Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

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.

Long Covid has many symptoms that overlap with ME(myalgic encephalomyelitis)/CFS(chronic fatigue syndrome), FM(fibromyalgia), EBV(Epstein-Barr virus), CMV(cytomegalovirus), CIRS (chronic inflammatory response syndrome), MCAS(mast cell activation syndrome), POTS(postural orthostatic tachycardia syndrome), and post viral fatigue syndrome. They all portend a “long haul” with an antioxidant shortfall and elevated Ca:Mg. Oxidative stress is the root cause. Linkage between TGF(transforming growth factor)-β, IFN(interferon)-γ, the RAS(renin angiotensin system), and the KKS(kallikrein kinin system) is discussed. Technical explanations for the renin aldosterone paradox in POTS, the betrayal of TGF-β, and the commonality of markers for the Warburg effect are offered. The etiology of the common Long Covid symptoms of post exertional malaise, fatigue, and brain fog as well as anosmia, hair loss, and GI symptoms is technically discussed. Ca:Mg is critical to the glutamate/GABA balance. The role of GABA and butyrates from the “good” intestinal bacteria in the gut-brain axis and its correlation with chronic fatigue diseases are explored. The crosstalk between the ENS(enteric nervous system) and the ANS(autonomic nervous system) and the role of the vagus in both are emphasized. HRV(heart rate variability), the fifth vital sign, points to an expanded gut-brain-heart/lung axis. A suggested approach to all of these - Long Covid, chronic fatigue diseases, post viral fatigue syndrome, and general health - is presented.

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.

Brain fog with compromised ability to concentrate has been the most frequent Long Covid (LC) complaint. This is due to an increased transforming growth factor (TGF) β/interferon (IFN)-γ ratio with consequently increased bradykinin (BKN), especially in Caucasian females. Brain and lung blood vessels “leak.” This same ratio is increased in Alzheimer’s disease (AD), but decreased in Parkinson’s disease (PD), because CD4⁺ and CD8⁺ T cells are differentially affected by the invading associated viruses, e.g., SARS CoV2, HIV, Varicella Zoster (VZV) aka Human Herpesvirus 3 (HHV3), HBV, HCV, …. In Covid-19 CD147 receptors on immune cells are critical in generating the increased TGF-β/IFN-γ and those on endothelial cells, platelets, and erythrocytes are critical to the abnormal microvascular blood flow. ACE2 receptors on pneumocytes and enterocytes enable pulmonary and GI entry, initiating gut dysbiosis. Epigenetics, methylation, magnesium, vitamin D, the B vitamins, and antioxidants suggest that these issues can be surmounted. Biochemical, physiologic, and epidemiologic data are analyzed to answer these questions. An LC model is presented and discussed in the context of the most recent research. Suggestions to avoid these and other worrisome concerns are included. Other topics discussed include estrogen, the gut microbiome, type 2 diabetes (T2D), and homocysteine.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p < 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

Many people in the USA have lost their lives or become addicted to opioids via prescription opioids given for chronic pain. The chronic pain epidemic has emerged due to a convergence of factors, including the medicalization of pain as well as injuries happening in the workplace, in the home, or during recreation. Opioid prescriptions rose precipitously from the late 1990’s through to approximately 2020, and despite public awareness, still are increasing. This review examines literature on integrative approaches to chronic pain as delineated by pain type. The review is organized by the most common causes of chronic pain, and randomized controlled trials, meta-analyses and systematic reviews are extracted for each cause of chronic pain. Several promising interventions may alleviate chronic pain of some causes, and some interventions may work across pain causes. Lowering inflammation through dietary or lifestyle regimens may be a general way of reducing pain. Pain can be alleviated through several adjunctive and integrative treatment approaches, which may serve to lower the need for opioid medication.

This narrative review examines the crucial role of physical activity in managing long COVID, characterized by persistent symptoms such as fatigue, breathlessness, and cognitive impairments following SARS-CoV-2 infection. The methodology involved a comprehensive literature search across PubMed, EBSCO (EDS), and Google Scholar, selecting peer-reviewed articles from December 2019 focusing on long-term COVID physical activity interventions. The review highlights that tailored exercise programs, adjusted to individual health status and abilities, significantly alleviate symptoms and enhance psychological well-being. Key findings emphasize the importance of personalized exercise prescriptions due to the variability in patient responses and the need for a multidisciplinary approach in developing and monitoring interventions. Despite promising outcomes, the review identifies research gaps, including the need for long-term studies, randomized controlled trials, and deeper mechanistic insights. It suggests that standardized reporting, templates like CERT, and integrating digital health tools are essential for optimizing interventions. Overall, the review advocates including personalized physical activity programs in standard care for long COVID to improve patient outcomes and quality of life.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.

This study explores the role of inflammation and oxidative stress, hallmarks of COVID-19, in accelerating cellular biological aging. We investigated early molecular markers—DNA methylation age (DNAmAge) and telomere length (TL)—in blood leukocytes, nasal cells (NC), and induced sputum (IS) one-year post-infection in pauci- and asymptomatic healthcare workers (HCWs) infected during the first pandemic wave (February-May 2020), compared to COPD patients, model for "aged lung". Data by questionnaires, Work Ability Index (WAI), blood analyses, autonomic cardiac balance assessments, heart rate variability (HRV), and pulmonary function tests were collected. Elevated leukocyte DNAmAge significantly correlated with advancing age, male gender, daytime work, and an aged phenotype characterized by chronic diseases, elevated LDL and glycemia levels, medications affecting HRV, and declines in lung function, WAI, lymphocyte count, hemoglobin levels, and HRV (p<0.05). Increasing age, LDL levels, job positions involving intensive patient contact, and higher leukocyte counts collectively contributed to shortened leukocyte TL (p<0.05). Notably, HCWs exhibited accelerated biological aging in IS cells compared to both blood leukocytes (p≤0.05) and NC (p<0.001), and were biologically older than COPD patients (p<0.05). These findings suggest the need for monitoring aging in pauci- and asymptomatic COVID-19 survivors, who represent the majority of the general population.

Hypertension is a global public health challenge, with a high prevalence across various regions and significant implications for cardiovascular risk. This article reviews the effectiveness of herbal medicine as a potential therapeutic approach for hypertension, offering an alternative or complementary solution to conventional pharmacological treatments. It highlights several natural agents that have demonstrated efficacy in lowering systolic blood pressure (SBP) in clinical and meta-analytical studies. The methodology involved a systematic review of articles that discuss herbal therapeutics for hypertension, focusing on their efficacy compared to placebo and standard treatments. The findings suggest that certain nutraceuticals, such as garlic, hawthorn, and CoQ10, can significantly reduce SBP, presenting a viable option for managing hypertension. This review underscores the need for further research to validate these findings and optimize herbal treatment strategies, potentially expanding the use of these natural products in clinical practice. The article aims to increase awareness among medical professionals and patients about the benefits and applications of herbal medicines in treating hypertension.

Long Covid has become a blight, its economic consequences overwhelming. But Long Covid (LC) may represent persistent Covid-19 in those with preexisting Candida overgrowth (CO). The features shared by both are striking. LC may be a growing subset of CO. The altered tryptophan metabolism encountered in LC is driven by IFN-γ in reaction to CO. Females are robust producers of IFN-γ, yet estrogen promotes CO.The consequent decline in serotonin and melatonin triggers the mood swings and sleeplessness respectively in LC. The low serotonin, the primary messenger in the gut brain axis, creates autonomic dysfunction. The CO induced gut dysbiosis and leaky gut initiate an autoimmune path. TNFα seen in both LC and this opportunistic yeast is at the center of the cytokine triad that leads to neurodegeneration. The Western diet, high in carbohydrates, alcohol, and glutamate, is exploited by this commensal turned parasite. Residual SARS CoV2 and Candida generate abundant ROS, inducing mitochondrial dysfunction. Alcohol tastes different for many with LC, because acetaldehyde requires functioning hepatic mitochondria. This article delves into the complex physiology and biochemistry that drive the symptoms of this conspicuous connection. Recent research has revealed innovative approaches that might address this global scourge, including D-mannose for the immune dysfunction and butyrate for the gut dysbiosis created by and seen in both LC and intestinal Candidiasis.

These three syndromes - long covid (LC), postural orthostatic tachycardia syndrome (POTS), and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - have many symptoms in common. The common denominator remains elusive. The blood brain barrier (BBB) has been a barrier not only to microbes and toxins but also to understanding pathogenetic links. There are several areas within the brain that have no BBB. These are known as circumventricular organs (CVOs) and their location relative to CNS nuclei that direct autonomic and neuroendocrine functions is provocative in the quest for pathogenesis. In addition the majority afflicted with LC and ME/CFS appear to be those with two MTHFR polymorphisms, present in over 50% of Americans. These polymorphisms elevate homocysteine. When homocysteine is combined with CVOs, the fog of POTS and its paradox are lifted. POTS may represent the intersection of LC and ME/CFS in those with the MTHFR gene (hypermethylation or 677TT). The gut microbiomes of LC and ME/CFS, deficient in butyrates, GABA, and diversity, are then linked with MTHFR genotype 677TT. Reactivation of neurotropic EBV and VZV, due to loss of surveillance by CD4+/CD8+ T cells, is seen as secondary. The oxidative stress generated by homocysteine, loss of glutathione, low fiber diet, and persistent chronic inflammation exhaust available mitochondria and, assisted by BKN and estrogen, exacerbate all the elements of these post viral fatigue syndromes.

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 (>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.

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC shares similarities with regards to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCA) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n= 48 FM and n= 46 LC) and volumetric absorptive micro sampling tips (VAMS, n= 39 FM and n= 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra was acquired using SERS with gold nanoparticles (AuNPs). Soft Independent Modelling of Class Analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNPs SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

Antidepressants are among the most used medications in the US, with significant deleterious effects on people’s well-being. At any given time, depression impacts approximately 1 in 10 Americans, causing wide and broad societal costs. Interest is developing for non-pharmacological treatments and preventative measures. We summarize the literature on non-invasive dietary and lifestyle approaches for treating depression, including recent work with the psychedelic treatment of depression. This review aims to inform future research and treatment programs for depression. This review provides an evidentiary summary of integrative therapeutic approaches for depression.

Long-haul COVID-19 illness first gained widespread recognition among social support groups and later in scientific and medical communities. This illness is mysterious as it affects COVID-19 survivors at all levels of disease severity, even younger adults and children. While the precise definition may be lacking, the defining symptoms are fatigue, dyspnea, and headache that last for months after hospital discharge. The less typical symptoms may include cognitive impairments, chest and joint pains, myalgia, smell and taste dysfunctions, cough, mood changes, and gastrointestinal and cardiac issues. Presently, there is limited literature discussing the possible pathophysiology, risk factors, and treatments in long-haul COVID-19, which the current review aims to address. In brief, long-haul COVID-19 may be driven by long-term lung and brain damage and unresolved inflammation from multiple sources. The associated risk factors may include female sex, more than five early symptoms, early dyspnea, and specific biomarkers like D-dimer. While only rehabilitation training has been useful for long-haul COVID-19, therapeutics repurposed from mast cell activation syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, and pulmonary fibrosis also hold potential. In sum, this review hopes to provide the current understanding of what is known about long-haul COVID-19.

On the 9th March 2020, the first patient with COVID-19 was admitted to ICU in the Royal Gwent Hospital, Newport, Wales. We prospectively recorded the rate of ICU admissions of 52 patients with COVID-19 over 60 days, focusing on the epidemiology of ethnicity and deprivation. Patients were 65% (34 of 52) male and had a median (IQR) age of 55 (48-62) years. Prevalent comorbidities included obesity (52%); diabetes (33%), and asthma (23%). COVID-19 hospital and ICU inpatient numbers peaked on days 23 and 39, respectively – a lag of 16 days. The ICU mortality rate was 33% (17 of 52). Black, Asian and Minority Ethnics (BAME) population represented 35% of ICU COVID-19 admissions (18 of 52) and 35% of deaths (6 of 17). Within the BAME group, 72% (13 of 18) were found to reside in geographical areas representing the 20% most deprived in Wales, versus 27% of Caucasians (9 of 33). Less than 5% of the population within the hospital catchment area are of BAME descent, yet they represent a disproportionately high proportion of patients with ICU admission and mortality suffering from COVID-19. The interplay between ethnicity and deprivation, which is complex, may be a factor in our findings. This in turn could be related to an increased prevalence of co-morbidities; higher community exposure; or genetic polymorphisms.

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin-system (RAS) is critically involved in their pathophysiology and is counterbalanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin-system (KKS). Considerable research interest with respect to COVID-19 treatment is, thus, currently directed towards the components of these systems. In an earlier study, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and partially excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized (HoP) COVID-19 patients and a sub-group of covalescent patients, while in the majority of the probands recovering from the disease these values had returned to normal. The data had been obtained using bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE, and they were supplemented by serum proteomics of the same patient cohort. We hypothesized that the data could be indicative of Long COVID, which had not been fully appreciated at the time of our study.; (2) Methods: The data were re-evaluated in the light of Long COVID. The recent literature on the RAS in COVID-19, antihypertensiva, and Long COVID was briefly reviewed.; (3) Results: While the levels of the BK serum degradation products should return to normal concentrations during convalescence, this was not true for some patients. This could be due to persisting liver problems, because CPN is synthesized there, but also to a dysregulated RAS. This was not reflected in the levels of selected RAS/KKS serum proteins like angiotensinogen (AGT), although AGT correlated with disease severity in HoP. However, standard tests in routine patient care in Long COVID often come back normal, and it may be that BK degradation is specific in some pathophysiologies. Moreover, the HoP group was sub-divided based on the serum protein profiles and COVID-19 severity.; (4) Conclusions: We point out two insights: 1) Sensitive technology such as omics methods might provide unexpected significant differences within the pre-defined patient groups of a clinical study. Those can only be explored, if the cohorts are large enough and properly matched with respect to the parameters known beforehand (e.g., age, gender, co-morbidities). 2) Results of the BK-reporter serum protease activity assay could be indicative of persisting liver problems and/or potentially of Long COVID. Clinical studies are required to test this hypothesis.

The neurologic effects of long-COVID are a therapeutic challenge. This article discusses the immunologic manifestations of long-COVID and proposes a non-androgenic, synthetic analog of dehydroepiandrosterone (DHEA), bromo-epi-androsterone (BEA), as a candidate for clinical trials for this exigent collection of neurologic conditions. Moreover, because there is an association between long-COVID and Alzheimer’s disease, the evaluation of BEA in long-COVID may serve as a proxy for its effect on neuroinflammatory biomarkers of Alzheimer’s disease that are shared with long-COVID.

The COVID-19 pandemic, declared in early 2020, is an unprecedented global health crisis, causing over 7.0 million deaths and ongoing challenges. While the pharmaceutical industry expedited vaccine development, mutant SARS-CoV-2 strains remain a major fear. Moreover, concerns regarding the long-term health repercussions of COVID-19-affected individuals persist since individuals affected by mild and moderate to severe SARS-CoV-2 infection experience long-term cardiovascular complications, liver dysfunction, pulmonary afflictions, kidney impairments, and most importantly neurocognitive deficits. In recent studies, we documented pathophysiological changes in various organs following the post-acute infection of mice with murine hepatitis virus-1 (MHV-1), a coronavirus, at both 7 days and 12 months after infection. One part of the body that can be drastically affected by SARS-CoV-2 is the skin. Studies have shown major changes in the skin post-acute SARS CoV-2 infection in humans. However, long-term dermatologic changes post-COVID have never been explored. For the first time, we show several cutaneous findings both at the acute stages and long-term post-infection of mice with MHV-1 coronavirus (a promising experimental model to study acute and long-COVID). Precisely, we found destruction of the epidermal layer, an increase in the number of hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of the sebaceous glands at the acute stages, along with thinning of the panniculus carnosus, as well as the adventitial layer, which corresponds well with studies in humans. In contrast, the cutaneous investigation in the long-COVID phase shows the absence of hair follicles from both the epidermal and dermal layers, the destruction of adipose tissues, and the devastation of the epidermal layer. Further, treatment of these mice with a 15 amino acid synthetic peptide, SPIKENET (SPK), which was effective in preventing Spike glycoprotein-1 binding with host receptors, as well as has a potent anti-inflammatory response to severe inflammatory stimulus) restored the loss of hair follicles and re-architected the epidermal and dermal layers. Additionally, destruction in fatty tissue in the infected mice was successfully restored post-treatment with SPK. These findings suggest that SARS-CoV-2 initiates the changes early post-infection, leading to devastating skin alterations in the long term which can be prevented by our newly identified peptide drug SPK.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

Background: Nutritional status and oxidative stress have been implicated in the pathogenesis and persistence of long COVID, but data in patients undergoing hemodialysis (HD) are limited. The present study aimed to investigate the association between pre-infection nutritional status, oxidative stress, and one-year long COVID persistence in HD patients. Methods: This prospective observational cohort study enrolled 115 HD patients with confirmed COVID-19. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score twice: before infection and three months post-infection. Oxidative markers included malondialdehyde (MDAs), ceruloplasmin, transferrin, and sulfhydryl groups. The endpoint was one-year long COVID persistence. Results: Moderate pre-infection CONUT scores were associated with heightened severe undernutrition risk (p < 0.0001), elevated MDAs (p < 0.0001), and reduced ceruloplasmin levels (p = 0.0009) at three months post-COVID-19 compared to light CONUT scores. Pre-infection CONUT score independently predicted post-COVID oxidative damage [OR 2.3 (95%CI 1.2; 4.6), p < 0.0001] and one-year long COVID persistence [HR 4.6 (95%CI 1.4; 9.9), p < 0.0001], even after adjusting for potential confounders. Conclusion: Moderate pre-infection undernutrition in patients undergoing HD associated with increased post-COVID oxidative stress intensity and heightened risk of one-year long COVID persistence.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

The signs and symptoms of Long COVID can be explained by a shortage of blood in the body and a resulting deficient blood flow through nearly all organs. This shortage arose during the acute phase of COVID19 by an increased breakdown of haematocytes, to which the liver responds by reducing the production of plasma. In order to prevent a too large decrease in haematocrit. In order to ensure the perfusion of organs that are directly necessary for survival, the body takes the emergency measure of diverting blood from other organs and tissues. The perfusion of the blood-producing organs is also affected by this distribution measure, which hinders the smooth recovery of the total blood volume. The body is stuck in this vicious circle: a shortage of circulating blood hinders the recovery of blood production. This explains the long duration of Long COVID. My proposed treatment of Long COVID focuses on the recovery of the correct volume of blood in the body of the right composition by the intravenous administration of donor blood products, starting with albumin concentrate. A trial treatment can be performed in any hospital without much additional preparations, and has a lower associated risk for the patient than analysing the total blood. A diagnosis ex juvantibus, by therapeutic response, is therefore preferable. I suspect that we will find a haematocrit value at the high extreme of the reference range, and an albumin value at the low extreme of the reference range in most Long COVID patients before the start of the treatment, because the liver can not keep up with the recovery of the red bone marrow.

Relationships of the three bryophyte lineages (liverworts, mosses, and hornworts) to vascular plants is a pivotal question in the study of origin and evolution of land plants. In recent decades, this question has been subject to intense phylogenetic analyses using morphological characters, multigene DNA sequences, and genome structural characters. A tentative consensus reached ten years ago suggested that bryophytes are a paraphyletic group, with liverworts being sister to all other land plants and hornworts being sister to vascular plants. However, several more recent nuclear phylogenomic studies have concluded that bryophytes represent a monophyletic group that is sister to vascular plants. A discussion is presented here on strengths and weaknesses of different types of characters (morphological traits, nucleotide sequences, and genome structural arrangements), and their suitability for resolving deep phylogenetic relationships. Moreover, several criteria for credible phylogenetic reconstruction are proposed. Strong statistical support for reconstructed relationships should be derived from high quality, independent characters selected for suitability to the particular question being addressed. The relationships inferred in a study should be congruent with those from as many other lines of phylogenetic evidence as possible. Any incongruities should be explicable by well-understood biological mechanisms. It is concluded that the relationships of the three bryophyte lineages to vascular plants should currently be viewed as unresolved. This is a difficult phylogenetic problem; the land plants underwent a rapid radiation a long time ago. Yet, further exploration of analytical methods and careful choice of characters should lead to eventual elucidation of diversification patterns among early land plants.

The COVID-19 pandemic has posed an unprecedented challenge to healthcare and the available solutions are unsatisfactory. Classical homeopathy may have a role to play in alleviating this burden. Covid cases treated with homeopathy was curated with the intention to provide basic information for further studies. The results are promising although far from being definitive. 367 patients considered were for statistical analysis, the mean age of the participants was 42.75 years, and males and females were 166 and 201 respectively. The mean follow-up period was 6.5 (SD 5.3) days, with a median of 1 homeopathic remedy used per case. 192 patients were diagnosed by RT–PCR, 111 by the WHO clinical criteria and 64 via retrospective antibodies. According to the WHO criteria, 255 were confirmed cases, 61 were probable cases, and 51 were suspected cases. It was seen that 73.8% of covid patients improved under homeopathic treatment, even those among severe disease 78.6%. Correlational analyses showed that presence of fever was associated with more likelihood of improvement and increasing age and a greater number of homeopathic remedies required in a case were associated negatively with improvement. However, it was seen that severe cases were more likely to improve under homeopathic treatment.

(1) Background: COVID-19 was responsible for the latest pandemic, shaking and reshaping healthcare systems worldwide. Its late clinical manifestations make it linger in medical memory as a debilitating illness over extended periods. (2) Methods: Recent literature was systematically analyzed to categorize and examine the symptomatology and pathophysiology of Long COVID across various bodily systems, including pulmonary, cardiovascular, gastrointestinal, neuropsychiatric, dermatological, renal, hematological, and endocrinological aspects. (3) Results: The review outlines the diverse clinical manifestations of Long COVID across multiple systems, emphasizing its complexity and challenges in diagnosis and treatment. Factors such as pre-existing conditions, initial COVID-19 severity, vaccination status, gender, and age were identified as influential in the manifestation and persistence of Long COVID symptoms. This condition is highlighted as a debilitating disease capable of enduring over an extended period and presenting new symptoms over time. (4) Conclusions: Long COVID emerges as a condition with intricate multi-systemic involvement, complicating its diagnosis and treatment. The findings underscore the necessity for a nuanced understanding of its diverse manifestations to effectively manage and address the evolving nature of this condition over time.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Background: Here, we investigated the inflammaging and physical performance in older adults before and after the COVID-19 pandemic. Methods: Women(n=18) and men(n=7) older were evaluated before the COVID-19 pandemic(PRE), 12 months after the lockdown(POST), and 10 months after resuming exercise training(POS-TR). Physical tests [gait speed(GS) and timed-up-and-go(TUG)]; muscle strength (handgrip-HG), and serum cytokine levels were assessed. Results: The older women showed higher GS and TUG at POST than PRE and POST-TR, besides lower HG at POST-TR than PRE, whereas older men exhibited lower HG at POST and POST-TR than PRE. Both groups presented (1)lower IL-10 and IL-12p70 values in contrast to higher IL-6/IL-10 and IL-8/IL-10 ratios at POST than PRE; (2)higher IL-10 values and lower IL-8/IL-10 ratio at POST-TR than POST; (3)higher IL-12p70/IL-10 ratio at POST-TR than PRE and POST. Particularly older women showed: (4)lower IL-6 values at POST and POST-TR than PRE; (5)lower IL-8 and IL-10 values at POST-TR than POST; (6)and higher TNF-α/IL-10 and IFN-γ/IL-10 ratios at POST than PRE and POST-TR. Significant correlations between the variables were found in both groups. Conclusion: During the COVID-19 pandemic, detraining and resumption of exercise training promoted distinct alterations in physical capacity and inflammaging among older women and older men population.

While the COVID-19 outbreak was reported to first originate from Wuhan, China, it has been declared as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 by WHO, and it has spread to over 180 countries by the time of this paper was being composed. As the disease spreads around the globe, it has evolved into a worldwide pandemic, endangering the state of global public health and becoming a serious threat to the global community. To combat and prevent the spread of the disease, all individuals should be well-informed of the rapidly changing state of COVID-19. In the endeavor of accomplishing this objective, a COVID-19 real-time analytical tracker has been built to provide the latest status of the disease and relevant analytical insights. The real-time tracker is designed to cater to the general audience without advanced statistical aptitude. It aims to communicate insights through various straightforward and concise data visualizations that are supported by sound statistical foundations and reliable data sources. This paper aims to discuss the major methodologies which are utilized to generate the insights displayed on the real-time tracker, which include real-time data retrieval, normalization techniques, ARIMA time-series forecasting, and logistic regression models. In addition to introducing the details and motivations of the utilized methodologies, the paper additionally features some key discoveries that have been derived in regard to COVID-19 using the methodologies.

Recurrent sunspot groups were studied by using the Debrecen Photoheliographic Data (DPD) which covers more than 40 years. For this task it is necessary to make unambiguous the identification of the returning solar active regions. It starts with an algorithmic listing of possible returns, then the candidates of the algorithmic identifications are checked by the unique HTML-feature of the DPD. The final check is the application of an asymmetric Gaussian function introduced in previous articles to describe the development of short-lived sunspot groups observed continuously from start to end on the visible solar disc. The data of correctly identified recurrent sunspot groups fit surprisingly well to this function throughout the rotations enabling the reconstruction of the development also on the far side of the sun. The primary goal was to find any relationship between the maximum area and the lifetime deduced from the data of the asymmetric curves. This relationship is more complex than earlier results in the literature for short-lived groups. The lifetimes exhibit weak dependencies on the heliographic latitude and solar cycle phase. An apparently returning active area is rather an active nest if its data do not fit to the asymmetric Gaussian.

The dermatological manifestations of Long Covid (LC) have languished in the shadows of chronic fatigue and brain fog. Yet they are all linked by gut dysbiosis and the cytokine triad of TNF-α, IL-1β, and IL-6. The gut microbiome common not only to LC, psoriasis, AA, and vitiligo but also to neurodegenerative disease has been recently described. This gut microbiome induces an altered tryptophan metabolism linked to autoimmune disease. SARS CoV2 invades enterochromaffin cells rich in ACE2 receptors and curtails absorption of the essential amino acid tryptophan and subsequent synthesis of serotonin and melatonin. This review suggests that an etiologic prebiotic (d-mannose)/probiotic (lactobacilli, bifidobacteria)/postbiotic (butyrate) approach to autoimmune skin disease that improves intestinal barrier integrity and that suppresses the triad of TNF-α, IL-6, and IL-1β may enhance or even eliminate the traditional immunotherapy of targeted monoclonal antibodies, Janus kinase inhibitors, and steroids. Health benefits of this approach extend well beyond suppression of autoimmune skin disease.

The increasing number of people living with Long COVID requires the development of more personalized care, as for now limited treatment options and rehabilitation programs adapted to the variety of Long COVID presentations are available. Our objective was to design an easy-to-use Long COVID classification to help stratifying people with Long COVID. Individual characteristics and a detailed set of 62 self-reported persisting symptoms together with quality of life indexes 12 months after initial COVID-19 infection were collected in a cohort of SARS-CoV-2 infected people in Luxembourg. A hierarchical ascendant classification (HAC) was used to identify clusters of people. We identified 3 patterns of Long COVID symptoms with a gradient in disease severity. Cluster-Mild encompassed almost 50% of the study population and was composed of participants with less severe initial infection, fewer comorbidities, and fewer persisting symptoms (mean=2.9). Cluster-Moderate was characterized by a mean of 11 persisting symptoms and a poor sleep and respiratory quality of life. Cluster-Severe was characterized by a higher proportion of women and smokers as in the other clusters, with a higher number of Long COVID symptoms, in particular of vascular, urinary, and skin symptoms. Our study evidenced that Long COVID can be stratified in 3 sub-categories in terms of severity. If replicated in other populations, this simple classification will help clinicians to personalize the care of people with Long COVID.

Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (&lt; 2,500 m) and high altitude (&gt;2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

Background: Long COVID, characterized by a persistent symptom spectrum following SARS-CoV-2 infection, poses significant health, social, and economic challenges. This review aims to consolidate knowledge on its epidemiology, clinical features, and underlying mechanisms to guide global responses; Methods: We conducted a systematic literature review, analyzing peer-reviewed articles and reports to gather comprehensive data on long COVID’s epidemiology, symptomatology, and management approaches; Results: Our analysis revealed a wide array of long COVID symptoms and risk factors, with notable demographic variability. The current understanding of its pathophysiology suggests a multifactorial origin yet remains partially understood. Emerging diagnostic criteria and potential therapeutic strategies were identified, highlighting advancements in long COVID management.; Conclusion: This review highlights the multifaceted nature of long COVID, revealing a broad spectrum of symptoms, diverse risk factors, and the complex interplay of physiological mechanisms underpinning the condition. Long COVID symptoms and disorders will continue to weigh on healthcare systems in years to come. Ad-dressing long COVID requires a holistic management strategy that integrates clinical care, social support, and policy initiatives. The findings underscore the need for increased international cooperation in research and health planning to address the complex challenges of long COVID. There is a call for continued refinement of diagnostic and treatment modalities, emphasizing a multidisciplinary approach to manage the ongoing and evolving impacts of the condition.

The basic oxygen furnace slag (BOF) was wide used in road construction, but there was a lack of characteristics in different asphalt mixtures. This study investigates the properties of hot-mixed asphalt (HMA) containing stone mastic asphalt (SMA), porous asphalt (PA) and dense-graded BOF as a partial substitution for natural aggregates. The purpose of this study is to evaluate various BOF slag contents in the asphalt mixtures would affect the cooling behavior after compaction. Asphalt mixture specimens contained 0%, 20%, 40% and 60% BOF slag, respectively, as coarse aggregate. Test results showed that BOF slag has a lipophilic property, so it can be adsorbed by asphalt cement, thereby reducing the cost of asphalt. The stability value of all asphalt mixtures increases with the proportion of BOF slag replacement. In addition, the voids in the mineral aggregate (VMA) value variable exhibited significant differences among asphalt mixtures, and could determine the deviation of the cooling trend of asphalt mixtures. Furthermore; it was found that the cooling procedure of the BOF slag used in dense-graded asphalt mixture takes about 100 min, and that the temperature tends to be moderate; however, it took about 120 min of cooling the SMA and PA mixture with BOF slag. In addition, the voids distribution of dense asphalt mixture was not uniform. It would result in various locations of thermal energy temperature on asphalt mixtures that were inconsistent.

The control of the fine particle emission from the coal-fired power plants has been a big challenge in china. Either the conventional electrostatic precipitator or the fabric filter has some shortages. The electrostatic precipitator is hard to keep high efficiency for the submicron particles. The fabric filter could keep high efficiency but with very high pressure drop. One solution is to combine them together. Several types of hybrid particle collectors (HPC) combining the electrostatic precipitator and the fabric filter together have been developed and applied in a number of projects in China. In recent years, numerical simulation technology has been widely used in the design of the collectors. In this paper, an unsteady numerical model is used to investigate the particle deposition characteristics in a scale hybrid collector. The fluid field is modeled by using incompressible Navier-Stokes equations with the RNG turbulence equations. The corona discharge is solved by using a finite volume method. The particle charging is modeled by using a filed-diffusing combined model. And an unsteady cake formation model is used to simulate the filtration process.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

The Atmospheric Dynamics Mission ADM-Aeolus was successfully launched in August 2018 by the European Space Agency (ESA). The Aeolus mission carried a single instrument, the first-ever Doppler Wind Lidar (DWL) in space, called Atmospheric LAser Doppler INstrument (ALADIN). Aeolus circled the Earth in a polar sun-synchronous orbit at about 320 km altitude with a repeat cycle of 7 days, providing vertical profiles of horizontal line-of-sight (HLOS) winds on a global scale. Exceeding scientific expectations, Aeolus, initially designed for a 3-year lifetime, provided global coverage of wind profiles for almost five years. In this long-term validation study, we assessed the accuracy of the Level 2B (L2B) Rayleigh-clear and Mie-cloudy wind products by collecting radiosonde data from three stations in the Brazilian Amazon: Cruzeiro do Sul (7.62° S, 72.67° W), Porto Velho (8.76° S, 63.91° W), and Rio Branco (10.00° S, 67.80° W). Statistical validation was conducted by comparing Aeolus L2B wind products and radiosonde data, launched daily at 12:00 UTC from October 2018 to March 2023. Considering all data collected during the mission period, Pearson’s coefficient (R) of 0.73 was observed in Rayleigh-clear and 0.85 in Mie-cloudy, revealing a strong correlation between Aeolus and radiosonde winds. No significant biases were detected, with values of -0.14 m/s for Rayleigh-clear and -0.40 m/s for Mie-cloud, fulfilling the mission requirement of having absolute biases below 0.7 m/s. However, when analyzed annually, in 2022, the bias for Rayleigh-clear was -0.95 m/s, exceeding the mission requirements.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Long Covid is a debilitating condition that has been well-documented over the past 4 years and shares many similarities with other post-viral chronic illnesses. Despite this, clinicians are not confident in recognising the signs of Long Covid, or effectively managing the symptoms of their patients. This paper presents a single patient case report from a biomedical researcher who has had Long Covid for 2 years; it is written in relatively plain language to be accessible to both patients and clinicians across multiple specialities. The author has had the ability and expertise to keep up with the Long Covid research literature, and from that has cobbled together a management strategy that has alleviated her own symptoms, and those of other people with whom she has shared her protocol. The author’s experience of developing and managing her Long Covid is presented here, in the hopes that it may be of assistance to clinicians in identifying and managing Long Covid in their own patients.

Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host and the possible outcomes of host-pathogen interaction.

The intricate mechanisms of the immune response elicited by vaccines and the interplay between the immune system and the central nervous system (CNS) are poorly understood. This review explores these mechanisms, emphasizing the interplay between the immune system and the central nervous system (CNS). A critical aspect is the examination of how vaccine-induced immune responses can interact with the CNS, influencing neuroinflammation and neuroimmune interactions. Furthermore, the link between vaccination and persistent symptoms observed in long-COVID patients is discussed. Vaccination initiates a complex cascade of events, starting with the production of specific proteins, such as S1/S2 spike proteins, leading to robust immune activation in the axillary lymph nodes. The role of macrophages and antigen-presenting cells (APCs) in cytokine production, antigen presentation, and the stimulation of B and T cells highlights the sophistication of the adaptive immune response. The migration of immune cell-derived exosomes to the brain plays a dynamic role in CNS inflammation, neurodegenerative processes and long COVID. On the other hand, the prolonged presence of viral and vaccine-derived spike proteins may contribute to the complex pathophysiology of Long-COVID, shedding light on the delicate balance between beneficial immune responses and possible adverse neurological outcomes of vaccination. It is worth rigorous monitoring and further research to understand the mechanisms of neuroinflammation and the persistence of spike proteins and their long-term effects on the brain, emphasising the importance of a nuanced approach to vaccine safety and efficacy in the context of COVID-19 and beyond.Principio del formulario

Long COVID–19 syndrome is another vicious feature of COVID-19 infection, the mechanism remains unidentified. Several observational studies suggest that vaccinations might have protective and therapeutic effect on long COVID-19 and our study aimed to assess the influence of vaccination on COVID-19 patients. We performed an observational cohort study from October 2020 to July 2022, which included 503 patients (291 males and 212 females) with a median age of 65. They were hospitalized due to COVID-19 pneumonia and had persistent symptoms (after 1 month of COVID-19 infection. The clinical and demographic data including vaccination status collected during hospitalization and regular visits at the Community Healthcare Center dr. Adolf Drolc Maribor were analyzed. More non-vaccinated patients acquired long COVID-19 than vaccinated. Patients with type 2 diabetes suffered from long COVID-19 in a smaller percentage than patients without diabetes. Gender, inhalational therapy due to chronic pulmonary disease and the number of complications have significantly influenced long COVID-19 development and the mostly vaccinated patients were older and with asthma/COPD. Our study confirmed that vaccination is a safe and effective measure to prevent the severe progression of acute disease and to lower the incidence of developing long COVID.

Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (r_s 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.

The paper presents the prediction of hydrodynamic characteristics of different rudder -plane configurations behind a submarine in deep water through the Reynolds-Averaged Navier-Stokes method in Ansys Fluent Solver. The hydrodynamic force and moment acting on the Cross-plane, X-plane, and Y-plane rudder configurations are analyzed for estimating hydrodynamic coefficientsfor predicting the advantages of each configuration to control the ship. The obtained results show that X-force of the X-plane rudder configuration is larger than the force acting on the Cross-plane rudder and Y-plane rudder configurations. However, Y-force, and Z-force of the X-plane rudder configuration are significantly greater than the Y-force of the left configurations. The same tendency can be seen in the moment of the X-plane rudder about the y-axis and z-axis. The roll moment induced by the Y-plane and Cross-plane rudder configurations is significantly larger than the case of the X-plane rudder configuration.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

Dinoflagellates are one of the largest groups of marine microalgae and exhibit diverse trophic strategies. Within these niches, dinoflagellates can produce secondary metabolites that are known to be toxic, which can lead to ecologically harmful blooms. Amphidinium carterae is one species of dinoflagellate that produces toxic compounds and is used as a model for dinoflagellate studies. The extent to which the microbiome surrounding A. carterae affects its growth and secondary metabolite synthesis is still being assessed, as well as the impact of bacterial data on sequencing and assembly. An antibiotic cocktail was previously shown to eliminate 16S amplification from the dinoflagellate culture. Even with drastically reduced bacterial numbers, bacterial populations are likely to be present. In this experiment we used novel Nanopore long-read sequencing techniques on A. carterae cultures to assemble 15 full bacterial genomes ranging from 2.9-6.0 Mb and found that the use of antibiotics decreased the percentage of reads mapping back to bacteria. We also identified shifts in the microbiome composition and identified a potentially deleterious bacterial species arising in the absence of the antibiotic-treatment. Multiple antibiotic-resistance genes were identified, as well as evidence that the bacterial population do not contribute to toxic secondary metabolite synthesis.

This study uses machine learning to identify key factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) from user ratings and prices, we analyzed data from Amazon. The findings indicate that FSA/HSA eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were found to be cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

Pruning is one of the most important tree fruit production activities, which is highly dependent on human labor. Skilled labor is in short supply, and the increasing cost of labor is becoming a big issue for the tree fruit industry. Growers are motivated to seek mechanical or robotic solutions for reducing the amount of hand labor required for pruning. This paper reviews the research and development of sensing and automated systems for branch pruning for tree fruit production. Horticultural advancements, pruning strategies, 3D structure reconstruction of tree branches, as well as practice mechanisms or robotics are some of the developments that need to be addressed for an effective tree branch pruning system. Our study summarizes the potential opportunities for automatic pruning with machine-friendly modern tree architectures, previous studies on sensor development, and efforts to develop and deploy mechanical/robotic systems for automated branch pruning. We also describe two examples of qualified pruning strategies that could potentially simplify the automated pruning decision and pruning end-effector design. Finally, the limitations of current pruning technologies and other challenges for automated branch pruning are described, and possible solutions are discussed.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID. We describe the molecular mechanisms underlying virus-host interactions, including alterations in protein expression, intracellular signaling pathways, and immune responses. In particular, the article highlights the potential impact of these cytopathies on cellular function and clinical outcomes, such as immune dysregulation, neuropsychiatric disorders, and organ damage. The article concludes by discussing future directions for research and implications for the management and treatment of COVID-19 and Long-COVID.

The COVID-19 pandemic has led to a substantial revolution in the incorporation of digital solutions in healthcare. This systematic review investigates the enduring physical and psychological consequences individuals experience up to two years post-recovery. Additionally, it focuses on examining the influence of mHealth interventions on these effects. Significantly, 41.7% of survivors experience lingering symptoms that have not been addressed, while 14.1% encounter difficulties in returning to work. The presence of anxiety, compromised respiratory functioning, and persistent symptoms highlight the immediate requirement for specific therapies. Telehealth, particularly telerehabilitation, presents itself as a possible way to address these difficulties. The study thoroughly examines 10 studies encompassing 749 COVID-19 patients, investigating the efficacy of telerehabilitation therapies in addressing various health markers. Telerehabilitation-based breathing exercises yield substantial enhancements in functional performance, dyspnea, and overall well-being. The results emphasize the potential of telerehabilitation to have a favorable effect on patient outcomes, however more research is needed to strengthen the existing evidence basis as one of the most important limitation is the limited number of trials and the evaluation of varied therapies. The analysis highlights the significance of digital solutions in post-COVID care and calls for ongoing research to improve comprehension and implementation of telehealth interventions in a swiftly changing healthcare environment.

Since the outbreak of COVID-19, social media platforms, such as Twitter, have experienced a tremendous increase in conversations related to Long COVID. The term “Long COVID” describes the persistence of symptoms of COVID-19 for several weeks or even months following the initial infection. Recent works in this field have focused on sentiment analysis of Tweets related to COVID-19 to unveil the multifaceted spectrum of emotions, viewpoints, and perspectives held by the Twitter community. However, most of these works did not focus on Long COVID, and the few works that focused on Long COVID have limitations. Furthermore, no prior work in this field has investigated Tweets where individuals self-reported experiencing Long COVID on Twitter. The work presented in this paper aims to address these research challenges by presenting multiple novel findings from a comprehensive analysis of a dataset comprising 1,244,051 Tweets about Long COVID, posted on Twitter between May 25, 2020, and January 31, 2023. First, the analysis shows that the average number of Tweets per month where individuals self-reported Long COVID on Twitter, has been considerably high in 2022 as compared to the average number of Tweets per month in 2021. Second, findings of sentiment analysis using VADER show that the percentage of Tweets with positive, negative, and neutral sentiment were 43.12%, 42.65%, and 14.22%, respectively. Third, the analysis of sentiments associated with these Tweets also shows that the emotion of sadness was expressed in most of these Tweets. It was followed by the emotions of fear, neutral, surprise, anger, joy, and disgust, respectively.

As the name implies, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-stranded RNA virus and a member of the corona virus family, primarily affecting the upper respiratory system and the lungs. Like many other respiratory viruses, SARS-CoV-2 can spread to other organ systems. Apart from causing diarrhea, another most common but debilitating complication caused by the SARS-CoV-2 is neurological symptoms and cognitive difficulties, which occur in up to two thirds of hospitalized covid patients and ranging from shortness of concentration, overall declined cognitive speed to executive or memory function impairment. Neuro-cognitive dysfunction and “brain fog” are frequently present in COVID-19 cases, which can last several months after the infection, leading to disruption of daily life. Cumulative evidence suggests that SARS-CoV-2 affects vasculature in the extra pulmonary systems directly or indirectly, leading to impairment of endothelial function and even multi-organ damage. The post COVID-19 long-lasting neurocognitive impairments have not been studied fully; and the underlying mechanism remains elusive. In this review, we summarize the current understanding of the effects of COVID-19 on vascular dysfunction and how vascular dysfunction leads to cognitive impairment in patients.

The coronavirus disease 2019 (COVID-19), instigated by the zoonotic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), rapidly transformed from an outbreak in Wuhan, China, into a widespread global pandemic. A significant post-infection condition, known as ‘long- COVID’, emerges in a substantial subset of patients, manifesting with a constellation of over 200 reported symptoms that span multiple organ systems. This condition, also known as 'post-acute sequelae of SARS-CoV-2 infection' (PASC), presents a perplexing clinical picture with far-reaching implications, often persisting long after the acute phase. While initial research focused on the immediate pulmonary impact of the virus, the recognition of COVID-19 as a multiorgan disruptor has unveiled a gamut of protracted and severe health issues. This review provides a summary of the primary effects of long COVID on the cardiovascular, nervous, and respiratory systems. It also delves into the mechanisms underlying these impacts and underscores the critical need for a comprehensive understanding of long COVID's pathogenesis.

Background: COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being described. Objective: To describe the findings of a current systematic review of the long-term effects related to post-COVID-19 sequelae. Design: A systematic review was carried out in which cohort studies, case series, clinical case reports were included, and the PubMed, Scielo, SCOPUS and Web of Science databases were ex-tracted. Information published 2020 to June 1, 2022, was sought. Results: We reviewed 300 manuscripts during the first step of the literature review process. Then 260 abstracts were analyzed. In the end, we included 32 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 9 for neurological and psychiatric, and 8 for cutaneous sequelae. Conclusion: Studies show that the most common sequelae are those linked to the lungs, followed by skin, cutaneous and psychiatric alterations. Women report a higher incidence of the sequelae, as well as those with comorbidities and severer COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its apparition but has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems and further burden healthcare systems around the world.

The COVID-19 pandemic has had a significant impact on every individual in the United States. The launch of the COVID-19 vaccines is estimated to have averted millions of deaths and reduced over 18 million COVID-19 related hospitalizations. In September 2023, the updated 2023-2024 COVID-19 vaccine that include a monovalent component that corresponding to the omicron variant XBB.1.5 reflecting the predominant circulating variant at the time of strain selection, was approved and was recommended for use in all people ≥ 6 months of age. Despite this recommendation, the US uptake of the updated COVID vaccines over the 2023-2024 season has been far from optimal, placing many people at unnecessary risk of severe COVID-19 outcomes. This paper provides an overview of the current state of COVID-19 in 2023-2024, and barriers to vaccine uptake. With the continued evolution of the virus, the potential for more virulent variants and the lower public acceptance of vaccination, the potential barriers that contributed to low vaccine uptake are explored, as well as to provide solutions for improving COVID-19 protection for future seasons.

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state of the art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states which interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological sates, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented adding an exponential cutoff to the interaction term of PPP model. In this way, an adjusted cutoff distance λ = 2 allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond Hubbard model but not completely unscreened as is the case for the PPP model.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder characterized by cognitive decline and neuronal loss, representing a most challenging health issue. We present a computational analysis of transcriptomic data of AD tissues vs. healthy controls, focused on elucidation of functional roles played by long non-coding RNAs (lncRNAs) throughout the AD progression. We first assembled our own lncRNA transcripts from the raw RNA-Seq data generated from 527 samples of dorsolateral prefrontal cortex, resulting in the identification of 31,574 novel lncRNA genes. Based on co-expression analyses between mRNAs and lncRNAs, a co-expression network is constructed. Maximal subnetworks with dense connections are identified as functional clusters. Pathway enrichment analyses are conducted over mRNAs and lncRNAs in each cluster, which serve as the basis for the inference of functional roles played by lncRNAs involved in each of the key steps in an AD development model that we have previously build based on transcriptomic data of protein-encoding genes. Detailed information is presented about the functional roles by lncRNAs in activities related to stress response, reprogrammed metabolism, cell-polarity, and development. Our analyses have also revealed that lncRNAs have discerning power in distinguishing between AD samples of each stage and healthy controls. This study represents the first of its kind.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

The ongoing COVID-19 pandemic has profoundly affected millions of lives globally, with some individuals experiencing persistent symptoms even after recovering. Understanding and managing the long-term sequelae of COVID-19 is crucial for research, prevention, and control. As a result, to monitor the health of individuals affected by these conditions, they must maintain up-to-date health records using digital health informatics apps for surveillance. In this review, we provide an overview of the existing literature on identifying long COVID manifestations through hierarchical classification and the characterization of long COVID by different hierarchical groups based on the Human Phenotype Ontology (HPO). We outline the aspects of the National COVID Cohort Collaborative (N3C) and Researching COVID to Enhance Recovery (RECOVER) in artificial intelligence (AI) to identify long COVID. Knowledge exploration, using the concept map for the clinical pathways of long COVID presented in this paper, provides an overview of the data needed to explore tackling the long-term effect of COVID-19 by integrating innovative cohesive frameworks and designing health informatics-based applications. To the best of our knowledge, this is the first paper to explore the potential incorporation of long COVID as a variable risk factor within a digital health informatics application.

Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms generally referred as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children's Sleep Habits Questionnaire (CSHQ-DE). We compared sleep behavior at three different time points: pre-COVID-19, post-COVID-19 at initial presentation and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range 0-18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients, whilst 11% experienced moderate disease. Initial presentation occurred at a median of 20.4 weeks (6 weeks - 14 months) after infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82+8.7 points) to post-COVID-19 (49.40+8.3 points; p=&lt;0.01). The score then normalized at re-presentation (46.98+7.8; p=0.1). The greatest changes were seen in the CSHQ-DE subscale score "daytime sleepiness". Our data show that children and adolescents with long COVID often suffer from sleep disturbance. For most children and adolescents these sleep disorders decreased over time without further medical intervention, aside from a basic sleep consultation.

In all forms of folk beliefs, ancestor worship is a universal traditional belief form of the Vietnamese people. As a Vietnamese people, “everyone worships their ancestors, everyone worships their parents and grandparent”. Ancestor worship is a common belief in the whole country. It is a belief that expresses the deeply humanistic spirit of the Vietnamese people and has great values in human life. So, what is the nature of ancestor worship? What is the values of ancestor worship in life? And in the context of globalization, how has this the belief changed? This study focuses on analyzing the above contents, thereby highlighting the value of this belief in the spiritual life of Vietnamese people; to point out the positive and negative changes of this belief in the current period; from that, take the right measures to bring into play the positive and limit the negative side of those changes in the spiritual life of Vietnamese people.

Both in lung adenocarcinoma (LUAD) and severe acute respiratory syndromes (SARS) uncontrolled inflammation could be detected in lung tissue. Whether the similarity mechanism exists is still unknown. PDZ-binding motif (PBM) in SARS-CoV E protein has been demonstrated as virulence factor induce inflammation storm. Study function of PBM in LUAD is significant for mechanism exploration of carcinogenesis mediated by SARS-CoV. To identify gene expression fluctuation induced by PBM, a microarray sequencing data of lung tissue infected by wild type (SARS-CoV-E-wt) and recombinant virus (SARS-CoV-E-mutPBM) was analysis followed by functional enrichment analysis. To understand the role of screened specific genes in LUAD, overall survival and immune correlation were calculated. A total of 12 genes (MAPK1, PRKCA, FGFR4, KDR, PTPRD, BCL2L15, UBD, MAMDC2, LTBP4, PTPRB, LGI3 and ITGA8) might participate in initial and development stage of LUAD through expression variation and mutation. Meanwhile, a total of 12 genes (CARHSP1, EIF4E2, HMGA1, IL1R2, MAGOHB, PVR, ADCY9, ELF5, ESYT3, SCML4, SECL14L4 and THRA) could lead to poorer prognosis via dysregulation. In addition, MAMDC2 and ITGA8 down-regulated by PBM could also alter prognosis. Though the conservative PBM (-D-L-L-V-) could be found at the end of carboxyl terminal in multi E proteins of coronaviruses, the specific function of each one depend on the whole amino acid sequence simultaneously. In conclusion, PBM of SARS-CoV E protein could promote carcinogenesis of LUAD by dysregulating important gene expression profiles followed by influence immune response and overall prognosis. The results in present study also provided reference for the therapy of SARS-CoV-2 in LUAD patients.

Background: The validation of laser usage during laparoscopic procedures, notably by Camran Nezhat in the late 1980s, has been significant. Lasers offer precision and depth control in tissue vaporization without bleeding. Surgical intervention remains central in managing endometrio-sis-associated pain and infertility, especially for patients unresponsive to hormonal therapy. Methods: This retrospective cohort study included 200 patients with SPE who underwent laparo-scopic laser vaporization. Surgery was performed using a CO2 laser, and histological confirma-tion of endometriosis was obtained for all cases. Pain scores and SF-36 questionnaire domains were assessed preoperatively and postoperatively. Fertility outcomes were evaluated among pa-tients desiring pregnancy. Results: Significant improvements in pain score and SF-36 questionnaire domains were ob-served postoperatively (p-value

Mutations of PKD1 coding for polycystin-1 (PC1) account for most of the autosomal dominant polycystic kidney disease (ADPKD). The extracellular region of PC1 contains many evolutionarily conserved domains for ligand interactions. Among these is the leucine-rich repeats (LRR) in the far N-terminus of PC1. Using zebrafish (Danio rerio) as an in vivo model system, we explored the role of LRR in the function of PC1. Zebrafish expresses two human PKD1 paralogs, pkd1a and pkd1b. Knockdown of both genes in zebrafish by morpholino antisense oligonucleotides produced phenotypes of dorsal axis curvature and pronephric cyst formation. We found that overexpression of LRR suppressed both phenotypes in pkd1-morphant zebrafish. Purified recombinant LRR domain inhibited proliferation of HEK cells in culture and interacted with the heterotrimeric basement membrane protein laminin-511 (α5β1γ1) in vitro. Mutations of amino acid residues in LRR structurally predicted to bind laminin-511 disrupted LRR-laminin interaction in vitro and neutralized the ability of LRR to inhibit cell proliferation and cystogenesis. Our data support the hypothesis that the extracellular region of PC1 plays a role in modulating PC1 interaction with the extracellular matrix and contributes to cystogenesis of PC1-deficiency.

Long-term safety of a nutraceutical combination based on agnus castus and magnolia extracts combined with soy isoflavones (SI) and lactobacilli, and effectiveness on vasomotor symptoms and sleep disorders in postmenopausal women, were assessed. A controlled study was carried-out in menopausal women comparing this nutraceutical combination (ESP group) with formulation containing isoflavones alone (C group), at the dosage recommended. Kuppermann index, PSQI, and SF-36 were determined at baseline, 3, 6 and 12 months. Endometrial thickness, mammary density and liver function were evaluated at baseline and after 12 months. 180 women (100 in ESP group and 80 in C group, mean age 55.5 years, in menopause for about 36 months) were enrolled in the study. At the treatment end, mammary density, endometrial thickness, and hepatic function did not show substantial differences between groups. Kuppermann index, and particularly hot flushes, were progressively and significantly decreased in frequency and severity during ESP versus C treatment. No adverse events were observed. Agnus castus and magnolia, combined with SI + lactobacilli, can effectively and safely be used in symptomatic postmenopausal women, mainly when quality of sleep is the most disturbing complaint. Endometrium, mammary glands and liver function, were unaffected after 12 months treatment.

In many European countries over the last decades, arable fields dominate agriculture landscapes, leading to a very intensive land-use practices. This reason seems to be the main cause of popula-tions declines for numerous farmland species, including the European hare (Lepus europaeus Pallas, 1778). The Research institute for Animal Production (National Agricultural and Food Centre, Luzianky, Slovakia) has been engaged in a long monitoring project (project currently run-ning), collecting certain indicators of hare population dynamics during hunting season since 1987 to 2023 in the Slovak Danubian Lowland. In the same macro-area (Čiližská Radvaň and Lehnice) a study was conducted on the influence of permanent semi-natural vegetation in relation to re-cruitment, population density and production. The whole monitored period was aggregated into 5-years intervals (for a total of 7 time-intervals), with the aim of analyzing the brown hare popu-lation dynamics. Spring hare density in the Danubian Lowland is currently 20.8 hares/km2, with harvests of 4.6 hares/km2. During all the monitoring period, bag’s animals have been examined following the regular hunting operations for the purpose of age determination (weight of eye lenses), sex ratio and productivity. The results of our analysis showed that the proportion of juve-nile in bag (PYB) among those shot varied from 37.0 % of the last 5-years interval (2018-2023), to a maximum of 51.0 % in interval of years 1998-2002. On total average there were 1.86 juveniles per adult female (r). The proportion of adult females in gamebag varied from 22.58 % (years in-terval 1992-1997) to 31.26 % (years interval 2018-2023). Sex-ratio (SI; males : females) among shot hares showed a value of 0.50, ranged from 0.48 in the period 2008-2012 to 0.52 in the first observed period (years 1987-1991) and in the last one (years 2018-2023). Average weight of shot hares was 4.04 kg (juveniles 3.83 kg, adults 4.27 kg, adult males 4.21 kg and females 4.32 kg). There was a large positive effect of set-aside with special mixtures, created for hares in large-scale farmed agrarian landscape, on hare density, bag and recruitment. In model hunting grounds with such set-asides increased the spring stock by 25 %, bag by 100 % and recruitment by 20 %. This study reveals that the management of European brown hare is not sustainable, and the population is decreasing. It is proved through the decline of harvest hares and by population dynamics parameters. Environmental improvements lead to the stabilization and increasing of requested parameters.

Recently, the awareness of energy conservation, carbon emission reduction, and environmental protection in Taiwan has begun to gradually improve, and bicycles have become an important vehicle for residents. In 2009, Kaohsiung began promoting public bicycle sharing. The number of users in that year amounted to 140,000. By 2015, the accumulated number of users reached nine million. This study adopted the Theory of Planned Behavior (TPB) to explore the factors influencing the behavioral intentions of public bicycle users, including the three dimensions of attitude, subjective norm, and perceived behavioral control, and probed into the relationship between the factors influencing the behavioral intentions of public bicycle users in Kaohsiung City and the dimensions. This study used a questionnaire to collect data and SPSS & AMOS for statistical analysis. The empirical results demonstrated that the most prominent factors influencing the behavioral intentions of public bicycle users in Kaohsiung City included perceived behavioral control, attitude, and subjective norm, in order. Among the influencing factors in the three dimensions, personal interests, main groups, and self-competence had a positive and significant correlation. Administrators should provide more incentives related to the three influencing factors to encourage the public in Kaohsiung City to use public bicycles more frequently as their short-distance travel mode, so as to achieve the purposes of saving energy, reducing carbon emissions, and protecting the urban environment.

Most of the mid-high permeability sandstone oilfields in China have entered the ultra-high water cut stage, accompanied with the highly-dispersed residual oil, and the control effect of mi-cro-heterogeneity on the residual oil is increasingly prominent. Understanding the microscopic characteristics of pore structural and its evolution during the long-term waterflooding is critical for enhancing the accuracy and efficiency of oil field exploitation. While the previous insights paid more attention to the geometrical and morphological features of pore structure and ignores the relation of pore structure with the fluid flow capacity. In this study, we propose a microscopic pore structure classification method considering pore size and local permeable capacity, which realizes the physical classification and quantitative evaluation of pore structure characteristics for different permeability rocks. The micro-pore structure is classified into 6 types based on the key evaluation parameters of pore diameter and flow flux area. By taking six mid-high permea-bility sandstone core samples from Daqing oilfield in China, a series of long-term waterflooding experiments are carried out and the interior pore structure was captured using high precision CT scanning technique. The results reveals that high-permeability reservoirs exhibit concentrated pores diameters and finer throats, whereas mid-permeability reservoirs exhibit smaller pores and throats in greater quantity. With the increase of water injection volumes, the permeable ca-pacity and connectivity of the high-connectivity pore space in ultra-high- and high-permeability reservoirs are enhanced, and in mid-permeability reservoirs, the micro-heterogeneity intensifies the increase in low-connectivity small pores. These findings provide new insights for the micro-scopic heterogeneity and a solid theoretical basis for investigating the occurrence of microscopic residual oil and optimising enhanced oil recovery strategies at the late stage of ultra-high water cut.

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS) and Long COVID are characterized by debilitating post-exertional malaise and other core symptoms related to immune dysregulation resultant from post-viral infection, including mitochondrial dysfunction, chronic neuroinflammation and gut dysbiosis. The reported associations between altered microbiota composition and cardinal symptoms of ME/CFS and Long COVID, suggesting that use of microbial preparations, such as probiotics, by restoring the homeostasis of the brain-immune-gut axis may help in the management of symptoms in both conditions. Therefore, this review aims to investigate the implications of alerted gut microbiome and assess the evidence supporting use of microbial-based preparations, including probiotics, synbiotics, postbiotics alone and/or in combination with other nutraceuticals in the management of fatigue, inflammation, as well as neuropsychiatric and gastrointestinal symptoms among patients with ME/CFS and Long COVID.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. SARS-CoV-2 nucleic acid, peripheral lymphocyte count, and functionality were assessed. SARS-CoV-2-specific and neutralization antibodies were detected, followed by virus isolation and genome sequencing. The median age of the studied cohort was 59.83±12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. Interferon gamma (IFN-ƴ)-generated CD4+ and CD8+ cells were normal as 24.68±9.60% and 66.41±14.87%. However, the number of IFN-ƴ-generated NK cells diminished (58.03±11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (ID50=157.2, P=0.05). SARS-CoV-2 was not isolated, and a cytopathic effect was lacking. Only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity was observed in COVID-19 patients with long-term SARS-CoV-2 infection.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

YOLOv8, as an efficient object detection method, can swiftly and precisely identify objects within images. However, traditional algorithms encounter difficulties when detecting small targets in remote sensing images, such as missing information, background noise, and interactions among multiple objects in complex scenes, which may affect performance. To tackle these challenges, we propose an enhanced algorithm optimized for detecting small objects in remote sensing images, named HP-YOLOv8. Firstly, we design the C2f-D-Mixer (C2f-DM) module as a replacement for the original C2f module. This module integrates both local and global information, significantly improving the ability to detect features of small objects. Secondly, we introduce a feature fusion technique based on attention mechanisms, named Bi-Level Routing Attention in Gated Feature Pyramid Network (BGFPN). This technique utilizes an efficient feature aggregation network and reparameterization technology to optimize information interaction between different scale feature maps, and through the Bi-level Routing Attention (BRA) mechanism, it effectively captures critical feature information of small target objects. Finally, we propose the Smooth Mean Perpendicular Distance Intersection over Union (SMPDIoU) loss function. The method comprehensively considers the shape and size of detection boxes, enhances the model's focus on the attributes of detection boxes and provides a more accurate bounding box regression loss calculation method. To demonstrate our approach's efficacy, we conduct comprehensive experiments across the RSOD, NWPU VHR-10, and VisDrone2019 datasets. The experimental results show that the HP-YOLOv8 achieves 95.11%, 93.05%, and 53.49% in the [email protected] metric, and 72.03%, 65.37%, and 38.91% in the more stringent [email protected]:0.95 metric, respectively.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and communication, anxiety, hyperactivity, and restricted interest for specific subjects. In addition to the genetic factors, multiple environmental factors have been related to the development of ASD. Animal models can serve as crucial tools for understanding the complexity of ASD and identifying potential therapeutic strategies. In this study, a chemical model of ASD has been developed in zebrafish by exposing embryos to valproic acid (VPA) from 4 to 48 hours post-fertilization. After the exposure, embryos were transferred to fish water and the effects on behavior and neurotransmitters profile were analyzed at both larval and adult stages. Larvae from VPA-treated embryos showed hyperactivity and decreased visual and vibrational escape responses, as well as an altered neurotransmitters profile, with increased glutamate and decreased acetylcholine and norepinephrine levels. Adults from VPA-treated embryos exhibited impaired social behavior characterized by larger shoal sizes and a decreased interest for their conspecifics. Neurotransmitter analysis revealed a significant decrease in dopamine and GABA levels in the brain. These results support the interest of this model in the study of ASD.

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.

Static standing postural stability has been measured by multiscale entropy (MSE), which is used to measure complexity. In this study, we used the average entropy (AE) to measure the static standing postural stability, as AE is a good measure of disorder. The center of pressure (COP) trajectories were collected from 11 subjects under four kinds of balance situation, from stable to unstable: bipedal with open eyes, bipedal with closed eyes, unipedal with open eyes, and unipedal with closed eyes. The AE, entropy of entropy (EoE), and MSE methods were used to analyze these COP data, and EoE was found to be a good measure of complexity. The AE of the 11 subjects sequentially increased by 100%as the balance situations progressed from stable to unstable, but the results of EoE and MSE did not follow this trend. Therefore, AE, rather than EoE or MSE, is a good measure of static standing postural stability. Furthermore, the comparison of EoE and AE plots exhibited an inverted U curve, which is another example of a complexity versus disorder inverted U curve.

In this tutorial review, we compare and contrast the chemical mechanisms of electrophile/oxidant sensing, and the molecular mechanisms of signal propagation. We critically analyze biological systems in which these different pathways are believed to be manifest and what the data really mean. Finally, we discuss applications of this knowledge to disease treatment and drug development.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.

As the application of cyber-physical systems (CPSs) becomes more and more widespread, its security is becoming a focus of attention. Currently, there has been much research on the security defense of the physical layer of the CPS. However, most of the research only focuses on one of the aspects, for example, attack detection, security state estimation or recovery control. Obviously, the effectiveness of security defense targeting only one aspect is limited. Therefore, in this paper, a set of security defense processes is proposed for the case that a CPS containing multiple sensors is subject to three kinds of stealthy attacks (i.e., zero-dynamics attack, covert attack, and replay attack). Firstly, the existing attack detection method based on improved residuals is used to detect stealthy attacks. Secondly, based on the detection results, an optimal state estimation method based on improved Kalman filtering is proposed to estimate the actual state of the system. Then, based on the optimal state, internal model control (IMC) is introduced to complete the recovery control of the system. Finally, the proposed methods are integrated to give a complete security defense process, and the simulation is verified for three kinds of stealthy attacks. The simulation results show that the proposed methods are effective.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

Li₂MnO₃ is critical component in the well-studied Li-excess cathode materials xLi₂MnO₃•(1- x)LiMO₂ for achieving high lithium storage capacity. In this article, the diffusion of Li ions in Li₂MnO₃ is studied using molecular dynamics (MD) simulation with well-behaved empirical force fields obtained by fitting against the crystal structure from experiment and phonons calculated using Density Function Theory (DFT). We have found two possible tetrahedral hopping channels, 0-TM and 1-TM(Mn⁴⁺) channel, which are differentiated by the face sharing octahedral cations. Simulation results show that the 0-TM channel is active for Li hopping, while 1-TM(Mn4+) channel is inactive. During the delithiation process, the Li ions in the TM layered are firstly removed, then those in the Li layer. However, the Li ions will be trapped in the tetrahedral 0-TM channels as long as the four face sharing octahedral sites are cleared. Up to x=1.0 for Li₂-xMnO₃, almost all the Li ions are located at the tetrahedral sites, forming a regular array along a axis. The de-intercalation of tetrahedral Li ions requires a high voltage (>5.2 V vs. Li/Li+), limiting the practical capacities measured in lab. The diffusion of Mn ions into the Li layers is observed in a deeper delithiated structure (x=1.2 for Li₂-xMnO₃), indicating an initial phase transformation to a spinel-like structure. However, the Mn ions are mainly trapped in the tetrahedral sites in the Li layer, instead of the octahedral sites fin spinel-like structure. A few of Mn ions diffusing into the octahedral sites in Li layers have no face sharing tetrahedral Li ions, revealing a further Li de-intercalation is imperative for the complete phase transformation. Our model is not stable for x≥1.4 in Li₂-xMnO₃. Other charge compensation mechanism should be considered in this high delithiation stage, eg. oxygen release.

The knowledge of COVID-19 impact on the human body has increased rapidly. Although many people recover from COVID-19, some continue to experience persistent symptoms that have been identified as Long COVID. This condition can have a severe impact on quality of life, and it remains a significant concern for medical professionals and researchers. One of the key components of the SARS-CoV-2 virus that enables it to enter human cells is the spike (S) protein. Recent studies have revealed a complex network of interactions between G proteins, spike (S) protein, and the Renin-Angiotensin System (RAS) may be responsible, at least in part, for long COVID. SARS-CoV-2 can also affect the brain, leading to neurological symptoms such as confusion, memory loss, and fatigue. Increasing evidence suggests that COVID-19 is not just a respiratory illness since it is likely that the virus could influence signal transduction pathways such as G-protein-coupled receptor (GPCR), among others, in the brain, either directly or indirectly, affecting neural functions. These interactions with the spike (S) protein and RAS, alongside the brain, are complex and require deep research to understand their implications for Long COVID-19 manifestation fully. While recent research has shed light on the complex interactions between G proteins, spike (S) protein, the brain, and the angiotensin system, this article explores these interconnected pathways and their implications for long COVID-19 manifestations. The present review summarises current research on different molecular mechanisms in Long COVID pathophysiology and may help identify possible targets or new strategies for the diagnosis and treatment.

Healthcare workers (HCWs) in long-term care (LTC) faced and continue to experience significant emotional and psychological distress throughout the pandemic. Despite this, little is known about the unique experiences of LTC workers. This scoping review synthesizes existing research on the experiences of HCWs in LTC during the COVID-19 pandemic. Following Arksey and O’Malley’s framework, data were extracted from six databases from inception of the pandemic to June 2022. Among 3,808 articles screened, 40 articles were included in the final analysis. Analyses revealed three interrelated themes: carrying the load (moral distress); building pressure and burning out (emotional exhaustion); and working through it (a sense of duty to care). Given the impacts of the pandemic on both HCW wellbeing and patient care, every effort must be made to address the LTC workforce crisis and evaluate best practices for supporting HCWs experiencing mental health concerns during and post-COVID-19.

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..

Cymbidium faberi Rolfe is one of the traditional Chinese orchids with important ornamental value, and the cultivation of Cymbidium faberi Rolfe mutant strains with different appearances is essential to increase its economic value, but at present, the acquisition of Cymbidium faberi Rolfe mutant strains basically relies on natural mutation.The objectives of this research were to mutagenize Cymbidium faberi Rolfe protocorm-like bodies (PLBs) and shoots in vitro using sodium azide (NaN3), and to screen and evaluate mutants in mutagenized Cymbidium faberi Rolfe seedlings using morphological characteristics.Cymbidium faberi Rolfe PLBs and shoots were used as mutagenic materials, and co-cultivated in induced shoots growth medium with the addition of 0.0 (control), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 mg/L and 0.0 (control), 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0 mg/L NaN3 to induce the mutations, and the mortality rates of the PLBs and shoots were increased with the increase of the NaN3 concentration.At 14 d of co-cultivation, PLBs and shoots were most efficiently mutagenized with 1.5 mg/L and 4.0 mg/L NaN3, respectively.After the explants were cultured for 3 months, changes in leaf and flower morphology were observed in some mutants: shorter and thicker leaves, shorter node length, reduced height, and mid-translucent leaves compared with controls; and some Cymbidium faberi Rolfe bloomed prematurely, with single flowers with large, thick petal sepals and small inflorescences, and colours include light green throughout, and a few with purple stamens.This suggests that NaN3 can effectively mutagenise Cymbidium faberi Rolfe PLBs and shoots to satisfy people's demand for Cymbidium faberi Rolfe's ornamental properties while increasing its economic value.

Deep underground laboratories offer advantages for conducting high-precision observations of weak geophysical signals, benefitting from a low background noise level. It is both valuable and feasible to enhance strong, noisy ground electromagnetic (EM) field data using synchronously recorded underground EM signals, which typically exhibit a high signal-to-noise ratio. In this study, we propose an EM field reconstruction method employing a Long Short-Term Memory (LSTM) recurrent neural network with referenced deep underground EM observations. Initially, a deep learning model was developed to capture the time-varying features of underground multi-component EM fields using the LSTM recurrent neural network. Subsequently, this model was applied to process synchronously observed strong, noisy data from other conventional observation systems, such as those at surface, to achieve noise suppression through signal reconstructions. Both theoretical analysis and practical observational data suggest that the proposed method effectively suppresses noise and reconstructs clean EM signals. This method is efficient and time-saving, representing an effective approach to fully utilizing the advantages of deep underground observation data. Furthermore, this method could be extended to the processing and analysis of other geophysical data.

Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer under reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients’ quality of life. A total of 489 advanced rectal cancer patients from the University Hospital Erlangen in Germany were surveyed between May 2010 and March 2022 and asked to fill out the EORTC QLQ-C30 and QLQ-CR38 questionnaire over eight different time points: in the beginning, during and after radiochemotherapy, right before surgery and in yearly intervals after surgery for up to four years. Answers were converted to scores to compare the COVID-19 period to the time before March 2020 focusing on the follow-ups, the developments over time – including by sex and age - and the influence of the TNM cT-stage. Overall, a trend of impaired functional and symptom scores was found across all surveys with few significances (body image -10.6 percentage points (pp) after one year; defecation problems +13.5 pp, insomnia +10.2 pp and weight loss +9.8 pp after three years; defecation problems +11.3 pp after four years). cT4-stage patients lost significantly more weight than their cT1-3-stage counterparts (+10.7 to 13.7 pp). Further studies should be conducted to find possible causes and develop countermeasures for future major infectious diseases.

The long-term laboratory aspects of the effects of COVID-19 on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical-laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older hospitalised in the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. Inflammatory markers such as ferritin > 300 U/L were observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST > 25 U/L, and GGT ≥ 50 or 32 U/L were associated with ALT > 29 U/L. There was a correlation between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID, especially in those hospitalised in the acute phase. In addition, ALT > 29 U/L was associated with other markers of liver injury, such as LDH, GGT, and ferritin.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Transition metal alloys have emerged as promising electrocatalysts due to their ability to modulate key parameters such as d-band electron filling, Fermi level energy, and interatomic spacing, thereby influencing their affinity towards reaction intermediates. However, the structural stability of alloy electrocatalysts during alkaline hydrogen evolution reaction (HER) remains a subject of debate. In this study, we systematically investigate the structural evolution and catalytic activity of the c-Co/Co3Mo electrocatalyst under alkaline HER conditions. We reveal that the instability of the Co3Mo alloy and H0.9MoO3 during alkaline HER leads to the destruction of the crystal structure, resulting in the formation of hexagonal cobalt (h-Co) from hexagonal Co(OH)2 as an intermediate species. Furthermore, we explore the re-adsorption and surface coordination of the Mo element, which enhances the catalytic activity for alkaline HER. This work provides valuable insights into the dynamic behavior of alloy-based electrocatalysts, shedding light on their structural stability and catalytic activity during electrochemical reduction processes

Recently, several reports have emerged describing the long-term consequences of COVID-19 that may affect multiple systems, suggesting its chronicity. As further research is needed, we conducted a longitudinal observational study to report the prevalence and associated risk factors of long-term health consequences of COVID-19 by symptom clusters in patients discharged from the Temporary COVID-19 Hospital (TCH) in Mexico City. Self-reported clinical symptom data were collected via telephone calls over 90 days post-discharge. Among 4670 patients discharged from the TCH, we identified 45 symptoms across eight symptom clusters (neurological; mood disorders; systemic; respiratory; musculoskeletal; ear, nose, and throat; dermatological; and gastrointestinal). We observed that the neurological, dermatological, and mood disorder symptom clusters persisted in >30% of patients at 90 days post-discharge. Although most symptoms decreased in frequency between day 30 and 90, alopecia and the dermatological symptom cluster significantly increased (p<0·00001). Women were more prone than men to develop long-term symptoms and invasive mechanical ventilation also increased the frequency of symptoms at 30-days post-discharge. Overall, we observed that symptoms often persisted regardless of disease severity. We hope these findings will help promote public health strategies that ensure equity in the access to solutions focused on the long-term consequences of COVID-19.