visits in electronic health records, based not only on the reasons for consultation or identified diseases but also on terms used by professionals in the text of the registry (9). The public health system of the City of Buenos Aires has electronic health records for ambulatory care areas before the pandemic, allowing a precise evaluation of the impact of the pandemic on outpatient visits for different causes in a large urban population.Our objective was to evaluate the impact of the COVID-19 pandemic on outpatient visits for acute lower respiratory infections in the city of Buenos Aires.MethodsThis was an observational study that included all visits at health facilities of the public health system of the City of Buenos Aires (Gobierno de la Ciudad de Buenos Aires - GCABA) for children under 2 years of age, registered in the GCABA electronic health records, between January 1, 2018, and December 31, 2022. The visits occurred at one of the hospitals or primary care centers of the system (10).To identify the visits in the GCABA health database, a validated algorithm was (9).The total number of visits and ALRIs-related visits and their distribution throughout the study period, by year and by season (cold months - autumn/winter: April, May, June, July, August and September -, and warm months - spring/summer: October, November, December, January, February and March) were evaluated.The proportion of ALRIs-related visits was calculated (percentage with 95% CI). The proportion of ALRIs-related visits was compared between different years (chi square for trend) and seasons (chi square). The analysis was carried out using IBM-SSPS Statistics 22.0. Data were conveniently anonymized. Approval by the Institutional Ethics Committee was requested and obtained (GCABA public research registry number 7141/2022).Results In the period under study, 704,426 outpatient visits were registered for children under 2 years of age in hospitals and primary care centers of the GCABA. The average age of the patients was 0.8 ± 0.5 months, and 48% were male. Of the total number of visits, 51,975 (7.38%; 95% CI 7.32-7.44) were ALRIs-related. The total number of visits, particularly those ALRIs-related, decreased significantly during 2020 (Table 1). In general, the proportion of ALRIs-related visits was significantly higher in cold months than in warm months (9.8% vs. 5.5%; OR: 1.76 95% CI: 1.73-1.79; p <0.001). This distribution was clearly observed before (2018, 2019) and after the pandemic (2022); during 2020, it was reversed (more ALRI in warm months), and in 2021, no difference was observed (Table 2). A peak of ALRI-related visits occurred in the cold-month period in the prepandemic years (2018-2019); there was no peak in 2020; and the peak was delayed in 2021, with a recovery of prepandemic seasonality in 2022 (Figure 1). Visits for ALRIs decreased after the institution of mobility restrictions (March 2020) and increased again when the restrictions decreased, in particular with the return to full school attendance (July 2021) (Figure 1).Discussion In countries with a temperate climate, ALRIs usually have a seasonal pattern with an increase in cold months, following the circulation of the main viruses responsible for such infections (RSV and influenza virus); this pattern is observed both in the Northern Hemisphere and in the Southern Hemisphere (11,12). In our study, in 2018 and 2019, we verified this pattern in the city of Buenos Aires, with cases of ALRI appearing in the cold months and peaking in June, the beginning of the southern winter. During the first year of the COVID-19 pandemic, a drastic decrease was observed in health visits in general, and in visits for respiratory infections in particular, for the pediatric population around the world (13,14). This decrease was fundamentally attributed to the nonpharmacological mitigation measures that adopted to reduce the risk of SARS-CoV-2 infection: the use of face masks, frequent hand washing and social distancing measures, including school closings and public circulation limitations (15). In this study, in 2020, the number of cases of ALRIs decreased after the establishment of a national-wide lockdown at the end of the summer (16), remaining very low during the rest of the year, without showing a characteristic winter peak. This phenomenon is similar to that reported in other countries in the Southern Hemisphere, such as Brazil (17) and Australia (18), where there was a decrease in cases of bronchiolitis and hospitalizations for respiratory causes among the pediatric population in that period. In the Northern Hemisphere, during the first pandemic winter (2020-2021) and with mitigation measures still in force, similar findings were described: in cities in northern Italy (19) and in England (20), a decrease was observed in the number of pediatric hospitalizations and, particularly, in the incidence of RSV bronchiolitis between October 2020 and March 2021. During 2021, mitigation measures gradually decreased, and the circulation of common respiratory viruses reappeared (21). In this study, the cases of ALRIs increased in winter 2021 but later and with a somewhat lower intensity than in the prepandemic years (2018-2019). This phenomenon was also reported in relation to cases of RSV infection in pediatric hospitals in Buenos Aires (22,23). A similar delay in the onset of respiratory infections was observed in the Northern Hemisphere in the winter of 2021-2022 (24,25). In 2022, the winter increase in ALRIs cases occurred earlier and with greater intensity than in 2021, approaching prepandemic values. Something similar was observed in the Northern Hemisphere (2022-2023), with the seasonal cycle of RSV circulation moving toward prepandemic patterns (25). As mentioned above, most of the studies on the impact of the pandemic on pediatric respiratory infections include hospitalized patients and/or those affected by RSV or influenza. As the spectrum of viruses responsible for ALRIs in outpatients may be different (including rhinoviruses and parainfluenza viruses) (26), the impact could have been different in these patients. However, our study, which included only outpatient visits, showed similar results, indicating that the impact of the pandemic was similar for all viruses responsible for ALRIs. During the pandemic, the circulation of respiratory viruses was greatly altered, and there were questions regarding whether the usual pattern would re-emerge (27). This study provides evidence that a return to the usual seasonal patterns of viral circulation is occurring. The pandemic highlighted, on several occasions, the need to be prudent in forecasting. In particular, children were affected by the pandemic in an indirect way (not related to the SARS-Cov2 virus) but to a much greater extent (domestic violence, eating disorders, anxiety, etc.) (28). Although there is a return of the circulation of common respiratory viruses to prepandemic patterns, it is unknown whether the immunological debt (29) of children has been fully settled or if a different pattern will emerge next winter. ConclusionOutpatient visits for ALRIs decreased significantly in the city of Buenos Aires during the COVID-19 pandemic and currently seem to have recovered their magnitude and seasonality.
New prediction categories in CASP15
Andriy Kryshtafovych
Maciej Antczak

Andriy Kryshtafovych

and 16 more

May 10, 2023
Prediction categories in the Critical Assessment of Structure Prediction (CASP) experiments change with the need to address specific problems in structure modeling. In CASP15, four new prediction categories were introduced: RNA structure, ligand-protein complexes, accuracy of oligomeric structures and their interfaces, and ensembles of alternative conformations. This paper lists technical specifications for these categories and describes their integration in the CASP data management system.
Is structural variation necessary to create islands of divergence in moderate gene fl...
Peter Euclide
Wes Larson

Peter Euclide

and 6 more

May 10, 2023
Local adaptation is often facilitated by loci clustered in relatively few regions of the genome, termed genomic islands of divergence. However, the mechanisms that create, mold, and maintain these islands are poorly understood. Here, we use sockeye salmon as a model species to investigate the mechanisms responsible for creating islands of divergence linked to adaptive variation. Previous research suggests that multiple islands are involved in adaptive radiation of sockeye salmon. However, these studies were based on low-density genomic methods that genotyped tens to thousands of loci, making it difficult to elucidate the mechanisms responsible for islands. We used whole genome resequencing to genotype millions of loci to investigate these mechanisms. We discovered 64 islands, 16 of which were shared between two isolated populations; these 16 islands were clustered in four genomic regions. Characterization of the shared regions suggested that three of four were likely created by chromosomal inversions, while the other was created by processes not involving structural variation. Additionally, all four regions were relatively small (< 600 kb), suggesting inversions and other low recombination regions do not have to span megabases to be important for adaptive divergence. In sum, our study demonstrates that heterogeneous selection can lead to a mosaic of islands created by different mechanisms within the same genome. Future studies should continue to investigate how gene flow, selection, and the architecture of genetic traits interact to influence the genomic landscape of adaptive divergence.
Safety of SARS-CoV-2 vaccine in patients with autoimmune neurological conditions: a s...
Fan Ning
Xiang-qi Cao

Fan Ning

and 5 more

May 10, 2023
Risk of adverse effects and exacerbation in autoimmune neurological conditions(ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. We selected studies that provided data on the occurrence of adverse effects and exacerbation of conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine were estimated. Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27–0.43, I 2= 100%). The pooled incidence rate of exacerbation adverse events was 0.05(95%CI, 0.04-0.07, I 2 = 84%). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18–0.36, I 2 = 98%), 0.16(0.11-0.21, I 2 = 93%), 0.15(0.00-0.31, I 2 = 97%), 0.13(0.08-0.19, I 2 = 97%), 0.11(0.07-0.15, I 2 = 95%), 0.11(0.07-0.16, I 2 = 97%), and0.09(0.03-0.16, I 2 = 96%), respectively. According to available evidence, the administration of COVID-19 vaccines in individuals with ANC seems to be well-tolerated, with few reports of adverse events. Furthermore, exacerbation of ANC following vaccination appears to be infrequent.
SPATIAL DISTRIBUTION AND LANDSCAPE IMPACT ANALYSIS OF QUARRIES IN A HIGHLY FRAGMENTED...
Irati Carabia-Sanz
María V. Simoy

Irati Carabia-Sanz

and 4 more

May 10, 2023
Mining activity generates significant changes in the ecosystems in which it takes place, affecting the atmosphere and the surrounding aquatic and terrestrial systems, causing the destruction of landscapes, the loss of vegetation, and altering native environments. As it is an impact associated with increasing urbanization and population growth, the area occupied by quarries has increased worldwide. In the province of Buenos Aires, quarries are often abandoned without any remediation, leading to further deterioration of the ecosystem. This work aims to analyze quarrying activity’s spatiotemporal effect on the Pampean grassland in the Tandilia mountains (Buenos Aires province, Argentina). Based on Landsat 5, 7, and 8 satellite imagery, from 1996 to the present, and using QGIS software, we identified the location and extension of quarries, and we analyzed their evolution through time. Quarries currently occupy an area of 6428 ha, which was originally part of the Pampean grassland. The number of open quarries increased by 129%, from 69 in 1996 to 158 in 2022, and the area used for this activity increased by 172%, with a greater expansion being detected in the last ten years. These results conclude that this extractive activity represents a major threat to the Pampean grassland with the consequent loss of biodiversity and invasion of exotic plants capable of colonizing areas altered by human activity.
Broadly neutralizing anti- HIV-1 antibodies do not inhibit HIV-1 Env-mediated cell-ce...
Nejat Düzgüneş
Michael Yee

Nejat Düzgüneş

and 2 more

May 10, 2023
Broadly neutralizing anti- HIV-1 antibodies do not inhibit HIV-1 Env-mediated cell-cell fusionNejat Düzgüneş*, Michael Yee and Deborah ChauDepartment of Biomedical Sciences, Arthur A. Dugoni School of DentistryUniversity of the Pacific, 155 Fifth StreetSan Francisco, CA 94103, USA
A Comparative Analysis of Agronomic Water-Use Efficiency and its Proxy Measures as de...
L.V.Y. Weerarathne
Z. Jahufer

L.V.Y. Weerarathne

and 4 more

May 10, 2023
Water-use efficiency (WUE) is an under-researched but very important drought tolerance trait for forage breeding purposes. This research evaluated morpho-physiological traits linked to agronomic water-use efficiency (WUE A) and its proxy measures based on δ 13C (WUE i) or gas exchange (evapotranspiration, WUE AET, or stomatal conductance WUE ASC) and their quantitative genetic parameters (QGPs) of 400 half-sib family genotypes of Lolium perenne L. (PRG) in a 5-month soil drought cycle spanning field capacity (FC), 85–90% FC, 55–65% FC, 45–55% FC, and <55% FC (post-cutting regrowth). Principal component analysis (PCA) of trait data distinguished a group of PRG genotypes where high WUE A and pasture yield were associated with a distinctive deep rooting pattern and improved leaf hydration at more negative leaf osmotic and water potentials. Plants with this trait association sustained net assimilation and soil moisture reserves throughout the drought cycle. Estimated QGPs including high narrow-sense heritability ( h n 2 > 0 . 7 ; p < 0 . 05 ) of key traits emphasized the genetic potential of the identified trait combination for selecting PRG for improved drought tolerance. PCA and estimates of QGPs revealed a weak association between WUE A, WUEi, WUE ASC, or WUE AET under the conditions tested. The results highlight the preferability of WUE A over its proxy measures in defining PRG drought tolerance.
Data-driven adaptive trajectory tracking control of unmanned marine vehicles under di...
Li-Ying Hao
Huiying Liu

Li-Ying Hao

and 3 more

May 10, 2023
This article researches the trajectory tracking problem for unmanned marine vehicles (UMVs) with disturbances and under denial-of-services (DoS) attacks in the wireless channel. By applying the partial form dynamic linearization algorithm, an equivalent data-driven model of the UMVs with ocean disturbances is firstly established. And the disturbances are estimated by using extended state observer, which improves the immunity of the UMVs to disturbances in the environment, and the robustness of the UMVs systems is better. It is the first time that the DoS attacks are considered under the data model for UMVs, and a novel data-driven adaptive trajectory tracking control framework is constructed. When the proposed equivalent data model suffers from DoS attacks which follows the Bernoulli distribution, an attack predictive compensation mechanism is devised to relieve the influence of DoS attacks. Based on it, the data-driven adaptive trajectory tracking controller is designed such that the error of trajectory tracking is convergent under DoS attacks and external disturbances. Finally, the effectiveness of the proposed data-driven control scheme and the predictive compensation mechanism is validated through the simulations.
Effects of Comorbidities on Hospitalization Costs of COVID-19 in Turkey
Nehir Balcı
Hakan Özkaya

Nehir Balcı

and 5 more

May 10, 2023
Background: In December 2019, pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. Its effects on the national and global economies have been tremendous. There is limited evidence on treatment costs and effects of comorbidities on treatment costs, which are crucial inputs for policymakers. Objective: The main objective of this study is to retrospectively determine the direct costs of hospitalization due to COVID-19 treatment and their association with comorbidities. Methods: This is a retrospective study conducted at two prominent research and training hospitals in İzmir, Turkey during the first year of the COVID-19 pandemic. First hospitalization costs of 2,067 patients with COVID-19 were analyzed. Second association of comorbidities with hospitalization costs of 532 patients with COVID-19 was estimated. Results: Analyses based on the whole sample of 2,067 patients showed that the average hospitalization cost was $1,432.3 (PPP $4,994.7). Treatment cost is higher for male patients and increases with age and intensive care unit admissions. The average length of hospitalization was 10.6 days (SD=8.5) and the average length of ICU hospitalization was 9.9 (SD=9.6). The average daily hospitalization cost was $135.25 (PPP $471.63). Analyses showed that sex, age, intensive care unit hospitalization, myocardial infarction, cerebrovascular and transient ischemic attacks, chronic obstructive pulmonary disease and chronic kidney disease were found significantly associated with hospitalization costs. Conclusion: COVID-19 is a novel pandemic that causes morbidity and mortality at considerable levels. A holistic approach to fight the pandemic requires unraveling not only medical but also financial aspects.
Spiro-isoxazolonechromans-3 alleviates LPS-induced acute lung injury in mice via inhi...
Yunhui Zhang
Baoping Xiong

Yunhui Zhang

and 9 more

May 10, 2023
Acute lung injury (ALI) is a serious clinical disease with a mortality rate of 30-40%. We designed and synthesized a structurally novel compound, Spiro-isoxazolonechromans-3 (SI-3), to seek a new approach for treating excessive inflammation in ALI. In the present study, we induced RAW 264.7 cells with LPS and injected LPS intraperitoneally in BALB/c mice to establish an ALI model. Molecular docking results showed SI-3 located in the hydrophobic pocket of Janus Kinase 1 (JAK1) and interacted with JAK1 through amino acid residue Leu959. SI-3 selectively inhibited the JAK1 enzyme activity with an IC50 of 9 nM and is non-toxic. In vitro, LPS-induced macrophage proliferation, activation, and secretion of inflammatory cytokines were inhibited by SI-3, which promoted macrophage apoptosis. In vivo, SI-3 improved the survival rate of ALI mice by reducing pathological lung injury and inflammatory response. Both in vivo and in vitro, we discovered that SI-3 exerted a downregulatory impact on the JAK1-STAT pathway according to the results of western-blot studies and showed the same effect in JAK1-overexpressing macrophages. Overall, SI-3 could reduce LPS-induced inflammatory response and promote macrophage apoptosis by inhibiting JAK1 kinase and affecting JAK1/JAK3-STAT pathway, resulting in significant anti-inflammatory effects, which alleviated the LPS-induced ALI in mice.
The Sensitization of The Transient Receptor Potential Vanilloid 1- Mediated Responses...
sara aldossary
mhammed alsalem

sara aldossary

and 2 more

May 10, 2023
Transient receptor potential vanilloid type-1 (TRPV1) channels play key roles in chronic pain conditions and are modulated by different inflammatory mediators to elicit heat sensitisation. Bradykinin is a 9-amino acid peptide chain that promotes inflammation. The aim of present study is to investigate how bradykinin and prostaglandin receptors (EP3 and EP4) modulate the sensitisation of TRPV1-mediated responses. Calcium imaging studies of rat dorsal root ganglion (DRG) neurons were employed to investigate the desensitizing responses of TRPV1 ion channels by capsaicin, and the re-sensitization of TRPV1 by bradykinin, then to explore the role EP3 and EP4 receptors in mediating these bradykinin-dependent effects. Immunocytochemistry was used to study the co-expression and distribution of EP4, TRPV1, COX-1 and B2 in rat DRG neurons. Desensitization was seen upon repeated capsaicin application, we show that bradykinin-mediated sensitization of capsaicin-evoked calcium responses in rat DRG neurons occurs is dependent on COX-1 activity, and utilises a pathway that invovles EP4 but not EP3 receptors. The present study provides evidence for a novel signalling pathway through which bradykinin can regulate the TRPV1 ion channel function via the EP4 but not EP3 receptors and provides the anatomical basis for this regulation
Genetic Polymorphisms of Carnosine Synthase -1(ATPGD1) and Serum Carnosine Levels in...
Haneen S. Shaheed
Shatha H. Ali

Haneen S. Shaheed

and 1 more

May 10, 2023
Diabetes mellitus (DM) is a metabolic disorder specified by persistent hyperglycemia that occurs when β-cell insulin production became unable to control blood glucose with deterioration of response for insulin. The consequent development of DM complications with increased risk for many diseases caused by damaged variety of biological systems, including blood vessels, eyes, kidneys, heart, and nerves. Carnosine is a natural dipeptide (β-alanyl-L-histidine) expressed in both the central nervous system and periphery, it occurs in several tissues most notably in muscle where they represent an appreciable fraction of the total water-soluble nitrogen-containing compounds. Carnosine is synthesized by a cytosolic amino acid ligase, carnosine synthase-1 (CARNS1; also known as ATP-grasp domain–containing protein 1, ATPGD1; EC 6.3.2.11).Several biological and physiological functions have been attributed to carnosine, such as being an anti-inflammatory and antioxidant agent, antiglycating actions, and as a modulator of mitochondrial metabolism. Carnosine level in human serum is affected by several enzymes like carnosine synthase-1 (responsible of carnosine synthesis),thus any genetic polymorphisms in these enzymes could have an impact on enzymes levels and therefore serum carnosine level with consequent increased risk for many diseases. This study was aimed to estimate the occurrence of Carnosine synthase -1 SNP (rs 1790733) on chromosom11 (intron –variant) in Iraqi type 2 diabetics with and without cardio vascular diseases and it’s correlation with serum levels of carnosine & carnosine synthase-1 and their association with CVD as T2DM complication. To achieve this aim Enzyme Linked Immunosorbent Assay (ELISA) specific kits were used to estimate serum levels of carnosine & carnosine synthase-1. High resolution melt technique (HRM) was applied for detecting gene polymorphism of carnosine synthase-1 gene (ATPGD1). The results showed that gene polymorphism of SNP (rs1790733) increased the chance of CVD in T2DM patients by 84.5% by its effect to decrease the mean of serum levels of carnosine by decreased carnosine synthase-1 level that may correlate to development of CVD in T2DM patients.
Seroprevalence of SARS-CoV-2 antibodies in the general population of Bamako, Mali, an...
Bourama  Traoré
Merepen  Guindo

Bourama Traoré

and 25 more

May 10, 2023
Background: The seroepidemiological characteristics of SARS-CoV-2 infection in Mali are not yet well understood. This study assessed SARS-CoV-2 antibody seroprevalence and factors associated with infection in the general population of Bamako, the capital city and epicenter of COVID-19, to determine the magnitude of the pandemic and contribute to control strategies improvement in Mali. Methods: A cross-sectional survey was conducted in September 2022 to collect data on sociodemographic information, clinical characteristics, comorbid factors, and blood samples. ELISA was performed to determine anti-Spike (S) and anti-RBD antibody levels, and RT-PCR to confirm SARS-CoV-2 infection in oropharyngeal swabs. A total of 3601 participants were enrolled in RedCap. Result: the mean age of participants was 33.5±15.9 years old; the sex ratio female: male was 3.6:1. The most representative were the 20–29 (28.9%, n=1043) and the 30–39 (26.9%, n=967) years-old. The COVID-19 vaccine coverage among the participants was 35.8%, with vaccines from Covidshield AstraZeneca (AZ, 13.4%), Johnson and Johnson (J&J, 16.7%), Sinovac (3.9%), and BioNTech Pfizer (1.8%). Overall, S protein and RBD antibodies seroprevalence was remarkably high in the general population (98% and 97%, respectively). Factors such as youth (1–9 years old) and male sex were associated with lower antibody responses against S and RBD, whereas previous exposure to patients with COVID-19 and receiving the COVID-19 vaccine were associated with increased odds of antibody responses. Conclusion: This serosurvey demonstrated the high seroprevalence of SARS-CoV-2 antibodies and highlighted the factors that may influence antibody responses, clearly underlining an underestimation of the pandemic in Mali.
Recurrent Staphylococcal Scalded Skin Syndrome in a 20 month old -- A case report
Camille Basurto
Kyla Berreth

Camille Basurto

and 2 more

May 10, 2023
Title: Recurrent Staphylococcal Scalded Skin Syndrome in a 20 month old – A case reportAuthors: Camille Basurto, M.S.1, Nada Baah-Owusu, M.D. 2, Kyla Berreth, D.O.2Institutional Affiliations: 1Liberty College of Osteopathic Medicine, 306 Liberty View Lane, Lynchburg, VA, 24502;2Sovah Pediatrics - Danville, 201 S. Main Street, Suite 2100, Danville, VA 24541Corresponding Author Present Address: 40 Glen Hill Road, Wilton, CT 06897Keywords: Staph scalded skin syndrome, exotoxins, Staphylococcus, toxic epidermal necrolysis, atopic dermatitisWord, Figure, reference count: 1406, 2, 13Conflict of Interest Statement: The authors have no disclosures to report.Consent statement: Patient’s guardians provided written consent for the use of patient photographs and related materials for publication.Abstract: We present a case of a 20 month old child with a history of atopic dermatitis that exhibited recurrent erythematous-bullous lesions consistent with Staphylococcal Scalded Skin syndrome (SSSS). SSSS is an exfoliative toxin mediated skin disorder most commonly found in children. In this paper, we discuss the importance of recognizing the clinical symptomatology and progressive nature of SSSS, particularly in patients with a history of atopic dermatitis, to assure prompt treatment and resolution of the syndrome.
Advances in the study of macrophage polarization in inflammatory immune skin diseases
Tingting Xia
Shengping Fu

Tingting Xia

and 10 more

May 10, 2023
In response to various microenvironmental stimuli, macrophages are highly plastic and primarily polarized into the pro-inflammatory M1-type and the anti-inflammatory M2-type, both of which perform almost entirely opposing functions. This characteristic determines that macrophages carry out various tasks during various stages of immunity and inflammation. An imbalance in the M1/M2 macrophage ratio is often observed in inflammatory immune skin diseases, and modulation of the macrophage polarization phenotype exacerbates or alleviates the associated symptoms. Therefore, this review presents the mechanisms of macrophage polarization, inflammation-related signaling pathways (JAK/STAT, NF-κB, PI3K/Akt) and the role of both in inflammatory immune skin diseases (psoriasis, AD, SLE, BD, etc.) with the aim of providing new directions for basic and clinical research of related diseases.
Nitrogen Budget Quantification Overview in the US
Yanyu Wang

Yanyu Wang

May 10, 2023
A document by Yanyu Wang. Click on the document to view its contents.
Recurrent Pyogenic Cholangitis
Narendra Pandit
Durga Neupane

Narendra Pandit

and 1 more

May 10, 2023
Recurrent Pyogenic CholangitisA 59-year-old South Asian female presented with the complain of pain upper abdomen and recurrent fever for one year. There was no history of vomiting, jaundice, anorexia or weight loss. Family history was unsupportive of diagnosis. On laboratory examination, alkaline phosphatase was elevated by two times. Serum bilirubin was normal and her leukocytes count was 11200/mm3. Rest of the systemic examination was normal. Contrast enhanced computed tomography(CECT) revealed multiple hypodense/hyperdense lesion in segment 3 of liver. Magnetic resonance imaging(MRI) showed hypo-hyperdense focal lesions with conglomerate appearance on segment 3 of liver suggestive of hepatolithiasis (Figure 1). Left lateral segmental resection (Figure 2) and intrahepatic choledochoscopy from dilated left hepatic duct and stone clearances was done. On histopathological examination, definitive diagnosis of recurrent pyogenic cholangitis was established with no evidence of malignancy. At a 3-year follow-up, the patient is free of recurrence.The incidence of hepatolithiasis is variable. It is highly prevalent in parts of Asia, such as China, Japan, and South Korea, with a reported incidence between 3.1% and 21.2%.1 However, with an incidence of about 1%, hepatolithiasis is rare in Western countries.The mechanism of development of hepatolithiasis is yet to be fully elucidated. Cholestasis, cholangitis, an anatomical abnormality of the bile ducts, abnormal bile metabolism, malnutrition, and low socio-economic status are significant risk factors for hepatolithiasis. According to several studies, indications of hepatectomy for hepatolithiasis include the following instances: (i ) unilobar hepatolithiasis, and particularly that on the left; (ii ) atrophy or severe fibrosis of the affected liver segments or lobe; (iii ) presence of a liver abscess; (iv ) cholangiocarcinoma; and (v ) multiple intrahepatic stones causing marked biliary stricture or dilation.2 Globalization, apart from changing the socioeconomic status of regions, has additionally altered disease dynamics globally. Hepatolithiasis, as a result of recurrent pyogenic cholangitis, although still rare, is becoming progressively evident in the West because of immigration from the Asia-Pacific region, where the disease is endemic. Such rare but emerging disease has imposed significant challenges to the physicians and surgeons. Uenishi et al.3 presented outcomes for 86 patients who underwent a hepatectomy from 1998 to 2012. Seventy-six patients (88%) had immediate stone clearance whereas 82 patients (95%) had final stone clearance.3 A multi-disciplinary team approach involving radiologists, internists, pathologists, oncologists, and surgeons is deemed necessary for the timely diagnosis and safe, affordable treatment, thus ensuring good prognosis to the patients.Low socio-economic status of our patient could have been the attributing factor. Also, unilobar hepatolithiasis, and particularly that on the left was the main indication for left lateral segmental hepatectomy in our case. With this image, we would like to recommend that the differential diagnosis of hepatolithiasis should be thought in the back of mind if an elderly person from endemic region presents with the complain of pain upper abdomen and recurrent fever. Surgical intervention is deemed necessary with the aforementioned indications and it can provide good prognosis to the patient with an excellent stone clearances.Conflict of interests: NoneConsent: Written informed consent was obtained from the patient for the accompanying images.
Factor Activity Levels and Bleeding Scores in Pediatric Hemophilia Carriers Enrolled...
John Puetz
Brian Hu

John Puetz

and 1 more

May 10, 2023
Background: Multiple studies have now shown that a significant proportion of hemophilia carriers meet criteria for having hemophilia and/or report abnormal bleeding. However, to date, investigations of hemophilia carriers have almost exclusively involved women over 18 years of age. Little is known about factor activity levels and bleeding scores in carriers during childhood. We queried a large deidentified database of subjects with bleeding disorders residing in the United States to determine factor activity levels and bleeding scores. Procedures: The ATHNdataset was queried for hemophilia carriers under 18 years of age. Collected information included demographics, factor activity levels, bleeding scores. Results: Over 700 carriers in the pediatric age group were identified of which 626 submitted factor activity levels. Nearly half had factor activity levels less than 40 IU/dL, thereby meeting criteria for having hemophilia. Of those reporting bleeding scores, only 13.5% reported an abnormal bleeding score for age. The proportion reporting abnormal bleeding scores was higher in those with factor levels less than 40 IU/dL (23%) than those greater than 40 IU/dL (9.7%). Conclusions: The proportion of pediatric carriers with hemophilia was double of that previously reported for adults. Of those with hemophilia reporting a bleeding score, the majority (77%) did not report an abnormal bleeding score for age. However, nearly 10% of pediatric carriers not meeting criteria for having hemophilia reported abnormal bleeding scores for age. Similar results are reported in adults suggesting that factor activity levels may not be predictive of bleeding symptoms in carriers.
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