Background: Reliable HPV testing and genotyping are essential for quality assurance in HPV-based primary screening, disease management and for monitoring the impact of HPV vaccination. The clinical validation of HPV molecular diagnostic assays has significantly contributed to these objectives, however little emphasis has been placed in assuring sample quality. This study aims to assess the accuracy of sample cellularity assessment using C-C Motif Chemokine Receptor 5 (CCR5) gene target as a marker of sample adequacy in molecular diagnostics. Methods: Jurkat cell line samples were counted both using Thoma cell-counting chamber and Fluorescent-Activated Cell Sorting (FACS). Jurkat cell line samples at three different concentrations were subsequently evaluated using the OncoPredict HPV Quality Control (QC) real-time PCR assay, employing CCR5 for molecular cellularity quantification. Results: Cellularity values obtained were comparable across the 3 different methods for all dilutions of the cell line tested. Conclusions: The results obtained from this study show that CCR5 represents a promising molecular marker for the accurate quantification of sample cellularity, confirming its use as a reliable sample adequacy control, thus reducing the risk of “false negative” results.

The current work is dedicated to the search for new high-energy materials (HEMs) with improved characteristics which are gained through agglomeration with salts. The research was performed by Becke’s three-parameter hybrid functional approach with non-local correlation provided by Lee, Yang, and Parr and cc-pVTZ basis set. The geometry, total energy, and heat of formation of the most stable compounds forming due to 3-amino-5-[(2, 4, 6-trinitrophenyl) amino]-1H-1, 2, 4-triazole (APATO) within salts selected were obtained to foresee its influence on resistance to shock stimuli, detonation pressure, and velocity of the materials under study. Results obtained allow us to foresee that only agglomeration with precise salts could lead to significant improvement in the stability of the specific high-energy materials and the resistance to shock stimuli. We also show that the agglomeration leads to better energetic properties of the above compound, although the improvement could be insignificant in some cases.

G-protein-coupled receptors (GPCRs) are ubiquitous sensors and regulators of cellular functions. Each GPCR exists in complex aggregates with multiple resting and active conformations. Designed to detect weak stimuli, GPCRs can also activate spontaneously, resulting in basal ligand-free signaling. Agonists trigger a cascade of events leading to an activate agonist-receptor-G protein complex with high agonist affinity. However, the ensuing signaling process can further remodel the receptor complex to reduce agonist affinity, causing rapid ligand dissociation. The acutely activated ligand-free receptor can continue signaling, as proposed for rhodopsin and  opioid receptors, resulting in robust receptor activation at low agonist occupancy with enhanced agonist potency. Continued receptor stimulation can further modify the receptor complex, regulating sustained ligand-free signaling - proposed to play a role in opioid dependence. Basal, acutely agonist-triggered, and sustained elevated ligand-free signaling could each have distinct functions, reflecting multi-state conformations of GPCRs. This review addresses basal and stimulus-activated ligand-free signaling, its regulation, genetic factors, and pharmacological implications, focusing on opioid and serotonin receptors, and the growth hormone secretagogue receptor (GHSR). Ligand-free signaling of intracellular 5-HT2A receptors could mediate therapeutic effects of psychedelic drugs. Research avenues are suggested to close gaps in our knowledge of ligand-free GPCR signaling.

The clinical and genetic studies strongly support a significant connection between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD) and identify ASCVD as the primary cause of death in NAFLD patients. Understanding the molecular factors and mechanisms regulating these diseases, is critical for developing novel therapies that target them simultaneously. Our preliminary immunoblotting experiments demonstrated elevated expression of nidogen 2 (NID2), a basement membrane glycoprotein, in human atherosclerotic vascular tissues and murine steatotic livers. Therefore, we investigated the role of NID2 in regulating hepatosteatosis and atherosclerosis utilizing Western diet-fed Apoe-/- mice with/without NID2 overexpression. Quantitative real-time PCR confirmed increased NID2 mRNA expression in multiple organs (liver, heart, kidney and adipose) of NID2-overexpressing mice. Male mice with NID2 overexpression exhibited higher liver and epididymal white adipose tissue mass, increased hepatic lipid accumulation and fibrosis. Additionally, these mice developed larger atherosclerotic lesions in the whole aortas and aortic roots, with increased necrotic core formation. Mechanistic studies showed reduced AMPK activation in the livers of NID2-overexpressing mice compared with controls, without any effects on hepatic inflammation. In conclusion, these findings suggest that NID2 plays a deleterious role in both hepatosteatosis and atherosclerosis, making it a potential therapeutic target for these conditions.

A convenient and efficient strategy for the preparation of 2-sulfonylindoles has been achieved through iodophor/H2O2-mediated 2-sulfonylation of indoles with readily available sulfonyl hydrazides in aqueous phase. Iodophor is commercially available and serves as the green catalyst and aqueous phase. A series of 2-sulfonylated products from indoles and N-methylpyrrole were synthesized in moderate yields in only 10 min. Control experiments were also conducted to reveal the mechanism. This method is environment friendly, easy to operate and suitable for a wide range of substrates.

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase (FIASMA) against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

COVID-19 pandemic outbreak challenged the global public health in last couple of years. Throughout the pandemic period, numbers of mutant strains of SARS- CoV-2 created challenges for the infected patients with diverse pathophysiology and immune response. Variant of Concern (VOC) alpha (B.1.1.7), delta (B.1.617.2) and omicron (B.1.1.529) grew most notable for causing the epidemiological manifestations, which eventually caused elevated infectivity resulting in significant mortality. This review indicates the comparative analysis of the immune-pathophysiological mechanisms in respect to the aforementioned strains of SARS-CoV-2.

Accurate fuel mapping plays a crucial role in fire detection and management strategies. This paper presents a method for discriminating between wildfire fuel types by exploiting together remote sensing data and Convolutional Neural Networks (CNN). Specially, a CNN-based classification approach that leverages Sentinel-2 imagery is exploited to accurately classify fuel types into seven preliminary main classes (conifers, broadleaf, shrubs, grass, bare soil, urban areas, and water bodies) with an high accuracy of 0.99$\%$. To further refine the fuel mapping results, subclasses were generated from the seven principals by using biomass and bioclimatic maps. These additional maps provide complementary information about vegetation density and climatic conditions, respectively. By incorporating this information, we align our fuel type classification with the widely used Scott/Burgan fuel classification system. This refinement step allows for a more detailed and comprehensive assessment of fuel types, enhancing the accuracy and effectiveness of fire management efforts, which can be utilized by fire management agencies, policymakers, and researchers for improved fire behavior prediction and mitigation practices. The proposed approach presents a valuable tool for enhancing fire management, contributing to more effective wildfire prevention and mitigation efforts.

A large population has been infected by COVID-19 (Coronavirus disease-19) and it has been necessary a rapid and simple diagnostic method to detect the SARS-CoV-2and control its spread. We developed a colorimetric reverse transcription-loop-mediated isothermal amplification (RT-LAMP) kit that allow the detection of SARS-CoV-2 from nasopharyngeal swab samples without the need of RNA extraction. The kit utilizes three sets of LAMP primers targeting two regions of ORF1ab and one region in the E gene. The results are reported using colorimetric change of hydroxynaphthol blue, enabling visual interpretation without the need for expensive instrument. The kit demonstrated sensitivity to detect between 50 and 100 copies of the viral genome per reaction. The kit was authorized by the National Administration of Drugs, Food and Technology (ANMAT) of Argentina after validation using samples previously analyzed by gold standard RT-qPCR. The results showed sensitivity of 90,6 % and specificity of 100%, consistent with conventional RT-qPCR. In silico analysis confirmed the recognition of SARS-CoV-2 Variants of Concern (VOCs) B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.427, B.1.429and lineages of variant Omicron (B.1.1.529) with 100% homology. This rapid, simple, and sensitive RT-LAMP method paves a way for a large screening strategy to be carried out at locations lacking sophisticated-instrumental and trained-staff, as particularly happen at regional hospitals and medical centers from rural areas.

We provide a summary of various epidemiological parameters related to COVID-19 such as incubation period, serial interval and other parameters. Understanding these parameters is important for developing prevention strategies. SARS-CoV-2 can be transmitted by droplets and close contact, but there is evidence of airborne transmission. Aerosol-generating procedures have been identified as one of the specific risk factors for healthcare workers. Super-spreading events refer to situations where a small number of individuals cause the majority of infections. The basic reproductive number (R0) and the spread parameter (k) are used to characterise the transmissibility of the disease. Estimated values for R0 range from 2 to 3 and the estimated value for k is 0.1.The duration of infectiousness depends on viral load and shedding. Viral load varies according to factors such as clinical spectrum, type of variant and vaccination status. The relationship between viral load and infectivity is not fully understood.With regard to the frequency of symptoms and signs of COVID-19, fever, cough, fatigue and dyspnoea are common. The prevalence of olfactory and gustatory dysfunction (OGD) varies between studies and countries. Age and comorbidities are factors associated with olfactory dysfunction.Estimates of the proportion of asymptomatic patients range from 6% to 96%. Asymptomatic transmission is considered likely and is important for control measures.We reviewed the quantitative semiology of COVID-19 is reported on sensitivity, specificity and likelihood ratios of signs.Finally, we also review risk factors for COVID-19 (including health care workers), co-infections, and epidemiology of variants..

SARS-CoV-2 pandemic caused an increase in Intensive Care Unit (ICU) hospitalizations with rise in morbidity and mortality; nevertheless, there is still little evidence of pandemic impact on antibiotic resistance in ICU. Retrospective monocentric epidemiological study. All microorganisms isolated from all patients admitted to E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. Aim of the study was to describe and analyze the impact of SARS-CoV-2 pandemic on ICU microorganisms resistance patterns. 1,771 microorganisms identified, 221 (12.47%) had resistant pattern (Resistant Organisms; ROs) isolated from 1,679 patients during 12,030 hospitalization days. The majority of ROs were Gram-negative (79.66% 2018, 77.29% 2019, 61.83% 2020, 62.56% 2021, 60.75% 2022), but increase of Gram-positive microorganisms was observed (20.34% to 39.25% between 2018-2022). Prevalence of AR was: 19.44% 2018, 11.54% 2019, 38.04% 2020, 34.15% 2021, 39.29% 2022 for Gram-positives; 19.86%, 13.56%, 18.12%, 12.41%, 12.31% for Gram-negatives. Incidence of Ros showed COVID-related rise in 2020-2021, followed by a lowering trend since 2021, with new rise in 2022. Possible explanations are antibiotic overtreatment and drop of containing measures. Interesting finding is the cumulative lowering trend of carbapenem resistant K. pneumoniae and P. aeruginosa probably due to different patient features.

Introduction SARS-CoV-2 infection normally damages respiratory system but may likewise impair endocrine organs’ function. Thyroid dysfunction and hyperglycemia are common endocrine complications of SARS-CoV-2 infection. Onset of T1D and associated complications including DKA, hospitalization and death, are thought to be increased during the COVID-19 pandemic. The aim of this study is to review the available data about the incidence rate of T1D and accompanying complications since the beginning of the COVID-19 pandemic. Methods: A systematic review was conducted using electronic databases PubMed and Google Scholar. The keywords “T1D, T1DM, Type 1 DM or Type 1 Diabetes”, “Coronavirus, SARS-CoV-2 or COVID-19” were used to search these databases. Titles and abstracts were screened for selection, and then relevant studies were reviewed in full text. Result: we selected 21 manuscripts out of 296 identified studies. Data about the incidence rate of T1D, hospitalization and death are not consistent across countries, but DKA incidence and severity seem to be higher during the COVID-19 pandemic. Conclusion: Our data collection demonstrated that COVID-19 may or may not increase the incidence of type 1 diabetes. Nevertheless, it is associated with higher incidence and severity of DKA in T1D patients. Antivirals are not fully protective against endocrine complications of SARS-CoV-2 infection. Combining medications that reduce SARS-CoV-2 entry into the cells and modulate the immune response to infection is an alternative practical approach to treating COVID-19.

The recent global emergence of the SARS-CoV-2 pandemic has accelerated research in several areas of science whose valuable outputs and findings can help to address future health challenges in the event of emerging infectious agents. We performed a multifocus shotgun analysis to compare differences in bacterial spectrum and viral presence through culture-independent RNA sequencing. We compared the microbiome of healthy people versus those with varying degrees of COVID-19 severity. We observed a significant increase in the diversity of microbial species in patients with COVID-19 regardless of disease severity. Some bacterial phyla, such as Actinobacteria, are significantly more abundant in healthy people than in infected people, whereas Bacteroides are less abundant in the latter. Infected people, regardless of severity and symptoms, have the same proportional representation of Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes, and Fusobacteriales the same. In addition to SARS-CoV-2 and numerous phage groups, we identified sequences of clinically significant viruses such as Human Herpes Virus 1, Human Mastadenovirus D, Molluscum Contagiosum Virus, and Rhinovirus A in several samples. Analyses were performed retrospectively, therefore, in the case of SARS-CoV-2 various WHO variants such as Alpha (B.1.1.7), Delta (B.1.617.2), Omicron (B.1.1.529), and 20C strains are represented. Additionally, the presence of specific virus strains has a certain effect on the distribution of individual microbial taxa.

The Mont-Saint-Michel is known worldwide for its unique combination of the natural site and the Medieval abbey at the top of the rocky islet. But the Mont is also located within an estuarine complex, which is considerably silting up. For two decades, large-scale works were planned to prevent the Mont from being surrounded by the expanding salt meadows. The construction of a new dam over the Couesnon River, the digging of two new channels, and the destruction of the causeway were the main operations carried out between 2007 and 2015. The remote sensing approach is fully suitable for evaluating the real impact of the engineering project in both time and space, particularly the expected large-scale hydrosedimentary effects, for reestablishing the maritime landscape around the Mont. Sentinel-2 satellite data have been used for the period from 2015 to 2023. Aster data were used for the previous period covering 2000 to 2017. Aerial photographs and an ALOS scene have been also used. The remote sensing approach is based on time-series images. It allows identifying local or regional consequences and temporary or permanent effects. The migration of the different channels (especially for the new west and east Couesnon river courses) and the erosion-progradation balance of the vegetation through space and time are the main features to study. Between 2007 and 2023, the erosion of the salt meadows is significant to the south-west of the Mont (− 150 ha) but more limited to the south-east (− 65 ha). The erosion effect is limited to the immediate environment because the vegetation fringe of the uppermost tidal flat along the main dike is slightly increasing (+ 35 ha) to the west and to the east (+ 40 ha). During the same period, the sedimentation considerably increased to the north-east of the Bay, between the Bec d’Andaine, the Grouin du Sud and Tombelaine islet, which seems now facing the same silting-up problem. At this stage, the remote-sensing survey indicates mixed results for the engineering project.

Among cross-sectional imaging modalities, computed tomography (CT) is more available and faster; however, magnetic resonance (MR) performs better in terms of sensitivity and specificity, due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR depends mainly on the primary tumour histology: in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights on the tumour origin. The time-point of tumour evolution, previous or ongoing treatments and the peritoneal spaces where they occur, also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is mandatory in detection and characterization of peritoneal deposits. Several benign and malignant conditions may show similar imaging features that overlap those of PC, making the differential diagnosis challenging. Clinical history, laboratory findings and previous imaging examinations must be considered to achieve the correct diagnosis.

The COVID-19 pandemic has had a major impact on health systems around the globe and Romania is no exception. The impact on healthcare expense for pregnant women has been considerable, especially in COVID-only tertiary centers, where specialized care is being provided .The aim of this study is to analyze the impact of SARS-CoV-2 infection on healthcare costs, in particular by managing cases in COVID-only maternity. Material and Methods: The objective of the study was to analyze if the model adopted by the health system consisting in complete separation of delivering obstetrical care for covid and non-covid patients was efficient. We conducted an observational study in which we compared a group of pregnant women infected with SARS-CoV-2 (study group) with a control group in which we included uninfected pregnant women. The patients were recruited from Bucur Maternity Hospital, declared a COVID-only center in march 2020. We compared the two groups in terms of expenses over the entire period of hospitalization, i.e. expense on hospitalization, medicines, medical supplies, and medical investigations.

The COVID-19 pandemic has been challenging for society, especially for those residing in long-term care facilities (LTCF). This study aimed to describe rates of infection, hospitalization, and death due to COVID-19 among older people and staff of LTCF in a state of Southeastern Brazil and identify strategies to prevent and control the disease spread. This cross-sectional study was conducted with 164 LTCF (6,017 older people). Among the studied LTCF, 48.7% confirmed COVID-19 infection in older people, resulting in 39.6% hospitalization and 32.3% death among infected. Moreover, 68.9% of LTCF confirmed COVID-19 infection in the staff, with 7.3% hospitalization and 1.2% death. Preventive measures were identified and classified as organizational, infrastructure, hygiene items and personal protective equipment, and staff training against COVID-19. These measures showed strategies and barriers experienced in the daily routine of LTCF during the pandemic. LTCF in Brazil experienced challenges similar to observed worldwide.

Patients with COVID-19 demonstrate higher rates of cardiovascular complications, including thromboses and thromboembolism. One may suppose that the action of SARS-CoV-2 transforms stable atherosclerotic plaques into unstable status. Cardiovascular complications in COVID-19 may be caused by progressive viral alteration the blood vessels, including vasa vasorum. A lethal case of ischemic brain disease caused by cerebral atherosclerosis and exacerbated with a stroke during COVID-19 infection is briefly described. The results of autopsy showed perivascular lymphocytic infiltration and signs of vasa vasorum vasculitis with thrombi of adventitial microvasculature. The data discussed in the article are interpreted in context of the concept giving the important role in atherogenesis to vasa vasorum.

Background: Repeated SARS-CoV-2 infections are plausible and related published data are scarce. We aimed to identify factors associated with the risk of recurrent (three episodes) laboratory-confirmed symptomatic SARS-CoV-2 infections. Methods: A retrospective cohort study was conducted and 1,700 healthcare workers were enrolled. We used risk ratios (RR) and 95% confidence intervals (CI) to evaluate factors associated with symptomatic SARS-CoV-2 infections. Results: We identified 14 participants with recurrent illness episodes. Therefore, the incidence rate was 8.5 per 10,000 person-months. In multiple model, vaccinated adults (vs. unvaccinated, RR = 1.05 [1.03 - 1.06]) and those with a severe first illness episode (vs mild disease, RR = 1.05 [1.01 - 1.10]) were at increased risk for repeated symptomatic SARS-CoV-2 reinfections. Increasing age showed a protective effect (per each additional year of age: RR = 0.98 [0.97 - 0.99]). Conclusions: Our results suggest that recurrent SARS-CoV-2 infections are rare events in adults and they seem to be determined, partially, by vaccination status and age.

The COVID-19 pandemic has highlighted the importance and urgent need of rapid and accurate diagnostic tests for detection and screening of this infection. In our proposal, a biosensor based on the ELISA immunoassay was developed for monitoring antibodies against SARS-CoV-2 in human serum samples. The SARS-CoV-2 nucleocapsid protein (N-protein) was selected as a specific receptor for the detection of SARS-CoV-2 nucleocapsid immunoglobulin G. Thus, the N-protein was immobilized on surface of screen-printed carbon electrode (SPCE) modified with carboxylated graphene (CG). The IgG-SARS-CoV-2 nucleocapsid concentration was quantified using a secondary antibody labelled with horseradish peroxidase (HRP) (anti-IgG-HRP) catalyzed by 3,3’,5,5’-tetramethylbenzidine (TMB) mediator by chronoamperometry. A linear response was obtained in the range of 1:1000-1:200 v/v in phosphate buffer solution (PBS) and the limit of detection calculated was of 1:4947 v/v. The chronoamperometric method showed electrical signals directly proportional to antibody concentrations due to Ag-Ab specific and stable binding reaction.

Viral variant analysis is a bedrock of the disease surveillance. When combined with temporospatial analysis variant analysis can further the knowledge of disease spread in a study area. This paper suggests a method to perform the analysis in an operational setting which will allow for real-time surveillance of viral variants and allow local public health professionals to rapidly respond to changes in the evolution of the disease. This method includes three main subprocesses: preprocessing, analysis, and rendering. This method can be performed across multiple software platforms. A use case is given in which it was found that this method helped a hospital system understand the spread of SARS-CoV-2 in Northeast, Ohio.

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), etiological agent of the novel coronavirus disease 2019 (COVID-19), has spread since December 2019, resulting in massive health and economic crisis worldwide. While efforts to stop the pandemic are crucial, collecting epidemiological data to help manage current and future pandemics will be important. In addition to humans, serological and molecular based studies have demonstrated SARS CoV-2 exposure in several wild, domestic and farmed animals. For examples Shriner and the team showed serologically an exposure of 40% to the white deer living in close proximity to urban centers. Additional reports have also emerged of susceptibility of animal’s species like cats, ferrets, raccoon dogs, cynomolgus macaques, rhesus macaques, white-tailed deer, rabbits, Egyptian fruit bats, and Syrian hamsters to SARS-CoV-2 infection.. It’s worth emphasizing that these reports are based on experimental data mostly derived from Europe, USA, South America and parts of Asia. In limited instances natural infections of SARS-CoV-2 have been reported in pet dogs, cats, tigers, lions, snow leopards, pumas, gorillas at zoos and farmed mink and ferrets. The presence of the virus in animal species and an understanding of whether these are natural or recent human to animal transmissions is important. It’s possible that such transmission could passage the virus or subject the virus to a different immunological pressure thereby helping with the development of viral variants in addition to being a host for future reservoirs of the virus. In Kenya SARS-CoV-2 was first detected on March 12th 2020 from imported human cases of persons who had travelled from the United States. This was followed by detection of imported cases majorly from China, Sweden and United Kingdom. Later infections were confirmed in Nairobi and Mombasa suggesting further cases of disease importations through the major ports of entry. However, no comparable data on animal exposure have hitherto been generated in Kenya. To address this key concern, we focused on three objectives; 1) development of a robust antibody ELISA based on crude SARS-CoV-2 lysate. 2) SARS-CoV-2 serology of domestic animals in Kenya. 3) Corroboration of the crude lysate based seroprevalence data and a commercial ELISA kit based on the Spike receptor binding domain (RBD) antigen. Our sample set included camel sera (both pre- & post outbreak sera), as well as sera from cats and dogs collected at the peak of the pandemic. Our results using the ELISA based on crude SARS-CoV-2 lysate indicated SARS-CoV-2 antibodies in camels (71%, N=145), cats 11% (N=16) and dogs (81%, N=36) with varying titer levels. These findings were comparable to those obtained using the commercial ELISA kit based on the spike RBD antigens. In summary, the data warrants two key conclusions: (i) we have demonstrated that the crude lysate ELISA allows for SARS-CoV-2 antibody detection, and given its potential to offer robust detection could be applied for initial mass screening (ii) although the current study cannot disentangle the relative contributions of antigenic cross-reactivity, pre-pandemic exposure to SARS-CoV-2 or human-animal transmission, it nonetheless demonstrates for the first time the prevalence of SARS-CoV-2 like antibodies in domestic and wild animals in Kenya. Our findings set the scene for further research into the prevalence of SARS-CoV-2 in domestic and wild animals to understand their potential epidemiological implications.

Background: The isoflurane minimum alveolar concentration (MAC) was measured in rats chronically treated with WIN 55,212-2. Methods: The isoflurane MAC was determined in 24 male rats from the end expiratory samples at time of tail clamping under the following conditions: without treatment (MACISO), in rats treated for 21 days with WIN 55,212-2 (MACISO+WIN55) and other group 8 days after stopping treatment for 21 days with WIN 55,212-2 (MACISO+WIN55+8D). Results: The MACISO was 1.32 ± 0.06. In the MACISO+WIN55 group the MAC increase to 1.69 ± 0.09 (28%). After 8 days stopping treatment, MAC did not decrease significantly 1.67 ± 0.07 (26%). Conclusions: The administration for 21 days of WIN 55,212-2 increases the MAC of isoflurane in rats; this effect does not disappear after 8 days of discontinuing treatment with the synthetic cannabinoid.

Background The World Health Organization has recently recognized Long COVID, calling the international medical community to strengthen research and comprehensive care of patients with this condition. However, if Long COVID pertains to children as well is not yet clear. Methods An anonymous, online survey was developed by an organization of parents of children suffering from persisting symptoms since initial infection. Parents were asked to report signs and symptoms, physical activity and mental health issues. Only children with symptoms persisting for more than four weeks were included. Results 510 children were included (56.3% females) infected between January 2020 and January 2021. At their initial COVID-19 infection, 22 (4.3%) children were hospitalized. Overall, children had persisting COVID-19 for a mean of 8.2 months (SD 3.9). Most frequent symptoms were: Tiredness and weakness (444 patients, 87.1% of sample), Fatigue (410, 80.4%), Headache (401, 78.6%), Abdominal pain (387, 75.9%), Muscle and joint pain (309, 60.6%), Post-exertional malaise (274, 53.7%), rash (267, 52.4%). 484 (94.9%) children had had at least four symptoms. 129 (25.3%) children have suffered constant COVID-19 infection symptoms, 252 (49.4%) have had periods of apparent recovery and then symptoms returning, and 97 (19.0%) had a prolonged period of wellness followed by symptoms. Only 51 (10.0%) children have returned to previous levels of physical activity. Parents reported a significant prevalence of Neuropsychiatric symptoms. Conclusions Our study provides further evidence on Long COVID in children. Symptoms like fatigue, headache, muscle and joint pain, rashes and heart palpitations, and mental health issues like lack of concentration and short memory problems, were particularly frequent and confirm previous observations, suggesting that they may characterize this condition. A better comprehension of Long COVID is urgently needed..

Prevention practices have been extensively used to contain the spread of the SARS-CoV-2 virus. These include social distancing, wearing masks, disinfection of hands, and sanitization of contact surfaces. However, the excessive usage of chemical disinfectants pose long term adverse effects to human health and the environment. Development of effective and environmentally friendly biocides, or virucidal agents, will help mitigate the ill effects of chemical disinfectants. Enzymes are potential candidates for the preparation of biocides against bacteria and viruses. Exploration of the virucidal activity of commercial enzymes, will highlight prospective, readily available sources for research on enzyme based biocides. In this study, the virucidal effect of some com-mercial enzyme preparations has been investigated against the SARS-CoV-2 virus. Vida Defense (2000 µg/ml), Excellacor (1500 µg/ml), and SEBkinase (3000 µg/ml) reduced SARS-CoV-2 viral ti-ters by ≥1 log CCID50 (≥90%). ImmunoSEB (6000µg/ml) and Peptizyme SP (500µg/ml) reduced the SARS-CoV-2 viral titers by 0.8 log CCID50 (84.2%). The study indicates that enzyme prepara-tions offer the potential to be explored further for an anti-viral biocide against SARS‐CoV‐2 for reducing the risk of COVID‐19 transmission. However, further studies are mandated to improve efficacy and establish safety.

Background: Coronavirus disease (COVID-19) has caused more than 745,000 deaths worldwide. Vitamin D has been identified as a potential strategy to prevent or treat this disease. The purpose of the study was to measure vitamin D at hospital admission of COVID-19; Methods: We included critically ill patients with the polymerase chain reaction positive test for COVID-19, from March to April, 2020. Statistical significance was defined as P < .05. All tests were 2-tailed; Results: A total of 35 patients (median age, 60 years; 26 [74.3%] male) were included. Vitamin D levels were categorized as deficient for 14 participants (40%). Vitamin D deficiency was associated with vitamin A (P= 0.003) and Zinc (P= 0.019) deficiency and lower levels of albumin (P= 0.026) and prealbumin (P= 0.009). Overall, none of the studied variables were associated with vitamin D status: mortality, intensive care unit (ICU) or hospital stay, necessity of vasoactive agents, intubation, prone position, C reactive protein (CRP), Dimer-D, Interleukin 6 levels (IL-6), ferritin levels, or bacterial superinfection; Conclusions: In this single-center, retrospective cohort study, deficient vitamin D status was found in 40% in COVID-19 critically ill patients. However, deficient vitamin D status was not associated with inflammation or outcome.

The Coronavirus disease 2019 (COVID-19) pandemic is clearly taking a firmer grip on South Africa and more podiatrists will face the potential transmission of SARS-CoV-2. Government response was swift with the implementation of a travel ban, strict national lockdown as well as social distancing and hygiene protocols in line with international health regulations. Co-morbidities such as tuberculosis and HIV/AIDS, endemic to South Africa, are considered a dangerous combination with COVID-19, making many South Africans vulnerable to contracting the COVID-19. Patients with diabetes as well as the aged are vulnerable, both in terms of potential combined complications and challenges in continuity in foot care. The demands of the pandemic may outstrip the ability of the health systems to cope. Should this time arrive, all healthcare practitioners, including podiatrists, would have to step in and take on a role beyond their scope of practice in order to ensure that the healthcare system does not get overwhelmed. It is important for podiatrists to keep abreast with the developments around the COVID-19, in order that they may institute appropriate clinical practice which will ensure maximum protection for themselves, staff and patients as well as providing quality foot health care.

In regions lacking genomic data, analysis of sequences from the early stages of an outbreak can provide important insights into the diversity of pathogens present. Following the detection of the first imported case of COVID-19 in the Northern sector of Ghana on 13^th March 2020, we have now molecularly characterized and phylogenetically analysed sequences including three (3) complete genomes of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) isolated from nine (9) patients observed in Ghana. Eight (8) of these patients reported with a recent history of foreign travel and one (1) with no history of foreign travel. We performed high throughput sequencing for 9 samples following the determination of high concentration of viral RNA. In addition, we estimated the potential impact that long distance transportation of samples to testing centres may have on sequencing outcomes. Here, two samples that were closest in terms of viral RNA concentration but transported from sites which are over 400km apart were assessed. All sequences were compared to previous sequences from Ghana and representative sequences from regions where our patients had previously travelled. Complete genomes were obtained for three (3) sequences and with another near complete genome with a coverage of 95.6%. Sequences with coverage in excess of 80% were found to belong to three lineages namely A, B.1 and B.2. Our sequences clustered in two different clades with the majority falling within a clade composed of sequences from sub-Saharan Africa. Less RNA fragmentation was seen in sample KATH23 which was collected 9km compared with sample TTH6 which was collected and transported over a distance of 400km to the testing site. The clustering of several sequences from sub-Saharan Africa suggests regional circulation of the viruses in the subregion. Importantly, there may be the need to decentralize testing sites and build more capacity across Africa to boost the sequencing output of the subregion.

COVID-19 pandemic has caused a large-scale havoc in almost every country across the globe, putting major challenges for the healthcare system in many parts of the world. Several of the laboratories are running in the race with undying efforts for developing potential vaccine, drugs or therapeutics to treat or prevent the infection. However, with the limited time window and high rate of infection, the task is very big for humanity to find a cure. With hundreds of genomic data of SARS-CoV-2 virus isolates from humans are being submitted almost every day, it is coming into knowledge that virus is mutating, slower in countries with sporadic cases, but higher in countries experiencing large outbreak. These types of mutations in virus may bring challenges in vaccine or therapeutic development for use in each and every country, as each hotspot region may have their own pattern of mutations in virus with ongoing outbreak. In our current study, we retrieved non-synonymous mutation data of around 12,225 SARS-CoV-2 virus samples isolated from humans globally, and discovered all mutations that are collectively happening in antibody epitope regions of the virus country-wise. We found a few numbers of epitope regions in SARS-CoV-2 that are highly conserved collectively in all variants and may be used for epitope-based vaccine development for whole world. We also found epitope regions that are conserved collectively in SARS-CoV-2 variants country-wise and can be used for customized epitope-based vaccine development in each different country.

“Severe acute respiratory syndrome” (SARS) due to Coronavirus (SARS-CoV) infection is a known cause of death. Sometimes demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flue-like symptoms. In this dobtfull cases the forensic pathologist could be requested to define cause of death occurred outside hospital. In this report the authors describe two thorough autopsied cases of SARS-CoV-2 related deaths occurred suddenly at home and not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.

The regulation of apoptosis depends upon the Bcl-2 protein family. The process of cell death and survival is highly complicated and regulated by various types of extrinsic as well as intrinsic network of biological system. Several enzymes and regulators play crucial role in cell death and survival cycle not only in healthy but also in pathological state particularly in cancer. In cancerous cells, various proto-oncogenes and anti-apoptotic proteins are activated and responsible for the cell survival and longevity. The mechanism of activation and inactivation of various proteins in cell survival is regulated by the process of phosphorylation (kinases) and dephosphorylation (phosphatases). The current review will summarize the dynamics of Bcl-2 phosphorylation and its role in apoptosis and cell survival.

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2 or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce an increase in a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines including interleukins IL-1, IL-6, CCL2 protein and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: Low-dose oral interferon-alpha, microdose DNA, low-dose thimerosal and phytocannabinoids.

The emergence of SARS-CoV-2 is a challenge in the actual medical scenario. Besides the classical lung and respiratory disease, patients infected with the virus can present with cardiac injury, and pathogenic mechanisms point to a direct infection of the heart.

OBJECTIVE: Recent worldwide outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of respiratory coronavirus disease 2019 (COVID-19), is a current, ongoing life-threatening crisis and international public health emergency. The early diagnosis and management of the disease remains a major challenge. In this review, we aim to summarize the updated epidemiology, causes, clinical manifestation and diagnosis, as well as prevention and control of the novel coronavirus SARS-CoV-2.MATERIALS AND METHODS: A broad search of the literature was performed in “PubMed” “Medline” “Web of knowledge”, and “Google Scholar” World Health Organization-WHO” using the keywords “severe acute respiratory syndrome coronavirus”, “2019-nCoV”, “COVID-19, “SARS”, “SARS-CoV-2” “Epidemiology” “Transmission” “Pathogenesis” “Clinical Characteristics”. We reviewed and documented the information obtained from literature on epidemiology, pathogenesis and clinical appearances of SARS-CoV-2 infection.RESULTS: The global cases of COVID-19 as of April 2, 2020 have risen to more than 900,000 and morbidity has reached more than 47,000. The incidence rate for COVID-19 has been predicted to be higher than the previous outbreaks of other coronavirus family members, including those of SARS-CoV and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The main clinical presentation of SARS-CoV-2 infection ranges from asymptomatic stages to severe lower respiratory infection in the form of pneumonia. Most of the patients also presented with fever, cough, sore throat, headache, fatigue, myalgia and breathlessness.Individuals at higher risk for severe illness include elderly people and patients with a weakened immune system or that are suffering from a underlying chronic medical condition like hypertension, diabetes, cancer, respiratory illness or cardiovascular diseases.CONCLUSIONS: SARS-Cov-2 has emerged as a worldwide threat, currently affecting 170 countries and territories across the globe. There is still much to be understood regarding SARS-CoV-2 about its virology, epidemiology and clinical management strategies; this knowledge will be essential to both manage the current pandemic and to conceive comprehensive measures to prevent such outbreaks in the future.

Covid-19 has now become a public health concern worldwide. The infection primarily involves the respiratory tract. Hitherto, some Covid-19 pneumonia patients carry the viral nucleic acids, and the active virus was detected in stool specimens. The virus discharged with feces is a potential contagious source. In the present study, three Covid-19 respiratory tract infection patients showed no gastrointestinal symptoms, and two were positive for viral nucleic acids in anal swab specimens remained positive 6 and at least 14 days after virus turned negative in the respiratory tract, respectively (details of the patients were listed in Fig 1). Thus, for Covid-19-infected patients with or without gastrointestinal symptoms, viral nucleic acids in stool specimens or anal swab specimens should be focused on for testing in order to decide the isolation duration of the patient.

Rice is an essential crop for national food security in Egypt. Increasing the population calls for regular increases in rice production. At the same time, cultivated rice crop areas should be decreased because of the gradual scarcity of irrigation water. This means more rice production should be gained from less rice area. This situation calls for the annual accurate system for rice monitoring and yield estimation. Therefore, it is necessary to apply a remotely sensed based system for rice cultivation assessment using satellite imagery parallel with field measurements of some biophysical parameters. Multi-temporal normalized difference vegetation index (NDVI) extracted from twelve sentinel-2 imagery cover the whole summer season with variance and maximum value assessed by ground control points (GCPs), were used to isolate uncultivated areas, then to isolate rice areas and other vegetation covers. object-based classification methods with kappa co-efficient 0.9261 and overall accuracy 94.92% was generated to discriminate rice crop area and other summer crops on the study area. Leaf area index (LAI) for the experiment the l site was calculated using the surface energy balance algorithm for Land (SEBAL) model and then tested versus measured (LAI). NDVI and LAI were used to generate an empirical ran rice yield prediction model. Then, this model was used to produce rice to yield a map. The study was carried out in an experimental site in Kafr Elsheikh governorate with a total area of 5040 Hectare. Produced cultivated land use map showed 95% overall accuracy. High similarity was observed between measured and calculated (LAI) with high accuracy of R2 = 0.94. of Rice, yield map showed expected to yield more to than a month before harvest. The generated yield map was tested using a correlation coefficient between actual yield and estimated yield with high accuracy R2 = 0.9. This method is applicable to estimate the acreage and productivity of rice in the northern Nile delta in adequate time before harvest.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

Introduction: Type 2 diabetes (T2D) is a major driver of health care costs, thus treatments enabling T2D reversal may reduce expenditures. We examined the impact of a T2D continuous care intervention (CCI) on health care utilization. Previous research documented that CCI, including individualized nutrition supported by remote care, simultaneously reduced hemoglobin A1c and medication use and improved cardiovascular status after two years; however, the impact on utilization is unknown. Methods: This study used four years of data (two years pre-intervention, two years post-intervention) from the Indiana Network for Patient Care (INPC) health record. Two methods estimated the impact of CCI on utilization. First, an interrupted time series (ITS) including only CCI participants (n=193) compared post-intervention utilization to expected utilization had the pre-intervention trend persisted. Deviation from the trend was estimated non-parametrically for each 6-month interval after the implementation of CCI . Second, a 1:3 matched comparator group (n=579) was constructed and used for a difference-in-differences (DiD) analysis. The primary outcome was annualized outpatient encounters. Secondary outcomes included emergency encounters and hospitalizations. Results: In two years prior to intervention, CCI participants had a mean of 5.77 annualized encounters (5.62 outpatient, 0.04 hospitalizations, 0.11 emergency). The CCI group showed a reduction in outpatient utilization after intervention. In ITS analysis, 1.6 to 1.9 fewer annualized outpatient encounters occurred in each 6-month interval post-intervention relative to expected utilization based on pre-intervention trends (p<0.01 each 6-month period; 28-33% reduction). The DiD analysis suggested a larger reduction; 5 fewer annualized outpatient encounters in the quarter after intervention, diminishing to 2.5 fewer after 2 years (p<0.01 each quarter). The study was underpowered to draw conclusions about hospitalization and emergency encounters due to the limited number of CCI patients and the rarity of encounters. Conclusions: Outpatient encounters were significantly reduced for a T2D patient population up to 2 years after receiving an individualized intervention supporting nutrition and behavior change through remote care.

T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Background: We previously reported that human keratinocytes express protease-activated receptor (PAR)-2 and play an important role in activated protein C (APC)-induced cutaneous wound healing. This study investigated the involvement of PAR-2 in the production of gelatinolytic matrix metalloproteinases (MMP)-2 and -9 by APC during cutaneous wound healing. Methods: Full-thickness excisional wounds were made on the dorsum of male C57BL/6 mice. Wounds were treated with APC on days 1, 2, and 3 post-wounding. Cultured neonatal foreskin keratinocytes were treated with APC with or without intact PAR-2 signalling to examine the effects on MMP-2 and MMP-9 production. Murine dermal fibroblasts from PAR2 knock-out (KO) mice were also assessed. MMP-2 and -9 were measured by gelatin zymography, fluorometric assay, and immunohistochemistry. Results: APC accelerated wound healing in WT mice, but had negligible effect in PAR-2 KO mice. APC stimulated murine cutaneous wound healing was associated with differential 0temporal production of MMP-2 and MMP-9, with the latter peaking on Day 1 and the former on Day 6. In-hibition of PAR-2 in human keratinocytes reduced APC-induced MMP-2 activity 25~50, but had little effect on MMP-9. Similarly, APC-induced MMP-2 activation was reduced by 40% in cultured dermal fibroblasts derived from PAR-2 KO mice. Conclusion: This study shows for the first time that PAR-2 is essential for APC-induced MMP-2 production. Considering the important role of MMP-2 in wound healing, this work helps explain the underlying mechanisms of action of APC to promote wound healing through PAR2.

Patients with COVID-19 have coagulation and platelet disorders, with platelet’s alterations and thrombocytopenia representing negative prognostic parameters, being associated with severe forms of the disease, and increase lethality. Methods: Aim of this study was to study expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation Results: a total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19 +), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS CoV-2 (-) negative lungs (COVID-19 -), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1 positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of dead patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocytes over-expression in the lung. Conclusions: microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

Plazomicin is a recently U.S. Food and Drug Administration (FDA)-approved semisynthetic aminoglycoside. Its structure consists of a sisomicin scaffold modified by adding a 2(S)-hydroxy aminobutyryl group at the N1 position and a hydroxyethyl substituent at the 6′ position. These substitutions produced a molecule refractory to most aminoglycoside-modifying enzymes. The main enzyme within this group that recognizes plazomicin as substrate is the aminoglycoside 2′-N-acetyltransferase type Ia [AAC(2′)-Ia], which reduces the antibiotic’s potency. Designing formulations that combine an antimicrobial with an inhibitor of resistance is a recognized strategy to extend the useful life of existing antibiotics. We have recently found that several metal ions inhibit acetylation of numerous aminoglycosides catalyzed by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib]. In particular, Ag1+, which also enhances the effect of aminoglycosides by other mechanisms, is very effective in interfering with AAC(6′)-Ib-mediated resistance to amikacin. Here we report that silver acetate is a potent inhibitor of AAC(2′)-Ia-mediated acetylation of plazomicin in vitro, and it reduces resistance levels of Escherichia coli carrying aac(2′)-Ia. The resistance reversion assays produced equivalent results when the structural gene was expressed under the control of the natural or the blaTEM-1 promoters. The antibiotic effect of plazomicin in combination with silver was bactericidal, and the mix did not show significant toxicity to human embryonic kidney 293 (HEK293) cells.

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)–cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch inducing expression of various antioxidative enzymes such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR–CYP1A1 signaling and activates the NRF2–antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR–CYP1A1 inhibition and NRF2 activation may be useful in managing dioxin-related health hazards.

We report here the synthesis and characterization of new N-(3-(8-bromoimidazo[1, 2-a]pyridin-2-yl)-4-fluorophenyl)benzamide derivatives. This collection was obtained from 3-(8-bromoimidazo [1,2-a]pyridin-2-yl)-4-fluoroaniline(5). The family of new compounds was characterized by ¹H-NMR, ¹³C-NMR, FT-IR and LC-MS analysis.

Anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids, homocysteine (Hcy)-thiolactone, and proteins modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of mechanisms by which low PON1 leads to disease and high PON1 is protective. Studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that disruption of these processes leads to disease.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

This is an expanded and revised version of the article: A. Tyszka, Statements and open problems on decidable sets X⊆N, Pi Mu Epsilon J. 15 (2023), no. 8, 493-504. The main results were presented at the 25th Conference Applications of Logic in Philosophy and the Foundations of Mathematics, see http://applications-of-logic.uni.wroc.pl/XXV-Konferencja-Zastosowania-Logiki-w-Filozofii-i-Podstawach-Matematyki. We assume that the current mathematical knowledge is a finite set of statements which is time-dependent. Nicolas D. Goodman observed that epistemic notions increase the understanding of mathematics without changing its content. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth from a particular context. Edmund Landau's conjecture states that the set P(n^2+1) of primes of the form n^2+1 is infinite. Landau's conjecture implies the following unproven statement Φ: card(P(n^2+1))<ω ⇒ P(n^2+1)⊆[2,(((24!)!)!)!]. We heuristically justify the statement Φ. This justification does not yield the finiteness/infiniteness of P(n^2+1). We present a new heuristic argument for the infiniteness of P(n^2+1), which is not based on the statement Φ.

CO2-soluble surfactant foam systems have garnered significant attention in the fields of enhanced oil and gas recovery, environmental protection, and greenhouse gas emission reduction. This review provides a comprehensive explanation of the basic theory of CO2-soluble surfactant foam, the mechanism of enhanced oil recovery, and the classification and application of various CO2-soluble surfactants.The mechanism of enhanced oil recovery by CO2-soluble surfactant foam involves the effective reduction of CO2 fluidity, the decrease in oil-air flow ratio, and the stabilization of the displacement front. Foam plays a vital role in mitigating the issues of channeling and gravity separation often caused by simple CO2 injection. The reduction in gas fluidity can be attributed to the increase in apparent viscosity and trapped gas fraction.Future research should prioritize the development of more efficient and environmentally-friendly CO2-soluble surfactants. It is essential to further explore the advantages and challenges associated with their practical applications in order to maximize their potential impact.

Addressing escalating energy demands and greenhouse gas emissions in the oil and gas industry has driven extensive efforts in carbon capture and utilization (CCU), focusing on power plants and industrial facilities. Utilizing CO2 as a primary feedstock for industrial fuels and petrochemical materials offers a favorable alternative to sequestration, with byproducts substituting traditional chemical feedstocks. This comprehensive review explores the current landscape of CO2 capture technologies, examining opportunities, economic viability, and efficiency challenges. It provides a detailed analysis of various CO2 utilization methods and the combined process of capture and utilization. The review highlights primary obstacles in planning, production, and widespread implementation, emphasizing the need for strategic integration of materials research, process performance, and cost-effectiveness to advance new technologies.

Long Covid or post-acute sequelae of SARS-CoV-2 infection (PASC) can manifest as long-term symptoms in multiple organ systems, including respiratory, cardiovascular, neurological, and metabolic systems. In patients with severe COVID-19, immune dysregulation is significant, and the relationship between metabolic regulation and immune response is of great interest in determining the pathophysiological mechanisms. We aimed to characterize the metabolomic footprint for recovering severe COVID-19 patients in three consecutive time points and compare metabolite levels to controls. Our findings add proof of dysregulated amino acid metabolism in the acute phase, and dyslipidemia, glycoprotein level alterations, and energy metabolism disturbances in severe COVID-19 patients 3-4 months post hospitalization.

The primary objective of this study is to synthesize, elucidate the structural properties, and ex-plore the biological activity of novel metal complexes derived from 6-methyl-2-thiouracil and 6-propyl-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activ-ity of newly formed Cu(II) and Pd(II) complexes with two substituted 2-thiouracil ligands. The structural attributes of these newly developed compounds are thoroughly discussed based on data derived from melting point analysis, MP-AES for Cu and Pd, UV-Vis, IR, ATR, 1H NMR, 13C NMR and Raman spectroscopy. The interpretation of the complex spectra is assisted by the data for 6-methyl-2-thiouracil and 6-propyl-2-thiouracil obtained from 1H-1H COSY, DEPT-135, HMBC and HMQC spectra. In addition, the antimicrobial activity of these complexes and the free ligands are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts.

Coronavirus disease 2019 (COVID-19), an infectious disease pandemic, affected millions of people globally, resulting in high morbidity and mortality. Causing further concern, significant proportions of COVID-19 survivors suffer from the lingering health effects of severe acute respiratory syndrome virus 2 (SARS-CoV-2), the pathogen that causes COVID-19. One of the diseases manifesting as a post-acute sequela of COVID-19 is new-onset diabetes. This systematic review and meta-analysis will perform a comprehensive and systematic literature search to estimate the burden of new-onset diabetes after COVID-19. Specifically, this study will estimate the magnitude of the incidence, risk, and population-attributable fraction of new-onset diabetes. The study will also explore and summarize the data on the natural history or clinical course of the new-onset diabetes cases. Five bibliographic databases, including PubMed, MEDLINE, Embase, Scopus, and Web of Science, will be searched for eligible studies. The World Health Organization COVID-19 Research Database, preprint servers, and conference abstracts will also be searched. Cohort studies of COVID-19 patients of all ages providing data on new cases of diabetes in the post-acute phase of the illness will be included. The comparators to estimate the pooled risk ratio will be those with no diagnosis of COVID-19 or those infected with other respiratory tract infections. The findings of this study will likely inform clinical practice, public health guidelines, and policies for early detection and treatment of new-onset diabetes cases in the long-COVID phase. This protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: No.CRD42020200432).

In this work, optimal consumption and investment strategies are derived for risk-averse investors under the 4/2 stochastic volatility class of models. We work under an expected utility (EUT) framework and consider a Constant Relative Risk Aversion (CRRA) investor, who might also be ambiguity-averse. The corresponding Hamilton-Jacobi-Bellman (HJB) and HJB-Isaacs (HJBI) equations are solved in closed-form for a subset of the parametric space and under some restrictions on the portfolio setting, for complete markets. Conditions for proper changes of measure and well defined solutions are provided. These are the first analytical solutions for the 4/2 stochastic volatility model and the embedded 3/2 model for the type of excess returns established in .

The aim of this study was to analyze other possible new markers of severity that can be assessed in patients with type 2 diabetes and SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus and infected with the SARS-CoV-2 virus, and 45 healthy persons as control. The serum level of ceruloplasmin at hospital admission was statistically significant directly correlated with the severity of COVID-19 (Coronavirus disease) (p=0.037) and with the serum level of IL-6 (Interleukine 6) (p=0.000). Ceruloplasmin was statistically significant inversely correlated with serum iron level (p=0.000). However, we observed that ACE (Angiotensin converting enzyme) decreased in severe forms of the infection with SARS-CoV-2 virus in patients with type 2 diabetes (p=0.001). Moreover, the decrease in ACE level was correlated with an increase in IL-6 level in these patients (p=0.001). IL-6 increase was statistically significant inversely correlated with serum iron, transferrin and ACE levels. There was a noticed a decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p=0.000). In addition to the known severity factors in the context of infection with the new coronavirus, decreased concentrations of ceruloplasmin, ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters analyzed at the hospital admission could show the evolution towards the severe forms of infection with the SARS-CoV-2 virus.

The pandemic associated with SARS-CoV-2 is a worldwide public health challenge. The WHO has proposed to achieve 70% COVID-19 vaccination coverage in all countries by mid-2022. Nevertheless, the prevention strategy based on COVID-19 vaccination and other applied prevention measures have not been sufficient to prevent SARS-CoV-2 epidemic waves. The study assessed the vaccination coverage that would be required to establish herd immunity against SARS-CoV-2 by taking into account virus transmissibility (Ro values from 1.1 to 10) and Covid-19 vaccination effectiveness. The study found that Covid-19 vaccination programs could establish herd immunity against SARS-CoV-2 with Ro &lt; 3 with levels of Covid-19 vaccination effectiveness of 10−100% and against viruses with Ro values ranging from 3 to 10 with levels of Covid-19 vaccination effectiveness of 70−100%. Factors reducing Covid-19 vaccination effectiveness (emergent variants, reinfections, high risk individuals) and factors increasing SARS-CoV-2 transmissibility (close settings) increased percentages of vaccination coverage that would be required to establish herd immunity. The vaccination coverage objective of 70% could be adequate against SARS-CoV-2 with Ro values of 1.1−2.5, while percentages of vaccination coverage of 80% and 90% could be more adequate against viruses with Ro values of 2.5−3.5 and &gt;3.5, respectively. On February 2022, the vaccination coverage for complete vaccination was lower than 70% in 73.2% of the countries of the world. Percentages of Covid-19 vaccination coverage must be increased in most countries of the world to increase individual and herd immunity levels in the population.

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M^Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M^Pro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae M^Pro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of M^Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M^Pro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M^Pro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 M^Pro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) that never terminate. For every j \in {1,2,3}, if Hypothesis j is true, then sem_j endlessly prints consecutive positive integers starting from 1. For every j \in {1,2,3}, if Hypothesis j is false, then sem_j prints a finite number (including zero) of consecutive positive integers starting from 1.

Abstract Background: Occipital neuralgia is a debilitating condition and traditional treatments often provide limited or temporary relief. Recently, ultrasound-guided hydrodissection of the greater occipital nerve (GON) has emerged as a promising minimally invasive approach. Objectives: To describe two novel ultrasound-guided hydrodissection with 5% dextrose for GON and discuss their advantages, disadvantages, and considerations. Methods: Two case reports are presented. Case 1 describes a lateral decubitus approach for hydrodissecting the GON between the semispinalis capitis (SSC) and obliquus capitis inferior (OCI) muscles. Case 2 details a cranial-to-caudal approach for hydrodissecting the GON within the SSC and upper trapezius (UT) muscles when the GON pass through these two muscles. Results: Both patients experienced significant and sustained pain relief with improvements in function and quality of life. Conclusions: Ultrasound-guided GON hydrodissection using 5% dextrose is a promising treatment for occipital neuralgia. The lateral decubitus and cranial to caudal approaches provide additional options to address patient-specific anatomical considerations and preferences.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Various attempts to amplify an AQP11 cDNA from tissues of the spiny dogfish (Squalus acanthias) were made. Two pairs of deoxy-inosine-containing degenerate primers were designed based on conserved amino acid sequences from an AQP11 alignment. These primers yielded some faint bands from gill cDNA that were sequenced. Blast searches with the sequences showed they were not AQP11. An elasmobranch AQP11 nucleotide sequence alignment was produced to identify conserved regions to make further degenerate primers. One primer pair produced a short 148bp fragment showing particularly strong expression in gill and intestine. It was sequenced and represented a piece of the AQP11 gene. However, as the fragment may have resulted from contaminating genomic DNA (in total RNA used to make cDNA), 5’ and 3’ RACE was performed to amplify the two ends of the putative cDNA. 5’ and 3’ RACE amplifications depend on the presence of a 5’ cap nucleotide and a poly A tail respectively on the putative AQP11 mRNA. Hence successful amplification was only possible from cDNA and not genomic DNA. Nested RACE amplifications were performed using gill and intestinal RACE cDNA but none of the DNA fragments were AQP11. Consequently, the spiny dogfish AQP11 gene may represent a pseudogene.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Background: In the heart, aldosterone (Aldo) binds the mineralocorticoid receptor (MR) to exert damaging, adverse remodeling-promoting effects. We recently showed that G protein-coupled receptor (GPCR)-kinase (GRK)-5 blocks the cardiac MR by directly phosphorylating it, thereby repressing its transcriptional activity. MR antagonist (MRA) drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure. Non-steroidal MRAs, such as finerenone, may provide better cardio-protection against Aldo than classic, steroidal MRAs, like spironolactone and eplerenone. Herein, we sought to investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade. Methods: We used the cardiomyocyte cell line H9c2 and neonatal rat ventricular myocytes (NRVMs). Results: GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone. Unlike eplerenone, finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity, thus displaying inverse agonism. GRK5 is necessary for finerenone`s inverse agonism, since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity. Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels. Finally in NRVMs, GRK5 is necessary for the anti-apoptotic and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis and fibrosis. Conclusions: Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart. GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

Background: In recent years, undernutrition has remained a significant public health issue in Tu-nisia, increasing the risk of illness and mortality in young children. Therefore, this study aims to analyse the prevalence and factors contributing to undernutrition among Tunisian children aged 0-23 months; Methods: The study included 3265 children aged 0-23 months from the 2011-2023 Tunisia Multiple Indicator Cluster Surveys (MICS). Trends and logistic regression analyses were used to determine the prevalence and predictors of undernutrition; Results: The prevalence of stunting, wasting, and underweight in infants and children aged 0-23 months has increased by 3.3%, 0.5%, and 2.1%, respectively. Stunting and underweight were more common among infants aged 0-5 months (11.8% for stunting, 8.9% for underweight, p < 0.01), and first-time mothers (8.3% for stunting, 4.1% for underweight, p < 0.01). In 2023, compared to 2011, the odds of stunt-ing, wasting, and being underweight have increased by 22%, 16%, and 70% respectively. Infants aged 0-5 months had higher odds of undernutrition in all three indices. Children of obese or overweight mothers, and those who started breastfeeding late, were more likely to be stunted. Boys had significantly higher odds of wasting and underweight. Small birth weight, and dura-tion of breastfeeding > 12months had significantly higher odds of being underweight; Conclu-sions: This study shows that infants aged 0-5 months, first-time mothers, boys, and children from poor households in Tunisia are at a higher odd of undernutrition. To address the growing issue of undernutrition in Tunisian children, enhancing maternal and child health and nutrition ser-vices, improve parental education, and implement community-based programs that provide breastfeeding and nutritional education to infants born to new mothers and mothers with high/low BMI is recommended.

Background/Objectives: COVID-19 led to a pandemic that has brought misery to millions of people but more so to those with pre-existing conditions. For this infection, several antiviral drugs were employed, including remdesivir (R) and paxlovid [nirmatrelvir/ritonavir (NR)]; Methods: The current study compared the effectiveness of remdesivir and paxlovid treatment for COVID-19 patients with comorbid conditions. Data from a cohort of 151 adult patients with COVID-19 who also had associated comorbidities were used in this study. These patients were treated with antivirals according to local guidelines. The subjects included 78 case-patients assigned to group R and 73 to group NR; Results: In group NR, a considerable improvement in oxygen saturation was seen in the first 24 hours of treatment (p=0.010), but the levels were significantly higher from the second day of treatment (p &lt;0.001) in group R of patients. At the end of the 5 days of treatment, the oxygen saturation improved statistically significantly compared to the admission day, but only in the R group (95.11±1.80; 91.76±1.80; p&lt;0.001); Conclusions: Both drugs can be considered a breakthrough in the current treatment approach to the COVID-19 disease since they provide readily available options that can alleviate the severity of the disease and, hence, the prognosis of patients. That is why their effectiveness relies on the correct administration time and choosing the patient with suitable characteristics regarding the presence of comorbidities and the likelihood of the critical further development of the process.

Introduction: The aim of this study is to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. Material and Methods: Prospective case-control study. Data collection period was between May 2020-2022. 80 tracheostomies on patients with long intubation were performed and the resected tracheal ring was examined by standard microscopy. 40 consecutive tracheotomies in COVID-19 patients and 40 in patients without COVID-19 disease were carried out. Results: The mean age was 68.18 years in the COVID group and 56.1 years in the NO COVID group. The male/female ratio was 32/8 versus 29/11 respectively. No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented vasculitis (2,5%) and one case thrombotic microangiopathy (1,2%), all cases in the COVID group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2=0.779) no significant indices for measuring association (Rho= 0.1316) and no significant risk indices (RR = 1.8, OR=2.032, PAR= 44%). Conclusion: There is no evidence of increased risk of histopathological findings of the resected tracheal ring in patients with long intubation and COVID-19 disease.

In this paper, a new way to obtain photoactive cements was presented. In this method amorphous TiO2 is added to cooler during the cooling of the cement clinker (Górażdże company) during cement production. Amorphous TiO2 was taken from the installation for obtaining titanium dioxide using the sulphate method. During the studies amorphous TiO2 was added to clinker at different temperature 300, 600, 700 and 800 °C. The properties of the obtained cement were tested during the bending and compressive strength and beginning and the end of bending setting time measurements. The adhesion of the obtained materials to concrete block, ceramic brick and plasterboard were also evaluated. The photocatalytic activity of the obtained materials was studied during NO and BTEX (benzene, toluene, ethylbenzene, p-,m-,o-xylenes decomposition) decomposition. Cement with 5 wt.% TiO2 added to clinker at 700 C had the highest photocatalytic activity and the best mechanical properties.

Introduction: Healthcare workers (HCW) are at higher risk of SARS-CoV-2 infection. Viral surveillance for early detection of COVID-19 is a critical strategy to understand the infection dynamics in this population and to prevent transmission. The study examines SARS-CoV-2 infection and reinfection among HCW vaccinated against COVID-19 who are employed at a primary health care unit serving a disenfranchised community of Brazil. Methods: The study was conducted in Cidade Estrutural, Federal District of Brazil, between February and October 2021. Participants were interviewed and provided samples. A prospective open cohort study was used to analyze the frequency of SARS-CoV-2 infection and reinfection. Nasopharyngeal and peripheral blood samples were collected from workers presenting with flu-like symptoms and subjected to RT-qPCR and serological testing (IgM and IgG chemiluminescence). The frequencies of infection and reinfection (RT-qPCR positive results 90 days after the infection) were calculated along with their respective confidence intervals (95%CI). Results: Of the 128 workers, 61 (47.65%; CI: 39.19-56.25) reported probable SARS-CoV-2 infection before vaccination. Of these, 50 (39.06%; CI: 31.04-47.71) had SARS-CoV-2 infection after vaccination, confirmed by molecular tests. Reinfection was identified in seven workers (14.00%; CI: 6.95-26.18), based on the 90-day interval between results. The serological data from the 128 workers during the cohort indicated that 68 had IgG antibodies (53.12%; CI: 44.5-61.5) and 46 had IgM antibodies (35.93%; CI: 28.14-44.54) against SARS-CoV-2. SARS-CoV-2 infection was common in community health workers (CHW, 56%), registered nurses (50%), and licensed practice nurses (33%). Following the COVID-19 vaccination, the percentage of infections among CHW decreased from 47.83% to 4.35%. Conclusion: These results demonstrate that (i) approximately 40% of the workers were infected with SARS-CoV-2 in 2021 and (ii) reinfections confirmed by RT-qPCR occurred in 14% of the HCW after vaccination. The results provide valuable insights into the circulation of SARS-CoV-2 among HCW in a primary care unit serving a minoritized community.

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported even in specialized centers. Mobile health technologies have been used in research settings to overcome these limits with contrasting results. This study aims to evaluate the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Patients were randomly assigned to standard care or standard care plus mobile app (2:1). The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: Seventy-five subjects were prospectively enrolled. At six months of follow-up, the m-app group showed significantly lower dropout rates compared to standard care(p=0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86,95%C.I. 1.39-10.42,p=0.01). After one year of follow-up, we observed lower albeit non statistically significant dropout rates in the m-app compared to the standard care group(p=0.24). No differences were observed in terms of z-score BMI and percentage of BMI reduction between the two groups. Conclusion: our findings suggest that mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction.

Testicular cancer accounts for approximately 1% of adult cancers and 5% of all urologic cancers. The most common histopathological diagnosis of testicular neoplastic lesions are germ cell tumors (90-95% of cases), among which the majority of cases are seminomas, the most common malignant tumors among men aged 15-44. For better clinical diagnosis and treatment, it is important to understand the molecular mechanisms of tumor formation. In this study, the expression of the CacyBP/SIP protein and ERK1/2 and p38 kinases was analyzed for the first time in seminomas and normal testicular tissues. The research was carried out using archival tissue material from 30 patients undergoing surgery due to testicular seminoma, whereas the comparative material consisted of the adjacent normal tissues. Immunohistochemistry and qRT-PCR were used to identify the expression of CacyBP/SIP, ERK1/2, and p38. A very clear weakening of both immunoreactivity and gene expression of all tested parameters was demonstrated in seminomas compared to healthy tissues. Our findings suggest the involvement of the CacyBP/SIP protein in the ERK1/2 and p38 signalling pathways, which may be involved in the processes of testicular seminoma carcinogenesis. The results of our research provide the basis for further research in this area.

Long COVID-19 affects a significant percentage of survivors and is characterized by a wide range of symptoms, including weariness and mental fog as well as emotional symptoms like worry and sadness. COVID-19 is closely linked to the autoimmune disorders that are becoming more prevalent worldwide and are linked to the immune system hyperactivation, neutrophil extracellular trap (NET) development, and molecular mimicry pathways. Long-term COVID-related autoimmune responses include a watchful immune system, altered innate and adaptive immune cells, autoantigens secreted by living or dead neutrophils, and high concentrations of autoantibodies directed against different proteins. The microbiome, which consists of billions of bacteria living in the human body, is essential for controlling immune responses and supporting overall health. The microbiome can affect the course of long-term COVID-associated autoimmunity, including the degree of illness, the rate of recovery, and the onset of autoimmune reactions. Although the precise role of the microbiome in long COVID autoimmunity is still being investigated, new studies indicate that probiotics, prebiotics, and dietary changes—interventions that target the microbiome—may be able to reduce autoimmune reactions and enhance long-term outcomes for COVID-19 survivors. It is clear that more research is required to precisely understand how the microbiome affects COVID-19-related autoimmunity and to create tailored treatment plans.

Background: Post-acute sequelae of SARS-CoV-2 infection (PASC) is a complicated disease that affects millions of people all over the world. Previous studies have shown that PASC impacts 10% of SARS-CoV-2 infected patients of which 50-70% are hospitalized. It has also been shown that 10-12% of those vaccinated against COVID-19 were affected with PASC and its complications. The severity and the later development of PASC symptoms is positively associated with the early intensity of the infection. Results: The generated health complications caused by PASC involve a vast variety of organ systems. Patients affected by PASC have been diagnosed with neuropsychiatric and neurological symptoms. Cardiovascular system also has been involved and several diseases such as myocarditis, pericarditis, and coronary artery diseases were reported. Chronic hematological problems such as thrombotic endothelialitis and hypercoagulability were described as a condition that could increase the risk of clotting disorders and coagulopathy in PASC patients. Chest pain, breathlessness, and cough in PASC patients were associated with respiratory system in long COVID-19 causing respiratory distress syndrome. The observed immune complications were notable, involving several diseases. Renal system also was impacted and result in raising the risk of diseases such as thrombotic issues, fibrosis, and sepsis. Endocrine gland malfunction can lead to diabetes, thyroiditis, and male infertility. Symptoms such as diarrhea, nausea, loss of appetite and taste were also among reported observations due to several gastrointestinal disorders. Skin abnormalities might be an indication of infection and long-term implications such as persistent cutaneous complaints were linked to PASC. Conclusions: Long COVID is a multidimensional syndrome with considerable public health implications, affecting several physiological systems and demanding thorough medical therapy as well as more study to address its underlying causes and long-term effects.

Our investigation focused on the degradation of perfluorooctanoic acid (PFOA) and 6:2 fluorotelomer sulfonamide alkyl betaine (6:2 FTAB, Capstone B), using UV photolysis under various pH conditions. Initially, we used PFOA as a reference, finding a 90% decomposition after 360 minutes at the original (unadjusted) pH 5.6, with a decomposition rate constant of (1.08 ± 0.30) × 10-4 sec-1 and a half-life of 107 ± 2 minutes. At pH 4 and 7, degradation averaged 85% and 80%, respectively, while at pH 10, it reduced to 57%. For 6:2 FTAB at its natural pH 6.5, almost complete decomposition occurred. The primary UV transformation product was identified as 6:2 fluorotelomer sulfonic acid (6:2 FTSA), occasionally accompanied by shorter-chain perfluoroalkyl acids (PFAA). Interestingly, the overall decomposition percentages were unaffected by pH for 6:2 FTAB, though pH influenced rate constants and half-lives. In PFOA degradation, direct photolysis and reaction with hydrated electrons were presumed mechanisms, excluding the involvement of hydroxyl radicals. The role of superoxide radicals remains uncertain. For 6:2 FTAB, both direct and indirect photolysis were observed, with potential involvement of hydroxyl, superoxide radicals, and/or other reactive oxygen species (ROS). Clarification is needed regarding the role of eaq- in the degradation of 6:2 FTAB.

2-Pyridone ligand-facilitated palladium-catalyzed direct C–H bond functionalization via the transient directing group strategy has become an attractive topic. Here we report a Pd-catalyzed direct β-C(sp3) –H arylation reaction of tertiary aliphatic aldehydes by using an α-amino acid as a transient directing group in combination with a 2-pyridone ligand.

Several questions regarding the evolution of SARS-CoV-2 remain poorly elucidated. One of these questions is the possible evolutionary impact of SARS-CoV-2 after the infection in domestic animals. In this study, we aimed to evaluate the potential role of cats as generators of relevant SARS-CoV-2 lineages during the pandemic. A total of 105 full-length genome viral sequences obtained from naturally infected cats during the pandemic were evaluated by distinct evolutionary algorithms. Analyses were enhanced, including a set of highly related SARS-CoV-2 sequences recovered from human populations. Our results showed the apparent high susceptibility of cats to the infection SARS-CoV-2 compared with other animal species. Evolutionary analyses indicated that the phylogenomic characteristics displayed by cat populations were influenced by the dominance of specific SARS-CoV-2 genetic groups affecting human populations. However, disparate dN/dS rates at some genes between populations recovered from cats and humans suggested that infection in these two species may suppose a different evolutionary constraint for SARS-CoV-2. Interestingly, the branch selection analysis showed evidence of the potential role of natural selection in the emergence of 5 distinct cat lineages during the pandemic. Although these lineages were apparently irrelevant to public health during the pandemic, our results suggested that additional studies are needed to understand the role of other animal species in the evolution of SARS-CoV-2 during the pandemic.

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization.Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for ancestral and Delta strains. A total of 6,683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to unvaccinated, receiving ≥2doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]), and PT80 for ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally, and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1,261 T2D patients and 1,105 control individuals. Our findings revealed significant associations between certain single nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p<0.001), m.14766C>T (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p<0.001), and m.16519T>C (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p=0.012) were significantly associated with diabetes probability. The variant m.16189T>C Previously reported in multiple studies in different populations, it was not found to be associated with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31,; p=0.83). These results provide evidence suggesting a link between some mtDNA polymorphisms and T2D, probably related to association rules and topological patterns and three-dimensional confirmation associated to regions where the changes are, rather than to point mutations in the sequence.

The collective considerations presented here lead to a crucial question: What truly constitutes the primary public health challenge posed by SARSCoV-2 infection and its variants?The findings of Bowen et al.(1) and Noé et al.(4) have offered us new insights into the actual repercussions of SARSCoV-2 virus infections on public health. They unmistakably point to the late sequelae and complications arising as secondary effects of the viral infection, causing severe and long-term damage to global public health. Rather than the acute infection which has a very low mortality rate in the general population, as initially and commonly believed.

Rhabdomyolysis is a serious clinical condition, which if left untreated can lead to kidney failure and in extreme cases, to death. It has also been reported in association with SARS COV2 infection and can be its initial presentation. COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), which has many variants that change the characteristics of the disease affecting, among other things, the method of transmission or treatment. Some investigators have implicated excessive immune response in the causes of muscle damage during SARS-CoV-2 infection. Others point to direct damage caused by the virus or involving immune factors. In this study we described cases of COVID-19 infection from 1 June 2022 to 15 July 2022 with elevated muscle enzymes in the blood and hospitalized to the first division of Cotugno hospital in Campania. Of 39 patients with SARS-CoV-2 infection, 15 patients presented also rhabdomyolysis. The most common symptoms were: asthenia, fever, arthomyalgia, lipothymia and syncope. No patient had myocardial infarction and 2 patients had atrial fibrillation. All patients were affected by omicron SARS-CoV-2 variants. Of these patients: 4 patients died (2 due to rhabdomyolysis and 2 due to sepsis) and only one patient presented acute kidney injury.

Purpose Isocitrate dehydrogenase (IDH) mutation has become one of the most important prognostic biomarkers in glioma management, indicating better treatment response and prognosis. IDH mutations confer neomorphic activity leading to the conversion of alpha-ketoglutarate (α-KG) to 2-hydroxyglutarate (2HG). The purpose of this study was to investigate the clinical potential of proton MR spectroscopy (1H-MRS) in identifying IDH-mutant gliomas by detecting characteristic resonances of 2HG and its complex interplay with other clinically relevant metabolites. Materials and Methods Thirty-two patients with suspected infiltrative glioma underwent single-voxel (SVS, n=17) and/or single-slice multivoxel (1H-MRSI, n=15) proton MR spectroscopy (1H-MRS) sequence with an optimized echo-time (97ms) on 3T-MRI. Spectroscopy data were analyzed using linear combination (LC) model. Cramer-Rao lower bound (CRLB) values of <40% were considered acceptable for detecting 2HG and <20% for other metabolites. Immunohistochemical analyses for determining IDH mutational status were subsequently performed from resected tumor specimens, and findings were compared with the results from spectral data. Mann-Whitney and Chi-squared tests were performed to ascertain differences in metabolite levels between IDH-mutant and IDH-wild-type gliomas. Receiver operating characteristics (ROC) curve analyses were also performed. Results Data from eight cases were excluded due to poor spectral quality or non-tumor-related etiology, and final data analyses were performed from 24 cases. Of these cases, 9/12 (75%) were correctly identified as IDH-mutant or IDH-wildtype gliomas by SVS and 10/12 (83%) by 1H-MRSI with an overall concordance rate of 79% (19/24). The sensitivity, specificity, positive predictive value, and negative predictive values were 80%, 77%, 86%, and 70%, respectively. The metabolite 2HG was found to be significant in predicting IDH-mutant gliomas by Chi-squared test (p<0.01). The IDH-mutant gliomas also showed significantly higher NAA/Cr ratio (1.20 ± 0.09 versus 0.75 ± 0.12 p= 0.016) and lower Glx/Cr ratio (0.86±0.078 versus 1.88±0.66; p=0.029) than those with IDH wild-type gliomas. The areas under the ROC curves for NAA/Cr and Glx/Cr were 0.808 and 0.786, respectively. Conclusion 1H-MRS may be useful in detecting IDH mutational status in gliomas by detecting 2HG and characteristic patterns of other metabolite ratios (NAA/Cr and Glx/Cr). This has significant clinical implications for prognostication and response assessment to novel targeted therapies in gliomas.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community leading to the development, study, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this paper, we posit essential points on SARS-CoV-2 and its management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers who directly communicate with patients and serve as role models for healthy behaviors.

(1) Background: Since the onset of the SARS-CoV-2 pandemic, seven epidemic waves have been described in Spain. Our objective was to study mortality and severity, and associated factors in our hospitalized patients; (2) Method: Retrospective cohort study was conducted on COVID-19 patients admitted to the Hospital de Fuenlabrada (Madrid, Spain) from the beginning of the pandemic until December 31, 2022; (3) Results: A total of 5,510 admissions for COVID-19 were recorded. First wave accounted for 1,823 (33%) and exhibited the highest proportion of severe patients (lowest mean oxygen saturation, 88.2%; elevated levels of CRP, IL-6, D-dimer and ferri-tin), but a below-average percentage of intubated patients (5% vs. 6.5%). Overall mortality rate was 10.3%, higher during the first wave (11.5%) and the two winter waves (third: 11.3%, sixth: 12%), although the first wave represented 39% of the total. Variables associated with mortality were age (OR 1.08,1.07-1.09), need for high-flow oxygen (OR 6.10,4.94-7.52), oncological disease (OR 1.88,1.53-2.60), dementia (OR 1.82,1.2-2.75), Charlson index (OR 1.38,1.31-1.47), and maxi-mum IL-6 levels (OR 1.001,1.000-1.001); (4) Conclusions: Variables associated with mortality in-cluded age, comorbidity, respiratory failure, and inflammation. Differences on baseline charac-teristics of patients admitted explained differences on mortality in each wave

The COVID-19 pandemic has become the largest public health crisis since the 1918 influenza pandemic. Despite the extensive research conducted on the SARS-CoV-2 virus in humans, little is still known about animal-related transmission and its consequences. Therefore, this study contributed to a better understanding of this issue by focusing on the serological survey of SARS-CoV-2 in samples from the serum bank of the Bovine Virology Laboratory at the Biological Institute of São Paulo, as well as horses and dogs from the Military Police of the State of São Paulo, and tapirs and bats from the states of Mato Grosso do Sul and São Paulo. To achieve this, the possible presence of anti-SARS-CoV-2 antibodies in domestic and wild animal species was evaluated using the ID Screen® "SARS-CoV-2 Double Antigen Multi Species" ELISA test (ID-Vet.®), following the manufacturer's recommendations. The findings of this study demonstrate a higher occurrence of anti-SARS-CoV-2 antibodies in domestic animals compared to wild animals, as well as different antibody profiles among the species analyzed, with horses showing a wide range of seroconversion comparable to humans.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA Hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed pre-COVID-19 pandemic (2015 to 2019) and during the pandemic (2020 - 2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from 10/2019 – 3/2022. CDI case numbers declined 43.2% in 2020 – 2021 compared to the annual mean over the previous 5 years. Stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; P = 0.013). Although inpatient volume declined, rates of CDI among inpatients were reduced by 34.2% in 2020 – 2021. Mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89 – 3.87) vs. 1.92 (95% CI: 1.27 – 2.56); P = &lt;0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic from March 8, 2020, through June 30, 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%. After adjusting for CDI risk factors, a multivariable logistic regression model revealed that odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03 – 39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the initial waves of the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain and frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic.

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has executed 6.9 million people and infected over 765 million. It’s become a major worldwide health alarm and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower res-piratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse out-comes. Prophylactic anticoagulation is essential to prevent complication and death rate associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation exhibits some similarities to DIC induced by sepsis. LDH, D-dimer, ferritin, and CRP biomarker are often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas is a characteristic feature of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.

We hypothesize the possible route of introduction of the cosmopolitan DENV-2 genotype into Brazil through the border with Peru. The five sequences presented in this study create a geographical link with the three others sequences of this genotype already recorded on the continent.

A key component of efforts to identify the biological and drug-specific aspects that contribute to therapeutic failure or unexpected exposure-associated toxicity is the study of drug-intestinal barrier interactions. While methods supporting such assessments are widely described for human therapeutics, there is relatively little information available for similar evaluation in support of veterinary pharmaceuticals. There is, therefore, a critical need to develop novel approaches for evaluating drug-gut interactions in veterinary medicine. Three-dimensional (3D) organoids can address these difficulties in a reasonably affordable system that circumvents the need for more invasive in vivo assays in live animals. However, a first step in the development of such systems is understanding organoid interactions in a 2D monolayer. Given the importance of orally administered medications for meeting the therapeutic need of companion animals, we demonstrate growth conditions under which canine colonoid-derived intestinal epithelial cells survive, mature, and differentiate into confluent cell systems with high monolayer integrity. We further examine the applicability of this canine colonoid-derived 2D model to assess the permeability of three structurally diverse, passively absorbed β-blockers (e.g., propranolol, metoprolol, and atenolol). Both absorptive and secretive apparent permeability (Papp) of these drugs at two different pH conditions were evaluated in canine colonoid-derived monolayers and were compared with that of Caco-2 cells. This proof-of-concept study provides promising preliminary results with regard to the utility of canine-derived organoid monolayers for species-specific assessments of therapeutic drug passive permeability.

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and mortality associated with it. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccinations, primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.