Treatment with calcitriol, the hormonal form of vitamin D, has shown beneficial effects in ex-perimental models of acute lung injury. In this study we aimed to analyze the associations be-tween calcitriol supplementation and the risk of SARS-CoV2 infection or COVID-19 mortality. Individuals ≥18 years old living in Catalonia and supplemented with calcitriol from April 2019 to February 2020 were compared with propensity score matched controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality. Associations between calcitriol supplementation and outcome variables were analyzed using multivariable Cox proportional regression. A total of 8076 patients were identified as being on calcitriol treatment. Advanced chronic kidney disease and hypoparathyroidism were the most frequent reasons for calcitriol supplementation in our population. Calcitriol use was associated with reduced risk of SARS-CoV2 infection (HR 0.78 [CI 95% 0.64-0.94], p=0.010), reduced risk of severe COVID-19 and reduced COVID-19 mortality (HR 0.57 (CI 95% 0.41-0.80), p=0.001) in patients with advanced chronic kidney disease. In addition, an inverse association between mean daily calcitriol dose and COVID-19 severity or mortality was observed in treated patients, independently of renal function. Our findings point out that patients with advanced chronic kidney disease could benefit from calcitriol supplementation during the COVID-19 pandemic.

Tissue resident memory T cells (TRM) were first described in 2009. While initially the major focus was on CD8 TRM, there has been recently an increased interest in defining the phenotype and the role of CD4 TRM in diseases. Circulating CD4 T cells seed tissue CD4 TRM, but there also appears to be an equilibrium between CD4 TRM and blood CD4 T cells. CD4 TRM are more mobile than CD8 TRM, usually localized deeper within the dermis/lamina propria and yet may exhibit synergy with CD8 TRM in disease control. This has been demonstrated in herpes simplex infections in mice. In human recurrent herpes infections, both CD4 and CD8 TRM persisting between lesions may control asymptomatic shedding through interferon gamma secretion, although this has been more clearly shown for CD8 T cells. The exact role of the CD4/CD8 TRM axis in the trigeminal ganglia and/or cornea in controlling recurrent herpetic keratitis is unknown. In HIV, CD4 TRM have now been shown to be a major target for productive and latent infection in cervix. In HSV and HIV co-infections, CD4 TRM persisting in the dermis support HIV replication. Further understanding of the role of CD4 TRM and their induction by vaccines may help control sexual transmission by both viruses.

This review provides a snapshot of chronic bacterial infections through the lens of Burkholderia pseudomallei; detailing its ability to establish multi-nucleated giant cells (MNGC) within the host, leading to the formation of pyogranulomatous lesions. We explore the role of MNGC in melioidosis disease progression and pathology by comparing the similarities and differences of melioidosis to tuberculosis, outlining the concerted events in pathogenesis that lead to MNGC formation, discussing the factors that influence MNGC formation and how they fit into clinical findings reported in chronic cases. Finally, we speculate about future models and techniques that can be used to delineate the mechanisms of MNGC formation and function.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

Background: The coronavirus disease-19 (COVID-19) has spread globally with more than 80,000 people infected, and nearly 3000 patients died. Currently, we are in an urgent need for effective treatment strategy to control the clinical deterioration of COVID-19 patients. Methods: The clinical data of 10 COVID-19 patients receiving short-term moderate-dose corticosteroid (160mg/d) plus immunoglobulin (20g/d) were studied in the North Yard of The First Hospital of Changsha, Hunan from January 17^th to February 27^th, 2020. Epidemiological, clinical, laboratory, radiological findings were analyzed. Results: After treatment with combination of low-dose corticosteroid (40-80mg/d) and immunoglobulin (10g/d), patients’ lymphocyte count (0.88±0.34 vs 0.59±0.18, P<0.05), oxygenation index including SPO₂ (94.90±2.51 vs 90.50±5.91, P<0.05) and PaO₂/FiO₂ (321.36±136.91 vs 129.30±64.97, P<0.05) were significantly lower than pre-treatment, and CT showed that the pulmonary lesion deteriorated in all patients. While after treatment of short-term moderate-dose corticosteroid plus immunoglobulin, patients’ APACHE Ⅱ score (9.10±6.15 vs 5.50±9.01, P<0.05), body temperature (37.59±1.16 vs 36.46±0.25, P<0.05), lymphocyte count (0.59±0.18 vs 1.36±0.51, P<0.05), Lactate dehydrogenase (419.24±251.31 vs 257.40±177.88, P<0.05), and C-reactive protein (49.94±26.21 vs 14.58±15.25, P<0.05) significantly improved compared with post-treatment with low-dose therapy. In addition, oxygenation index including SPO₂ (90.50±5.91 vs 97.50±1.18, P<0.05), PaO₂ (60.47±14.53 vs 99.07±34.31, P<0.05), and PaO₂/FiO₂ (129.30±64.97 vs 340.86±146.72, P<0.05) significant improved. Furthermore, CT showed that pulmonary lesions obviously improved in 7 patients. After systematic therapy, 4 out of 10 COVID-19 patients recovered and discharged. Conclusions: Short-term moderate-dose corticosteroid plus immunoglobulin is effective for reversing the continued deterioration of COVID-19 patients who failed to respond to the low-dose therapy. Funding: This work was supported by the Innovative Major Emergency Project Funding against the New Coronavirus Pneumonia in Hunan Province (Dr. Ji-Yang Liu, number 2020SK3014; Dr. Yuan-Lin Xie, number 2020SK3013).

The bacterial flagellum is a motility organelle, consisting of a long helical filament as a propeller and a rotary motor that drives rapid filament rotation to produce thrust. Salmonella enterica serovar Typhimurium has two genes of flagellin, fljB and fliC, for flagellar filament formation and autonomously switches their expression at a frequency of 10^-3–10^-4 per cell per generation. We report here differences in their structures and motility functions under high viscosity conditions. A Salmonella strain expressing FljB showed a higher motility than the one expressing FliC under high viscousity. To examine the reasons for this motility difference, we carried out structural analyses of the FljB filament by electron cryomicroscopy and found that the structure is nearly identical to that of the FliC filament except for the position and orientation of the outermost domain D3 of flagellin. The density of domain D3 was much lower in FljB than FliC, suggesting that domain D3 of FljB is more flexible and mobile than that of FliC. These differences suggest that domain D3 plays an important role not only in changing antigenicity of the filament but also in optimizing motility function of the filament as a propeller under different conditions.

Although there are extensive literature reports on the use of gold nanoparticle (AuNP) based homogeneous assays for detection of biomolecules, very few experimental description and procedures involving their preparation are described. In this study, AuNPs conjugated to Bovine Serum Albumin or Envelope protein from Dengue II were developed as a homogeneous immunoassay for antibody detection. We report here optimization of key parameters to prepare an immunoassay like conjugation protein concentration, centrifugation time, electrolyte addition and assay temperature. We determined that saturating protein concentrations improved AuNPs surface coverage and uniformity of the assay and addition of sodium chloride improved sensitivity of the antibody detection method and assay stability. Furthermore, we showed that dynamic light scattering can be used to monitor changes in gold nanoparticles in the preparation and detection steps. Additionally, numerical simulations of the plasmonic optical response of AuNPs were carried out to scan for size-dependent response of the AuNPs. The AuNPs homogeneous immunoassay developed was further used in the detection of antibodies in vitro to detect Dengue virus infection.

Viral infection can regulate the cell cycle, thereby promoting viral replication. Hijacking and altering the cell cycle are important for the virus to establish and maintain latent infection. Previously, Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) latently infected P8-Se301-C1 cells, which grew more slowly than Se301 cells and interfered with homologous SeMNNPV superinfection, were established. However, the effects of latent and superinfection with baculoviruses on cell cycle progression remain unknown. In this study, the cell cycle profiles of P8-Se301-C1 cells, and SeMNPV or Autographa californica mutiple nucleopolyhedrovirus (AcMNPV) infected P8-Se301-C1 cells were characterized by flow cytometry. The results showed that replication-related genes MCM4, PCNA, and BAF were down-regulated (p < 0.05) in P8-Se301-C1 cells and the S phase of P8-Se301-C1 cells was longer than that of Se301 cells. P8-Se301-C1 cells infected with SeMNPV did not arrest in G2/M phase and or affect the expression of Cyclin B and cyclin-dependent kinase 1 (CDK1). Furthermore, when P8-Se301-C1 cells were infected with SeMNPV after synchronized treatment with hydroxyurea and nocodazole, light microscopy and qRT-PCR analysis showed that compared with unsynchronized cells and S and G2/M phase cells, SeMNPV-infected P8-Se301-C1 cells in G1 phase induced G2/M phase arrest, and the amount of virus adsorption and intracellular viral DNA replication were significantly increased (p < 0.05). In addition, the BV production and the OB containing cells were both increased at 120 h post-infection (p < 0.05). The expression of Cyclin B and CDK1 was significantly down-regulated at 48 h post infection (p < 0.05). Finally, arrest of SeMNPV-infected G1 phase cells in the G2/M phase increased BV production (p < 0.05) and the number of OB containing cells. In conclusion, G1 phase infection and G2/M arrest are favorable to SeMNPV proliferation in P8-Se301-C1 cells, thereby alleviating the homologous superinfection exclusion. The results contribute to a better understanding of the relationship between baculoviruses and insect cell cycle progression regulation.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflamation and to explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. The study included 139 patients who were enrolled between January-June 2021, mean age 46.7±15.2 years, 68 were men, 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work up, lab. analyses, cardiac ultrasound, and CMR on 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE, (4.3±0.23 vs 3.2±0.14g/L, p<0.05; respectively), as well as D-dimer (1.8±0.3 vs 0.8±0.1 mg/L FEU). Also troponin was statistically significantly higher in patients with myocardial LGE (13.1±0.4ng/L) compared to those with normal myocardium (4.9±0.3ng/L, p<0.001). We demonstrated chest pain, fatigue and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.

The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human wild-type virus. The samples were then incubated with cells expressing the ACE2 receptor and therefore very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, to completely inhibit SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in the in vivo skin model. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of COVID-19 disease.

Objective: Spontaneous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA vaccination causes a marked increase in antibody titer because of the combined effect of vaccine and infection (“hybrid immunity”). In this study, we discuss the significance of the mRNA vaccine booster inoculation that has been repeatedly performed in Japan.Methods: We describe the temporal trends of antibody titers in cases in which antibody titers were markedly increased by hybrid immunization.Results: The antibody titer increased with hybrid immunization and tended to decrease with time. However, several cases maintained high antibody titers for approximately one year after coronavirus disease 2019 (COVID-19 diagnosis), even without booster vaccination.Conclusions: Most Japanese patients naturally infected with COVID-19 were infected after mRNA vaccination, and many maintained high antibody titers due to hybrid immunity. The significance of additional vaccination in hybrid-immunized cases is highly questionable regarding cost-effectiveness and risk-benefit.

The Covid-19 crisis has been one of the most relevant economic shocks in the history of the modern economy, mainly due to the restrictions on travel and social interaction taken by the authorities (quarantines, closure of schools, artistic activities, bars, and restaurants, capacity in stores), to reduce the transmission of the virus (Sars-Cov2), having consequences on the national productions of all countries (about 7% for the loss of GDP worldwide). In our study, we analyze, through clustering methods, the effects of the level of contagion, economic projections, and economic mitigation measures taken by governments for managing the pandemic. According to the analyses, it can be concluded that a low infection rate implies a lower loss of product and economic savings when applying economic mitigation measures, taking relevance in the management of sanitary measures to reduce the transmission of the virus (and the temporality of these).

This paper offers an in-depth exploration of the complex relationship between seasonality and Autism Spectrum Disorder (ASD). It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of seasonality as an environmental factor that influences the etiology of ASD. The discussion encompasses various factors, including birth months, maternal health, dietary choices, and vitamin D deficiency, and delves into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how seasonality factors may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

Enterocins are bacteriocins synthesized by Enterococcus strains that show an interesting antimi-crobial effectiveness against foodborne pathogens such as Listeria monocytogenes. The objectives of this study were identify and analyze the expression of enterocin genes of Enterococcus isolated from breast-fed infants and evaluate the ability to inhibit three human isolates of virulent Lis-teria monocytogenes, as well as some probiotic bacteria. The susceptibility of the strains of L. mon-ocytogenes to fifteen antibiotics was tested, detecting resistance to cefoxitin (constitutive-ly resistant), oxacillin and clindamycin. Production of enterocins A, B and P were observed in Enterococcus faecium isolates, and enterocin AS-48 in an Enterococcus faecalis isolate. AS-48 showed antilisterial activity by itself, while the joint action of enterocins A and B, or B and P was neces-sary for inhibiting L. monocytogenes, demonstrating a synergistic effect of those combinations. The presence of multiple enterocin genes does not assured the inhibition of L. monocytogenes strains. However, the expression of multiple enterocin genes showed a good correlation with the inhibition capacity of these strains. Furthermore the potential beneficial strains of lactobacil-li and bifidobacteria examined were not inhibited by any of the enterocins produced individu-ally or in combination, with the exception of Bifidobacterium longum BB536, which was inhibited by enterocin AS-48 and the joint production of enterocins A and B or B and P. The enterocins studied here could be candidates for developing alternative treatments against antibi-otic-resistant bacterial infections. Moreover, these selected enterocin-producing E. faecium strains isolated from breast-fed infants could be used as probiotic strains due to their antilisterial effect as well as the absence of virulence factors.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

Dogs play an important role in the transmission of Leishmania infantum but epidemiologic and clinical studies of canine tegumentary leishmaniasis (CTL) are scarce. In an endemic area of human American Tegumentary Leishmaniasis (ATL) caused by Leishmania braziliensis, we determine the prevalence and incidence of both CTL and subclinical (SC) L. braziliensis infection in dogs and evaluated if the presence of dogs with the CTL or the SC L. braziliensis infection is associated with the occurrence of human ATL. SC infection in healthy animals and CTL in animals with ulcers was determined by PCR on biopsied healthy skin or on the ulcer or detecting antibodies against soluble leishmania antigen. We compared the occurrence of human ATL in homes with dogs with CTL or SC infection with control homes without dogs or with dogs without CTL or SC infection. The prevalence of SC infection was 35% and of CTL 31%. The incidence of SC infection in dogs was 4.6% and of CTL was 9.3%. The frequency of ATL in humans was 50% in homes with infected dogs and 13% in homes without L. braziliensis infection in dogs. CTL and SC infection is highly prevalent, and dogs may participate in the transmission chain of L. braziliensis.

Since the first description of COVID-19 infection, among clinical manifestations of the disease including fever, dispnea, cough, fatigue, it was observed a high incidence of thromboembolic events potentially evolving towars ARDS and COVID-associated-coagulopathy (CAC).The hypercoagulation state is based on an interaction between thrombosis and inflammation. The so-called CAC represents a key aspect in the genesis of organ damage from SARS-CoV-2. The prothrombotic status in COVID-19 disease can be explained by the increase of coagulation levels of D-dimer, lymphocytes, fibrinogen, IL-6 and prothrombin time. Several mechanisms have been hypothesized to explain this hypercoagulable process such as inflammatory cytokine storm, platelet activation, endothelial dysfunction and stasis for a long time. The purpose of this narrative review is to provide an overview of the current knowledge on the pathogenic mechanisms of coagulopathy that may characterize COVID-19 infection and inform on new areas of research. New vascular therapeutic strategies are also reviewed.

Valley fever or coccidioidomycosis is a pulmonary infection caused by several species of coccidi-oides (Cocci) fungi that is endemic to California and Arizona. Skeletal coccidioidomycosis ac-counts for about half of disseminated infections, with the vertebral spine being the preferred site of dissemination. Most cases of skeletal coccidioidomycosis progress to bone destruction or spread to adjacent structures such as joints, tendons, and other soft tissues causing significant pain and restricting mobility. Manifestations of such cases are usually non-specific, making di-agnosis very challenging, especially in non-endemic areas. In this review, we explore case reports of dissemination of coccidioidomycosis to bones and/or joints to highlight key differential fea-tures with other conditions or diseases and highlight opportunities for mechanistic and pre-clinical studies that can help improve diagnostics, prognostics, and treatments.

Abstract. Marek's disease virus is an oncogenic avian herpesvirus and the problem of oncogenicity of this virus for humans remains unexplored. This pathology appeared in broiler chickens of 30 days and older, that is from now on the contact with poultry meat carries the risk of infecting people. This article analyzes the risks of the emergence of the epidemic potential of the Marek's disease virus in the Russian Federation taking into account the characteristics of modern pig and poultry farming. It was found that COVID 19 can serve as an additional factor in reducing the resistance of the population to herpesvirus infections. The COVID 19 epidemic is accompanied by folic acid deficiency which also increases the risk of contamination of diseases associated with DNA viruses, including an extended risk of animal viruse infection. Since, according to our estimates, Marek's disease occurred in at least 25% of broiler poultry farms in the Russian Federation, a possible expand in mortality from neoplasms of the reproductive system for the Russian Federation as a whole can contribute to the dynamics of oncological diseases of reproductive organs and breast cancer. Since 2011 a contagious form of intestinal pathology, vesicular enteritis, has widely spread at poultry farms in the Russian Federation. During periods of extending incidence of vesicular enteritis, we recorded cases of inflammation of the facial nerves and subfebrile temperature in contact persons, bursts of oncological diseases in veterinary personnel (ovarian cancer, breast cancer), abnormal and synchronous increases in the incidence of infectious larengotracheitis and Marek's disease in chickens under the age of 40 days which requires additional monitoring studies.

In French Polynesia, Wuhan, Delta and Omicron SARS-CoV-2 variants-of-concern (VOCs) caused epidemics with variable severities. We assessed the prevalence and titers of anti-SARS-CoV-2 antibodies related to natural infection and/or vaccination, from a representative sample (N=673) of the adult population of Tahiti recruited during November-December 2021 (after the Delta outbreak and just before the Omicron epidemic). Of the 673 participants tested, 644 (95.7%) had detectable antibodies against SARS-CoV-2-S and/or -N proteins resulting from natural infection and/or vaccination, and 388 (57.7%) were positive only for the detection of anti-N antibodies indicating natural infection. SARS-CoV-2 seroprevalence extrapolated to the adult population of Tahiti was estimated at 95.9%. Concentrations of anti-SARS-CoV-2-S antibodies significantly increased with age, number of self-reported SARS-CoV-2 infections (0 or ≥1), and number of COVID-19 vaccine doses (0, 1, 2, or 3) received by the participants. Elderly people, who are at higher risk of severe outcomes, had received more vaccine doses than younger individuals both in our sample and in the general population. The high level of antibody responses related to past infections and vaccination, especially booster doses, has likely contributed to reducing the severity of the Omicron outbreak in French Polynesia.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

Aedes (Stegomyia) albopictus is a mosquito native to Southeast Asia. Currently, it has a wide distribution in America where natural infection with arboviruses of medical and veterinary importance has been reported. In spite of their importance in the transmission of endemic arbovirus, basic information of parameters affecting their vectorial capacity is poorly investigated. The aim of the work was to update the distribution range of Ae. albopictus in the Americas, review the blood-feeding patterns and compare the minimum infection rate (MIR) of the dengue virus (DENV) between studies of vertical and horizontal transmission. The current distribution of Ae. albopictus encompasses 21 countries in the Americas. Extensive review has been conducted for the blood-feeding patterns of Ae. albopictus. The results suggest that the mosquito is capable of feeding on 16 species of mammals and five species of avian. Humans, dogs, and rats are the most common host. Eight arboviruses with the potential to infect humans and animals have been isolated in Ae. albopictus. In the United States of America (USA), Eastern equine encephalitis virus, Keystone virus, La Crosse Virus, West Nile virus, and Cache Valley virus were isolated in the Asian mosquito. In Brazil, Mexico, Colombia, and Costa Rica, DENV (all serotypes) has been frequently identified in field-caught Ae. albopictus. Overall, the estimated MIR in Ae. albopictus infected with DENV is similar between horizontal (10.95) and vertical transmission (8.28). However, in vertical transmission, there is a difference in the MIR values if the DENV is identified from larvae or adults (males and females emerged from a collection of eggs or larvae). MIR estimated from larvae is 14.04 and in adults is 4.04. In conclusion, it has to be highlighted that Ae. albopictus is an invasive mosquito with wide phenotypic plasticity to adapt to broad and new areas, it is highly efficient to transmit the DENV horizontally and vertically, it can participate in the inter-endemic transmission of the dengue disease, and it can spread zoonotic arboviruses across forest and urban settings.

The aim of the work was to update the distribution range of Aedes (Stegomyia) albopictus Skuse in the Americas, review the blood-feeding patterns and compare the minimum infection rate (MIR) of the dengue virus (DENV) between studies of vertical and horizontal transmission. The current dis-tribution of Ae. albopictus encompasses 21 countries in the Americas. Extensive review has been conducted for the blood-feeding patterns of Ae. albopictus. The results suggest that the mosquito is capable of feeding on 16 species of mammals and five species of avian. Humans, dogs, and rats are the most common host. Eight arboviruses with the potential to infect humans and animals have been isolated in Ae. albopictus. In the United States of America (USA), Eastern equine encephalitis virus, Keystone virus, La Crosse Virus, West Nile virus, and Cache Valley virus were isolated in the Asian mosquito. In Brazil, Mexico, Colombia, and Costa Rica, DENV (all serotypes) has been frequently identified in field-caught Ae. albopictus. Overall, the estimated MIR in Ae. albopictus infected with DENV is similar between horizontal (10.95) and vertical transmission (8.28). However, in vertical transmission, there is a difference in the MIR values if the DENV is identified from larvae or adults (males and females emerged from a collection of eggs or larvae). MIR es-timated from larvae is 14.04 and in adults is 4.04. In conclusion, it has to be highlighted that Ae. albopictus is an invasive mosquito with wide phenotypic plasticity to adapt to broad and new areas, it is highly efficient to transmit the DENV horizontally and vertically, it can participate in the inter-endemic transmission of the dengue disease, and it can spread zoonotic arboviruses across forest and urban settings.

Background: Since the previous study dealing with the case fatality ratio and infection fatality ratio caused by COVID-19, the author has received many comments that prompted the question: "Why did an optimistic prognosis fail?" To answer this question, a more detailed and expanded analysis was carried out in a new study. Objective: To evaluate the dynamics of monthly numbers of cases, deaths, tests and CFR worldwide during three phases of the COVID-19 pandemic. Material and Methods: Twenty three sets of databases, dated the 22nd of each month from January 2020 to November 2021, for 213 countries were collected from the Worldometer website. The number of cases, deaths, tests, CFR, IFR, etc. were counted for various periods of time for each of the 213 countries, then results related to different periods of time were compared. Results: The analysis of the main epidemiological parameters led to the division of three phases of the global pandemic evolution. The first phase (23.01.20-22.07.20), the second phase (23.07.20-22.01.21) and the third phase (23.01.21-22.07.21) were different in terms of the number of tests performed, new cases, and mortality due to COVID-19. By the end of the second phase, the worldwide statistics indicated the imminent end of the pandemic, but the third phase was characterized by a sudden rise in the number of new cases and deaths that could not be explained rationally. The most dramatic evolution of the epidemic curve occurred in the countries where doctors had successfully battled COVID-19 during the first two phases of the pandemic. Conclusions: Despite the decrease in overall death numbers during the latest months analyzed, additional study is necessary to identify the cause for the increase in the number of new cases and deaths during the third phase of the pandemic. Only complete information regarding the positive and negative impact of medical and non-medical methods of diagnostics and prophylaxis of COVID-19 can help to organize effective measures to end the current pandemic and prevent a similar one from occurring in the future. Presumably, there are several causes of the negative evolution of the current pandemic, including the overreliance on PCR tests, application of non-specialized premises for quarantine and treatment, decrease in herd and individual immunity, inadequate change of therapeutic protocols, and ignoring prophylactic treatment. It can be suggested that the use of immunemodulatory drugs, for example, thymus extract or thymic peptides, in groups of people with compromised immunity is necessary, and prophylactic and therapeutic protocols should be changed from the 'standard' types to 'personalized' ones.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines, however, has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease alongside the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out with the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms from thrombosis following vaccination was also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

In the context of the COVID-19 pandemic, thousands of healthcare workers (HCWs) infected with COVID-19 have lost their lives worldwide. At the early stage of the epidemic, when COVID-19 was still not considered as a pandemic, a large number of Chinese HCWs were infected. Officials reported that more than 3,000 HCWs in Hubei contracted the virus at the early stage of the outbreak due to limited knowledge of the virus. Following reports of overloaded local hospitals, more than 42,000 medical staff, including those from the military, were dispatched to Hubei from across the country. At the peak of the fight, one in 10 intensive care medics in China were working in Wuhan. During fighting against COVID-19 in China, although a large number of HCWs were infected by SARS-CoV-2 in the early stages of the epidemic, the timely adoption of measures indicated that, a faster rate of diagnosis could be achieved, patients were isolated in-time, HCWs’ safety was prioritized, training on basic protective knowledge and unified management of HCWs was strengthened, and effective protective measures were implemented. This resulted in the accomplishment of zero SARS-CoV-2 infection among the 42,632 members of the national medical teams sent to Hubei, and the number of COVID-19 cases among HCWs in local hospitals also significantly decreased, thereby indicating that hospital-acquired infections of SARS-CoV-2 among HCWs are fully preventable.

The development of 3D cerebral brain organoids which accurately resemble aspects of the human brain permits a more accurate characterization of physiological processes and neurological diseases. Cerebral organoids can be grown from stem cell lines with various genetic backgrounds allowing multiple neurodegenerative diseases to be modeled. While dysfunction in neurotransmission of patients with neurodegenerative diseases is expected, the impact of chronic neurodegeneration on the response to viral infection of the CNS is poorly understood. For instance, several mosquito-borne viruses like Dengue virus and West Nile Virus cause post-viral parkinsonism. How CNS infection might impact a host with inherent CNS dysfunction such as Parkinson’s Disease in poorly understood. This preliminary, observational study aimed to understand dysfunction in intrinsic and innate expression of a patient with a neurodegenerative disease and a non-affected individual in relation to potential viral infection in the CNS. Cerebral organoids were generated from human induced pluripotent stem cells with a normal genetic background or with idiopathic Parkinson’s Disease. After differentiation and maturation, organoid size, gene expression and immunofluorescence were evaluated to assess neurotransmission and innate immunity. While there was no significant difference in size of the organoids with a normal or Parkinson’s genetic background, gene expression studies identified multiple differences in innate immunity and neurotransmission. Immunofluorescence also identified differences in protein expression related to neurotransmission and innate immunity. Of note, organoids derived from a Parkinson’s patient exhibited endogenous up-regulation of dopamine and muscarinic acetylcholine receptors, GABA, glycine, and glutamate targets, and the majority of cytokines. This expression pattern suggests a chronic state of neuroexcitation and neuroinflammation in this population of organoids.

We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.

Background: Dental professions are at high risk of contracting novel corona virus (COVID-19) infections during the dental procedure due to the droplets and aerosols generated during various dental procedures on infected patients. To prevent and avoid the cross-infection of the infection to dental professionals or the patients attending the dental clinic, good knowledge of the infection and its prevention mechanisms is mandatory among the professionals. Until to date, there is no pooled estimate on the knowledge,attitude and practice (KAP) of dental professionals to COVID-19 in the globe. Hence, this study aimed to determine the pooled estimate of KAP of dental professionals in this pandemic disease. Methods: Article search was done electronically using Medline, Scopus, Web of Science, EMBASE, SciELO and Google Scholar from June 1, 2020 to August 20, 2020. All studies that assessed the KAP of dental professionals to COVID-19 were searched and included in this review after passing the inclusion criteria. The pooled analysis of their knowledge (sign and symptom, mode of transmission and prevention mechanisms), attitude (their concern, intention to treat suspected patients) and practice (face mask usage, hand washing and alcohol based hand rub usage, handshaking practice, deferred procedures and checkup of patients temperature) was computed using RevMan 5.3 and random effect model was used. The presence of publication bias was assessed using the funnel plot. Results: Twelve articles with a total of 5,362 study participants were included in this study. The pooled estimate revealed that 59.91% of the dental professionals had good knowledge of the signs and symptoms of COVID-19. Two-third of dental professionals know the prevention mechanisms of the infection, and 70.13% had enough knowledge of the transmission modalities of the infection. The professional attitude revealed that only 36.43% of the participants had intention to treat a patient with cough or suspected COVID-19 (36.43%, 95%CI: 8.57, 64.29). Moreover, 47.85% of the dentists were concerned about their life, and the fate of their profession due to this pandemic disease (47.85%, 95%CI: 26.74, 68.97). The pooled analysis showed only 50.86% (95%CI: 18.64, 83.09) of the study participants worn face mask and 52.63% (95%CI: 10.54, 94.71) had avoided handshaking practice during this pandemic period. Non-emergency dental procedures were canceled by 83.98%. Conclusion: The dental professional KAP is not optimal. Thus, dental professionals should be aware of the recently updated knowledge about COVID-19 and practice according to the standards of treatment guidelines, and the recommended infection control measures in dental settings. Moreover, as saliva and droplets are the major sources of infection, dentists should follow essential protocols to regulate droplet and aerosol contamination in the dental practice

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). Overall, severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 10²-10⁵ gc/ml) and feces (ca. 10²-10⁷ gc/ml) is much lower than in nasopharyngeal fluids (ca. 10⁵-10¹¹ gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the GI tract and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that over eight million global cases of COVID-19 have occurred, but exposure to feces or wastewater has never been implicated as a transmission vector.

Global differences in changes in the numbers of population-adjusted daily test-positive cases (NPDP) and deaths (NPDD) by COVID-19 were analyzed for 49 countries, including developed and developing countries. The changes as a proportion of national population were compared, adjusting by the beginning of test-positive cases increase (BPI) or deaths increase (BDI). Remarkable regional differences of more than 100 fold in NPDP and NPDD were observed. The trajectories of NPDD after BDI increased exponentially within 20 days in most countries. Machine learning analysis suggested that NPDD on 30 days after BDI was the highest in developed Western countries (1180 persons per hundred million), followed by countries in the Middle East (128), Latin America (97), and Asia (7). Furthermore, in Western countries with positive rates of the PCR test of less than 7.0%, the increase in NPDP was slowing-down two weeks after BPI, and subsequent NPDD was only 15% compared with those with higher positive rates, which suggested that the situation of testing might have affected the velocity of COVID-19 spread. The causes behind remarkable differences between regions possibly include genetic factors of inhabitants because distributions of the race and of the observed infection increasing rates were in good agreement globally.

The fast spread of COVID-19 constitutes a worldwide challenge to the public health, educational, and trade systems, affecting the overall wellbeing of human societies. The high transmission and mortality rates of this virus, and the unavailability of a vaccine or treatment, resulted in the decision of multiple governments to enact measures of social distancing. Thus, it is of general interest to consider the validity of the proposal for keeping a social distancing of at least 2 m from other persons to avoid the spread of COVID-19. The exposure to the bioaerosol can result in the deposition of the pathogen in the respiratory tract of the host causing disease and an immunological response. In the atmospheric context, the work evaluates the effect of aerodynamic diameter (size) of particles in carrying RNA copies of the novel coronavirus. A SARS-CoV-2 carrier person talking, sneezing, or coughing at distance of 2 m can still provide a pathogenic bioaerosol load with submicron particles that remain viable in air for up to 3 hours for exposure of healthy persons near and far from the source in a stagnant environment. The deposited bioaerosol creates contaminated surfaces, which if touched can act as a path to introduce the pathogen by mouth, nose, or eyes and cause disease.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

Persistent cervical infection with high-risk Human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. In order to assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95%CI: 1.365-2.332, p<0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.

The human coronaviruses (CoV) include HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1, some known for decades. The severe acute respiratory syndrome (SARS) CoV briefly emerged into the human population but was controlled. In 2012 another novel severely human pathogenic CoV – Middle Eastern Respiratory Syndrome (MERS)-CoV was identified in the Kingdom of Saudi Arabia, where 80% of over 2,000 human cases have been recorded across five years. Targeted research remains key to developing control strategies for MERS-CoV, a cause of mild illness in its camel reservoir. A new therapeutic toolbox being developed in response to MERS is also teaching us more about how CoVs cause disease. Travel-related cases continue to challenge the world’s surveillance and response capabilities and more data are needed to understand unexplained primary transmission. Signs of genetic change have been recorded but it remains unclear whether any impact on clinical disease. How camels came to carry the virus remains academic to the control of MERS. To date, human-to-human transmission has been inefficient, but virus surveillance, characterisation and reporting are key to responding to any future change. MERS-CoV is not currently a pandemic threat; it is spread mainly with the aid of human habit and error.

Human papillomavirus (HPV) is one the most common sexually transmitted infections (STI), spreading through direct sexual contact to oropharynx and anogenital regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals’ HPV infection causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). Over 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. They present some unique infection driven cellular and molecular features, in comparison to other head and neck carcinomas (HNC), constituting distinct preventive, therapeutic and prognostic strategies - with significant strides made in this area. However, HPV+OPC are routinely detected at a later stage, adding to the disease burden and overall survival. In this review, we provide a summary of HPV from a STI to malignant transformation, while also parsing through the immune response environment. We further collate key literature around infection sites, diagnostics and clinical management, while throwing light on the current state of epidemiology, transmission, screening and prevention strategies. Indeed, our improving understanding of the disease’s molecular biology has added some success to the prognostic outcomes of certain HPV+OPC across clinical trials examining targeted therapeutics and immunotherapy. This work is directed towards improving our current understanding of HPV and associated oncogenic landscape, to guide screening, early detection, triaging and further prevention and management strategies.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is a rare immune-mediated relapsing-remitting disease of the central nervous system. The usage of rituximab, to prevent NMOSD relapses, is common in Sweden, but the knowledge on long-term efficacy and risk for severe infections are limited. We performed a retrospective cohort study with medical chart review of rituximab-treated NMOSD patients at the Karolinska University Hospital, Sweden, to assess the occurrence of relapses and severe infectious events (SIE). Furthermore, we collected data on CD19+ lymphocyte, and IgG levels during therapy. A total of 42 NMOSD patients; 24 with aquaporin -4 antibodies (AQP4+), eight with myelin oligodendrocyte glycoprotein antibodies (MOG+) and 10 with absence of antibodies (double-seronegative) were included. During a mean treatment time of 4.4 years, 37% AQP4+, 75% MOG+, and 60% double-seronegative patients experienced 1 relapse. SIEs were common with 46% of AQP4+, 25% of MOG+, and 40% of double-seronegative patients affected. Incomplete CD19+ lymphocyte suppression did not predict a relapse and there was no correlation between IgG levels and SIEs. In conclusion, our data demonstrated a high risk for both relapses and SIEs in rituximab-treated NMOSD patients highlighting the need for close clinical vigilance of disease activity and infections during treatment.

Objectives. Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. Previous literature revealed limited data concerning the outcomes. This study aimed to establish a risk-scoring system. Methods. A total of 53 patients were included in the study from a multi-centered database in Taiwan. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to 1-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic curve was used to express the performance of our IFSD scoring model. Results. Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or < 0.4 103/uL, hemoglobin < 8 g/dL, and evidence of candidemia. 1-year mortality rates for patients with IFSD Scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the receiver operating characteristic curve was 0.823. Conclusions. We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of 1-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

Innovative strategies to control malaria are urgently needed. Exploring the interplay between the Plasmodium sp. parasites and host red blood cells (RBC) offers opportunities for novel antimalarial interventions. Pyruvate kinase deficiency (PKD), characterized by heightened 2,3-diphosphoglycerate (2,3-DPG) concentration, has been associated with protection against malaria. Elevated 2,3-DPG levels, a specific mammalian metabolite, may hinder glycolysis, prompting us to hypothesize its potential contribution to PKD-mediated protection. We investigated the impact of the extracellular supplementation of 2,3-DPG on the Plasmodium falciparum intraerythrocytic developmental cycle in vitro. Results showed an inhibition of parasite growth, resulting from significantly less progeny from 2,3-DPG-treated parasites. We analyzed differential gene expression and the transcriptomic profile of P. falciparum trophozoites, from in vitro cultures submitted or not submitted to the action of 2,3-DPG, using Nanopore Sequencing Technology. The presence of 2,3-DPG in the culture medium was associated to a significant differential expression of 71 genes, mostly associated to GO terms nucleic acid binding, transcription, or monoatomic anion channel. Further, several genes related to the cell cycle control were downregulated in treated parasites. These findings suggest that the presence of this RBC-specific glycolytic metabolite impact the expression of genes transcribed during the parasite trophozoite stage and the number of merozoites released from individual schizonts, which supports the potential role of 2,3-DPG in the mechanism of protection against malaria by PKD.

Background: Urinary tract infection (UTI) is one of the commonest bacterial infections among reproductive age females. Untreated UTI in reproductive age female is associated with sexual dysfunction, cystitis, pyelonephritis and Pelvic inflammatory disease. At present, the antimicrobial resistance emergency has quadrupled worldwide and poses a serious threat to the treatment of patients. Thus, this study aimed to determine bacterial profile, antibiotic susceptibility pattern and associated risk factors of urinary tract infection among reproductive age females attending the Logbaba District Hospital Methods: A hospital-based cross-sectional study was conducted from January – July, 2023. Convenient sampling was employed to recruit 259 reproductive age females. Sociodemographic and risk factors information were obtained using a well-structured questionnaire. Mid-stream urine was collected and inoculated on cystine lactose electrolyte deficient media. Isolates were identified using API 20. Antibiotic sensitivity testing was performed using modified kirby-bauer susceptibility testing technique. Multivariate logistic regression model was used to assessed risk factors. A p-value < 0.05 was considered as statistically significant. Results: The overall prevalence of UTI among reproductive age females was 82/259 (31.66%). Symptomatic and asymptomatic patients reported a prevalence of 50/121(41.32%) and 32/138 (23.19%), respectively. Ages ranging from 21-30 years (AOR: 2.53 ,95% CI 1.32 – 4.43, p=0.006) and 31 – 40 years (AOR: 0.19 , 95% CI: 0.14- 0.54; p <0.0001), student (AOR: 1.8, 95% CI: 1.21 - 2.75; p = 0.010), history of UTI (5.34, 95% CI = 1.86 - 18.15; p = 0.03), symptomatic (AOR = 2.86, 95% CI1.78 - 4.67, p <0.0001) and secondary education (AOR: 0.13, 95% CI 0.08 - 0.32; p<0.0001) were predictors to UTI. Klebsiella Pneumoniae was the most frequent species 27 (32.9%), follow by E coli 22(26.8%), Staphylococcus aureus 16 (19.5%), CONS 8 (9.8%), Proteus mirabilis 6 (7.3 %) and Pseudomonas aeruginosa 3(3.7%). Majority of the isolates were sensitive to cefotaxime (87.80%), imipenem (85.7%), vancomycin (79.27%), Ofloxacillin (76.83%), Ceftriaxone (75.61%), Ciprofloxacin (74.39%), Gentamicin (71.95%) and Doxycycline (69.51%), and resistant to Amoxicillin (51.22%), cotrimoxazole (47.56%) and Azithromycin (31.71%) , All the isolates were multidrug drug resistant (100%) and Klebsiella Pneumoniae and E coli were the most multidrug drug resistant species Conclusion: In the present study, the prevalence of urinary tract infection among reproductive age females was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection in the study area.

Vancomisin resistant enterococcus(VRE), is a resistant microorganism which colonizates and causes infections in hospitalized patients. It was aimed to show the spread of vancomycin-resistant Enterococcus (fVREfm) step-by-step in all intensive care units, which started with the growth of vancomycin-resistant Enterococcus faecium (VREfm) on 02.12.2021 in the blood culture of a patient hospitalized in the anesthesia intensive care unit of our hospital and was found to have reached epidemic size in the surveys. Rectal swab samples were taken from all patients hospitalized in intensive care units, VRE colonization was determined and the VanA and VanB resistance genes associated with vancomycin resistance of VREfm isolates were determined by PCR method, and clonal association analysis was performed by Arbitrarily Primed-PCR (AP-PCR) and Pulsed-Field Gel Electrophoresis. In our study, VRE was detected in 61 of 2601 rectal swab samples. 54 (85.52%) of the VRE isolates were Enterococcus faecium, 3 (4.91%) was Enterococcus faecalis, 3 (4.91%) was Enterococcus gallinorum, 1 (1.63%) was Enterococcus casseliflavus. It was determined that all of the 54 VREfm isolates, which were the most detected among all VRE isolates, carried the vanA gene. In the clonal association analysis of the isolates by AP-PCR and PFGE methods, it was found that they had 12 different genotypes, 48 of them were included in any cluster, the clustering rate was 88.8%, and the largest cluster was genotype 1 cluster with 36 isolates. Of the 54 patients with VREfm isolated recently, 18.51 percent of the clinical samples were isolated before the survey, and 9.24% were isolated after the survey. It was determined that 100% of VREfm isolates were resistant to ampicillin, levofloxacin, ciprofloxacin, high-level gentamicin, trimethoprim-sulfamethoxazole, teicoplanin, 7.4% to tigecycline and 1.85% to linezolid. In our study, in the clonal association analysis performed by isolating VREfm in rectal swab samples, it was found that 88.8% of the samples were indistinguishably similar and the increase in the number of VREfm infections after the index case in our hospital was associated with the epidemic. VREfm infections cause long term hospitalization, costs and also deaths, which shows the seriousness of the event, and the importance of the combination of epidemiological and molecular analysis in epidemic research.

The inaugural AIDS Program in Brazil was established in São Paulo in 1983, with the Instituto Adolfo Lutz appointed for laboratory assistance. Subsequently, research on HIV infections and HIV/HTLV (HIV/HTLV-1 and HIV/HTLV-2) co-infections were conducted. This narrative review focuses on studies from the Immunology Department (1983–2017) that significantly influenced AIDS diagnosis or provided epidemiological data such as prevalence rates, sex, age, and risk factors. Ten studies, encompassing over 8,000 individuals, are discussed. During 1983–1985, nearly all AIDS cases were attributed to homosexual/bisexual men aged 31 years old. Subsequently, heterosexual men and women emerged as risk groups owing to intravenous drug use (IDU) and/or unprotected sexual intercourse with AIDS patients or multiple partners per year. From 1985 onwards, vertical transmission led to child infections. HIV/HTLV co-infection rates decreased over time, initially associated with male IDU, and in the 2010s, with females, IDU, and individuals aged &gt;40 years. Trends in HIV and HIV/HTLV co-infections among younger men and women (&lt;30 years of age) were observed from 2015–2017. The changing characteristics and risk groups for HIV and HIV/HTLV co-infections over the years underscore the necessity for ongoing public policies to prevent retrovirus transmission, particularly among adolescents and young adults.

Urinary tract infections (UTIs) are the second most common bacterial infection with high recurrence rates. A major causative agent of UTIs is uropathogenic Escherichia coli (UPEC), which can form persistent biofilms on urothelial surfaces and/or urinary catheters. Biofilms are inherently tolerant to antimicrobials, making them difficult to eradicate. Ciprofloxacin hybrids functionalised with nitroxides have previously shown enhanced biofilm eradication activity in vitro. Here, we evaluate a ciprofloxacin di-nitroxide hybrid (CDN11), previously reported to have antibiofilm activity against UPEC, as a potential UTI therapeutic in various infection models. We report potent CDN11 activity against mature biofilms formed by cystitis strain UTI89 inside polyethylene catheters. In infected human bladder cell monolayers, CDN11 afforded a 3-log reduction in UPEC colony forming units (CFU) compared to controls, including intracellular bacteria. Infected mouse bladders carrying biofilm-like intracellular UPEC reservoirs had reduced bacterial burdens following treatment with CDN11 ex vivo. Activity trends for CDN11 were comparable throughout all models, indicating that our testing pipeline was robust. New antimicrobial development is arduous and requires large investments of time and money. The pipeline described here could be readily used in testing new compounds, fast tracking the development of novel UTI therapeutics.

Our aim is to provide an insight of the procedures and the dynamics that lead the spread of contagious diseases through populations. Our simulation tool can increase our understanding on the spatial parameters which affect the diffusion of a virus. SIR models are based on the hypothesis that populations are “well mixed”. Our model constitutes an attempt to focus on the effects of the specific distribution of the initially infected individuals through the population and provide insights, considering the stochasticity of the transmission process. For this purpose, we represent the population using a square lattice of nodes. Each node represents an individual that may or may not carry the virus. Nodes that carry the virus can only transfer it to susceptible neighboring nodes. This important revision of the common SIR model provides a very realistic property: the same number of initially infected individuals can lead to multiple paths, depending on their initial distribution in the lattice. This property creates better predictions and probable scenarios to construct a probability function and appropriate confidence intervals. Finally, this structure permits realistic visualizations of the results to understand the procedure of contagion and spread of a disease and the effects of any measures applied.

Urinary tract infections are among the most frequent infectious diseases and require screening of a great amount of urine samples from patients. However, a high percentage of samples results as negative after urine culture plate test (CPT), demanding a simple and fast preliminary technique to screen out the negative samples. We propose a digital holographic microscopy (DHM) method to inspect fresh urine samples flowing in a glass capillary for 3 minutes, recording holograms at 2 frames per second. After digital reconstruction, bacteria, white and red blood cells, epithelial cells and crystals were identified and counted and the samples were classified as negative or positive according to clinical cutoff values. Taking CPT as reference, we processed 180 urine samples and compared the results with those of urine flow cytometry (UFC). Using standard evaluation metrics for our screening test, we found similar performance for DHM and UFC, indicating DHM as a suitable and fast screening technique retaining several advantages. As a benefit of DHM, the technique is label-free and does not require sample preparation. Moreover, the phase and amplitude images of the cells and other particles present in urine are digitally recorded and can serve for further investigation afterwards.

Heart transplantation is a treatment of choice for patients with severe heart failure. Infection transmission from a donor to a recipient remains a prominent problem in organ transplantation. However, the risk of SARS-CoV-2 transmission through nonlung organ transplantation is still unclear. In the article we present a case of a 28-year-old pregnant woman who developed heart failure soon after recovery from SARS-CoV-2 infection in the third trimester of gestation. In the postpartum period the disease worsened and the patient required cardiac transplantation. We examined the recipient's heart and diagnosed left ventricular noncompaction cardiomyopathy. Immunohistochemical analysis showed the SARS-CoV-2 antigen expression in the donor’s heart before transplantation and after the surgery the endomyocardial biopsy was taken. Moreover, an ultrastructural assessment of the endomyocardial specimen revealed endothelial and pericyte injury and single particles on the surface of endothelium consistent with SARS-CoV-2. Recent findings were associated these damages with SARS-CoV-2 infection. The present study describes the rare case of SARS-CoV-2 transmission from donor to recipient through a heart transplant and resulting in endothelial cell and pericyte activation and humoral immune response activation.

Background & aims. The fourth dose of anti-SARS-CoV-2 vaccine slightly improved the humoral response among previously seronegative liver transplant (LT) recipients. Mycophenolate (MMF) treatment worsens the vaccination response. This study aimed to evaluate whether temporary MMF interruption might improve immunogenicity of the fourth anti-SARS-CoV-2 BNT16b2 vaccine dose in nonresponsive LT recipients. Methods. LT recipients negative for anti-spike glycoprotein-specific immunoglobulin G receptor-binding domain (s-RBD) antibodies after the third vaccine dose were enrolled. Anti-SARS-CoV-2 spike-specific T cell responses were measured before and two months following the fourth vaccine dose, and anti-SARS-CoV-2-s-RBD antibodies also 6 months thereafter. MMF was suspended two weeks before and after vaccination. Results. Five LT recipients were enrolled. After a mean of 78 days after vaccination, all patients tested positive for anti-SARS-CoV-2-s-RBD antibodies. The mean antibody titer was 8944 UI/ml. The positive antibody response was maintained during a mean of 193 days of follow-up. Three patients developed a positive T cell response. Two patients (one positive for T cell response) developed a self-limited SARS-CoV-2 infection. Conclusions. Suspending MMF prior to the fourth dose of anti-SARS-CoV-2 mRNA vaccine seems feasible and safe. This procedure could restore vaccine-induced immunogenicity in a large portion of previously nonresponsive LT recipients.

An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. P ≤ 0.05 was con-sidered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From 101 patients that were followed up, smokers had longer treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) is lower than the WHO threshold standard with a high proportion of patients lost to follow-up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.

Macrophage-derived chemokine belongs to the CC subfamily. It is produced by dendritic cells (DCs) and macrophages with or without external stimulation. We have previously shown a statistically significant depletion of MDC/CCL22 concentrations in a number of studies concerning COVID-19. These shifts in concentrations demonstrated stability unrelated to the SARS-CoV-2 genetic variant and remained noticeable even in convalescent patients. In this work, we analyze MDC/CCL22 dynamics in various diseases, including those that manifest with inflammation in lung tissue. In addition, we provide our hypothesis on such a decrease in MDC/CCL22 concentrations in COVID-19. If its secretion by producer cells is unperturbed, then it is possible for viral products to bind to this chemokine and to block its functional activity. There is, however, another possible explanation directly linked to depletion in DC subpopulations and the inhibition of their function. We also discuss MDC/CCL22's role in the immunology of novel coronavirus infection, based on both our own data and other studies.

Background: The objective of the present study was to evaluate the formation of biofilm in bone patellar tendon bone grafts (BPTB grafts) and to compare it to the formation of biofilm formation in quadrupled hamstring anterior cruciate ligament grafts (4xHt graft). Methods: A descriptive in vitro study was conducted. One 4xHt graft and one BPTB graft were prepared. They were then contaminated with a strain of S. epidermidis. Later, a quantitative analysis was carried out by means of microcalorimetry and sonication with plating. Additionally, a qualitative analysis was carried out by means of electron microscopy. Results: No significant differences were found between the bacterial growth profiles of 4xHt graft and BPTB graft in microcalorimetry and colony counting. In the samples analyzed with electron microscopy, no specific biofilm growth pattern was identified upon comparing BPTB graft to 4xHt graft. Conclusions: There were no significant differences at either the quantitative or qualitative level when comparing bacterial growth in BPTB graft to that in 4xHt graft. Therefore, the presence of sutures in 4xHt graft cannot be established as a predisposing factor for increased biofilm growth in this in vitro study.

By using the Sala-i-Martin version of extreme bounds analysis, which is based on the cumulative density function, cross-sectional evidence is presented on the robust determinants of the infection and case mortality rates of Covid-19. The results show that, for most part, different factors determine the infection and mortality rates in developed and developing countries. However, common factors are also apparent, including the risk environment, the number of tests per million and the percentage of population over 65. Notwithstanding the possibility that the official data represent a partial reflection of the truth, it is concluded that the results presented in this study provide useful information that may aid decision-making in the fight against the pandemic.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. Coupled with the increasing burden of healthcare with aging populations and the protracted course the infections may take, these infections contribute to a significant challenge for healthcare. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions is identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents is also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in the near future.

Viruses feature an evolutionary shaped minimal genome that is obligately dependent on the cellular transcription and translation machinery for propagation. To suppress host cell immune responses and ensure efficient replication, viruses employ numerous tactics to favor viral gene expression and protein synthesis. This necessitates a carefully balanced network of virus- and host-encoded components, of which the RNA-based regulatory mechanisms have emerged as particularly interesting albeit insufficiently studied, especially in unicellular organisms. Here, recent advances that further our understanding of RNA-based translation regulation, mainly through post-transcriptional chemical modification of ribonucleosides, codon usage, and (virus-encoded) transfer RNAs, will be discussed in the context of viral infection.

Improving access to sexual health services is critical in light of rising sexually transmitted infections (STIs). We evaluated a Hub and Spoke model for improving access to sexual health services in three general practices in Victoria, Australia. The primary outcome was the impact on HIV and STI (chlamydia, gonorrhoea, syphilis) testing. Segmented linear regression analysis was conducted to examine the trends in the total HIV/STI tests before (from January 2019 to June 2020) and post-implementation (from July 2020 to July 2021). We evaluated the feasibility and acceptability of integrating this model into the general practices using semi-structured individual interviews. There was a statistically significant rise in testing for HIV and STIs in all general practices: post-implementation, there was an increase of an average of 11.2 chlamydia tests per month (p=0.026), 10.5 gonorrhoea tests per month (p=0.001), 4.3 syphilis tests per month (p=0.010), and 5.6 HIV tests per month (p=0.010). Participants reported increases in knowledge level and confidence in offering STI testing and managing more variety of sexual health cases. This study demonstrated the feasibility of implementing a hub and spoke model to enable GPs to deliver sexual health care with support from a sexual health specialist service.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study included all adults with UTI caused by K. pneumoniae admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical and economic data were analyzed. Results: One hundred and seventy-three episodes of UTI caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and time to adequate treatment as risk factors for clinical failure during the first 7 days. Economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean 6,718 € vs 3,688 € respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and time to adequate treatment. Conclusion: UTI caused by ESBL-producing K. pneumoniae requiring hospitalization, and time to adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

In the ongoing Covid-19 pandemic, in the global data on the case fatality ratio and other indices reflecting death rate, there is a consistent downward trend from mid-April to mid-August. The downward trend can be an illusion caused by biases and limitations of data or it could faithfully reflect a declining death rate. A variety of explanations for this trend are possible, but a systematic analysis of the testable predictions of the alternative hypotheses has not yet been attempted. We state six testable alternative hypotheses, analyse their testable predictions using public domain data and evaluate their relative contributions to the downward trend. We show that a decline in the death rate is real; changing age structure of the infected population and evolution of the virus towards reduced virulence are the most supported hypotheses and together contribute to major part of the trend. The testable predictions from other explanations including altered testing efficiency, time lag, improved treatment protocols and herd immunity are not consistently supported, or do not appear to make a major contribution to this trend although they may influence some other patterns of the epidemic.

Coinfections with bacteria or fungi may be a frequent complication of COVID-19, although coinfections with Candida species in COVID-19 patients remain rare. We report the 53-day clinical course of a complicated type-2 diabetes patient diagnosed with COVID-19, who developed bloodstream infections initially due to methicillin-resistant Staphylococcus aureus, secondly to multidrug-resistant Gram-negative bacteria, and lastly to a possibly fatal Candida glabrata. Development of FKS-associated pan-echinocandin resistance in the C. glabrata isolated from the patient after 13 days of caspofungin treatment aggravated the situation. The patient died of septic shock shortly before the prospect of receiving potentially effective antifungal therapy. This case emphasizes the importance of early diagnosis and monitoring for antimicrobial drug-resistant coinfections to reduce their unfavorable outcomes in COVID-19 patients.

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.

Dual-method use is the most reliable form of protection against unintended pregnancies and HIV/STIs. Although dual-method use remains uncommon among women in stable relationships, some women do practice it. In this study, we explored the barriers that make dual-method use rare and the behaviors of women who practice dual-method use using a positive deviance framework in Uganda. We screened 150 women using highly effective contraceptives at five health facilities. We identified nine women who practiced dual-method use and 141 women who did not. In a qualitative study, we conducted in-depth interviews with all nine women practicing dual-method use and 10 women randomly selected out of the 141 who did not. We performed a thematic analysis using the positive deviance framework. Regardless of practicing dual-method use or not, women faced perceived barriers against dual-method use, such as partner’s objection, distrust, shyness about introducing condoms into marital relationships, and limited access to condoms. However, women practicing dual-method use had higher levels of risk perception about unintended pregnancies and HIV/STIs. They also engaged in unique behaviors, such as influencing their partners’ condom use by initiating discussions, educating their partners on sexual risks and condom use, and obtaining condoms by themselves. These findings will be useful in developing effective community-led and peer-based interventions promoting dual-method use to reduce the dual burden of unintended pregnancies and HIV/STIs among women in Uganda.

Background: SARS-CoV-2 has resulted in a global pandemic, COVID-19. The disease has spread outrageously from Wuhan, china to rest of the world affecting millions of people. The human transmission is mainly known to occur by aerosols. As almost every dental procedure is associated with aerosol production, oral health care professionals are at a high risk of getting the infection. An attempt has been made to render cohesive practical suggestions for dental professionals amid COVID-19 outbreak. Objectives: The paper aims at providing evidence based information in managing dental patients during this pandemic. Material and Methods: The paper provides a broad overview of predominant findings based on electronic database search regarding COVID-19 outbreak and its effect on dental practice. Conclusion: Dental care should not be neglected due to the pandemic. Thorough knowledge about the disease and its prevention will not only help us in providing care to these patients but will also help in preventing the nosocomial spread of infection.

Severe COVID-19 is associated with viraemia and multiple organ disease. Similar clinicopathological features have been previously seen in SARS and MERS. Clinically, the severity of SARS, MERS and COVID-19 has been associated with the presence of SARS-CoV, MERS-CoV or SARS-CoV2 viraemia in affected patients. In vitro work has looked at the pattern of viral entry and release from polarised epithelial cells infected by coronaviruses. This work has demonstrated a correlation between the severity of a coronavirus infection and the ability of the virus to reach and infect the basal surface of host cells. It has been postulated that this ability helps the virus invade the bloodstream of the host, resulting in a systemic infection with multiple organ involvement. Here we propose that basal surface release and entry of COVID-19 into and out of cells at epithelial-endothelial interface plays a key pathogenic role in severe COVID-19 disease.

Viral infections are a natural part of our existence. They can affect us in many ways that are the result of the interaction between the viral pathogen and our immune system. Most times the resulting immune response is beneficial for the host. The pathogen gets cleared thus protecting our vital organs with no other consequences. Conversely, the reaction of our immune system against the pathogen can cause organ damage (immunopathology) or lead to autoimmune disease. To date, there are several mechanisms for virus-induced autoimmune disease, including molecular mimicry and bystander activation, in support of the “fertile field” hypothesis, terms defined in our review. On the flip side, viral infections have been associated with protection from autoimmunity through mechanisms that include Treg invigoration and immune deviation, in support of the “hygiene hypothesis”, also defined here. Infection with lymphocytic choriomeningitis virus (LCMV) is one of the prototypes showing that the interaction of our immune system with viruses can either accelerate or prevent autoimmunity. Studies using mouse models of LCMV have helped conceive and establish several concepts that we today know and explain how viruses can lead to autoimmune activation or induce tolerance. Some of the most important mechanisms established during the course LCMV are described in this short review.

Background: Low-income families often depend on fuels such as wood, coal, and animal dung for cooking. Such solid fuels are highly polluting and are a primary source of indoor air pollutants (IAP). We examined the association between solid fuel use (SFU) and acute respiratory infection (ARI) among under-five children in Afghanistan and the extent to which this association varies by socioeconomic status (SES) and gender. Materials and Methods: This is a cross-sectional study based on de-identified data from Afghanistan’s first standard Demographic and Health Survey conducted in 2015. The sample consists of ever-married mothers with under-five children in the household (n=27,565). We used mixed-effect Poisson regression models with robust error variance accounting for clustering to examine the associations between SFU and ARI among under-five children after adjusting for potential confounders. We also investigated potential effect modification by SES and sex. Additional analyses were conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking/kitchen (High Exposure, Moderate, and No Exposure). Results: Around 70% of households reported SFU, whereas the prevalence of ARI was 17.6%. The prevalence of ARI was higher in children living in households with SFU compared to children living in households with no SFU (adjusted prevalence ratio [aPR]= 1.10; 95%CI: 0.98, 1.23). We did not observe any effect modification by SES or child sex. When using the augmented measure of exposure incorporating the kitchen’s location, children highly exposed to IAP had a higher prevalence of ARI compared to unexposed children (aPR 1.17; 95% CI: 1.03, 1.32). SES modified this association with the strongest associations observed among children from the middle wealth quintile. Conclusion: The findings have significant policy implications and suggest that ARI risk in children may be reduced by ensuring clean cookstove as well as clean fuels and acting on the socio-environmental pathways.

Hepatitis-C is one of the most common viral diseases caused by hepatitis C virus (HCV). It is responsible for millions of deaths each year in the developing world. The common dissemination paths of HCV include the use of contaminated water and transfusion of infected blood. Control of this virus has become a challenge for scientists and health professionals due to its versatility and adaptability in different host environments. Along with other problems, lack of efficient diagnosis, quantification and genotyping of viral strains are the major hindrances in a management of this notorious epidemic. The knowledge of HCV genotype and an amount of virus in patient’s blood are pre-requisites to determine the duration and method of treatment. In this review, we discuss the implications of HCV molecular diagnostic methods and their clinical applications. We conclude that while, several commercial and home-brewed methods are available for this purpose, and there is a visible vacuum for cost effective, robust, sensitive assays that can detect multiple viral genotypes in a single reaction. We are of the view that the level of sensitivity offered by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) technique is unequivocal as compared to other techniques. Therefore, researchers may explore further possibilities using this technique in the management of HCV.

The urinary tract infection (UTI) is the most common bacterial infection, especially in women. The increased incidence of UTIs, at the last decades have paralleled with the growing emergence of antibiotic resistance. The aim is to evaluate aqueous garlic extract (AGE) susceptibility against multidrug-resistant (MDR) bacteria isolated in urine of women. The investigation of antibacterial propriety and time kill effect of AGE was performed by the well method, microdilution method and spectrophotometer assay. Antibiotics susceptibility assay revealed that the nine MDR bacteria had high resistance against Amoxicillin/ clavulanic acid (100%) and Erythromycin (100%), Cefotaxime (83.33%) and Ceftazidime (83.33%). AGE exhibited potent antibacterial activity against the nine MDR bacteria tested. In Gram-negative bacteria, the inhibition diameters ranged from 20 ± 3 to 32 ± 4 mm, with Minimum Inhibitory Concentrations (MICs) ranging from 10% to 12.5% (w/v) and Minimum Bactericidal Concentration (MBCs) was 12.5 % (w/v). Gram-positive bacteria exhibited diameters ranging from 38 ± 2 to 45 ± 1 mm; MIC and MBC values ranged from 05 to 10 % (w/v) and were found more susceptible than Gram-negative bacteria. To conclude, this investigation shown that AGE have high potential antibacterial to use as an alternative to treat women UTIs.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

The menace of human papillomavirus (HPV) infections among low- and middle-income countries with no access to free HPV vaccine is a public health concern. HPV is one of the most common Sexually Transmitted Infections (STIs) in Nigeria with high-risk HPV-16 and 18 genotypes. In this study, we explored the predictors of self-reported HPV infections and HPV genital warts infection among a population of students, non-academic staff, and academic staff of Ibrahim Badamasi Babangida (IBB) university located in Lapai, Nigeria. We also assessed their knowledge about HPV infections and genotypes, and sexual behaviors. An online cross-sectional study was conducted by setting up a structured questionnaire on google form and it was distributed to the University community via Facebook and other social media platforms of the university. The form captured questions on HPV infection, knowledge about HPV infection and genotypes, as well as sexual health of the participants. All variables were described using frequencies and percentage distribution, chi-squared test statistics was used to explore the association between HPV infection (medical records of HPV infection) and the participants’ profile, and logistic regression analysis was performed to examine the factors associated with HPV genital warts infection among the population. This study reveals those participants between the ages of 26 – 40 years (81.3%) and those currently not in a union (26.4%) who have self-reported having HPV-16 and -18 genotypes. Also, participants between 26 – 40 years of age (OR: 0.45, 95%CI: 0.22 – 0.89) reported to be carriers of HPV genital warts. Therefore, this study reveals the factors associated with HPV infection and genital warts peculiar to IBB university students and staff. Hence, we suggest the need for HPV awareness programs and free HPV vaccine availability at IBB university.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with documented outcomes in BALB/c mice using identical ocular route and parasite burden (2x105 tachyzoites), with saline as control. Contrary to expectations, Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while survivors showed no apparent signs of infection. Comparative analysis revealed T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while in-fected Swiss albino mice showed enhanced avoidance responses. There was a significant increase in microglial cells in the dentate gyrus molecular layer of infected Swiss albino mice compared to BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses iden-tified three microglial morphological clusters, differentially affected by T. gondii infection across strains. BALB/c mice exhibited increased microglial branching and complexity, while Swiss al-bino mice showed reduced shrunk microglial arbors, diminishing morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory reg-ulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and re-sistance. These elements are critical in devising control measures for toxoplasmosis.

This study aims to explore the associations between pediatric adverse events (PAEs) and hospital and patient characteristics within the inpatient hospital setting, focusing solely on the framework of pediatric quality indicators (PDIs) from the Agency for Healthcare Research and Quality (AHRQ). Specifically, the study focuses on NQI 03 Neonatal Blood Stream Infection (NBSI). The analysis utilizes discharge data from the Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Databases (KID) for the year 2019. Through this analysis, the study seeks to answer research questions regarding associations between hospital characteristics and patient characteristics with NQI 03. The methodology employs bivariate and multivariate logistic regression models to analyze patient-level encounters of NBSI. The results indicate that smaller, rural, and non-teaching hospitals exhibit significantly lower odds of NQI 03 compared to large hospitals. Various individual factors such as gender, age, race, service lines, payment sources, and major operating room procedures also demonstrate differing levels of significance in relation to NQI 03, warranting further investigation. This study provides contextual expansion on the findings and offers valuable insights into PAEs in the inpatient hospital setting, specifically focusing on NBSI within the PDIs framework. It highlights areas for developing evidence-based interventions and guidelines for clinicians and policymakers. Ultimately, the findings contribute to the growing understanding of factors influencing NBSI and emphasize the importance of targeted strategies for improving pediatric patient safety.

Ethanolic extracts of propolis collected from Apis mellifera hives have been shown to reduce Nosema ceranae infection in honey bee workers. This study aimed to determine the propolis concentration that optimizes the control of N. ceranae infection in honey bee workers. Newly emerged worker bees were individually fed 2 μL of 50% sucrose solution (w/v) containing 105 N. ceranae spores per bee, and treated with 0%, 25%, 50%, and 75% ethanolic extracted propolis in 50% sucrose solution (v/v). The treated bees were maintained in cages at 34 ± 2˚C and 55 ± 5% RH throughout the study. The number of dead bees was counted and removed from the cages daily for 30 days to generate survival curves. The number of N. ceranae spores per bee (infectivity) was quantified using a hemocytometer, and the number of infected bees per hundred bees (infection rate) was determined. The survival rates of N. ceranae infected bees fed 25%, 50%, and 75% propolis (NP1, NP2, NP3, respectively) were significantly higher than those of infected bees not fed propolis (NO). Furthermore, the infectivity and infection rates of NP2 and NP3 groups were significantly lower than those of the NO group. The infectivity and infection rates of the NP1 group were not different than those of the NO group. Our data suggest that 50% and 75% propolis extracts are appropriate concentrations for treating N. ceranae infection in honey bees. Ethanolic extracted propolis can be an alternative treatment for N. ceranae infection in Western honey bees.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

From the first isolation of the cystovirus bacteriophage Φ6 from Pseudomonas syringae 50 years ago, we have progressed to a better understanding of the structure and transformations of the many parts of the virion. The three-layered virion encapsulating the tripartite double stranded RNA (dsRNA) genome, breaches the cell envelope on infection, generates its own transcripts, and coopts the bacterial machinery to produce its proteins. The generation of new virions starts with a procapsid with a contracted shape, followed by packaging single stranded RNA segments with concurrent expansion of the capsid, and finally replication to reconstitute the dsRNA genome. The outer two layers are then added, and the fully formed virions released by cell lysis. Most of the procapsid structure composed of the proteins P1, P2, P4 and P7 is now known, as well as its transformations to the mature, packaged nucleocapsid. The outer two layers are less well studied. One additional study investigated the binding of the host protein YajQ to the infecting nucleocapsid, where it enhances the transcription of the large RNA segment that codes for the capsid proteins. Finally, we relate the structural aspects of bacteriophage Φ6 top those of other dsRNA viruses, noting the similarities and differences.

Objectives: To evaluate the relationship between the type of conization, the volume and dimensions of the cone, with the persistence/recurrence of CIN 2-3, presence of affected margins and post-cone HR-HPV positivity. Methods: 227 women treated with LLETZ and histologically confirmed CIN2-3 were evaluated between 1996 and 2006 and followed up until June 2016. Age, type of resection according to IFCPC 2011, volume, cone dimensions, margins were studied. of resection, post-cone high-risk human papillomavirus (HR-HPV) status and viral load. Determinants of HR-HPV positivity were estimated using unconditional logistic regression and time to recurrence was assessed using Kaplan-Meier curves. Results: Persistent/recurrent CIN2-3 was found in 12 cases (5.2%), type 1 conization was performed in 81 patients, with 5 recurrences (6.1%), type 2 in 101 patients, with 6 recurrences (5 .9%) and type 3 resection in 45 women, with 1 recurrence (2.2%). Volume and dimensions were not associated with recurrence. The Log-Rank Test did not show a significant difference between the 3 treatments (p= 0.18). The free margins in type 1 were 37%, in type 2 resection 61% and in type 3 71% (p=0.001). Resection type 1 had 15% HR-HPV post positive cone, type 2 reached 16% and type 3 had 9%, this difference being non-significant (p=0.58). The incidence of recurrence at 36 months in type 1 resection was 0.08%, in type 2 treatment it was 0.04% and in type 3 resection it was 0.0%. Conclusions : Type 3 resection had a higher proportion of free margins and lower post-cone HR-HPV positivity, with a lower incidence of persistence/recurrence.

Recurrent infections after root canal treatments often involve Enterococcus faecalis, a microorganism closely associated with therapy failures due to its biofilm production, survival in nutrient-deprived conditions, and antibiotic tolerance. Essential oils (EOs), which display anti-inflammatory, antimicrobial, and antibacterial properties, exhibit inhibitory effects on the growth of many microorganisms including E. faecalis. This study assessed the in vitro efficacy of combining antibiotics (Gentamicin 1.5mg/ml, Streptomycin 2.5 mg/ml, Ampicillin 5 mg/ml, and Kanamycin 2.5 mg/ml) with Cinnamon (1.25% to 5%) or Clove (25% to 50%) EOs using disk diffusion tests. Disks were treated with EOs-only, antibiotics-only, or EO-antibiotic combinations, placed on BEA agar plates, incubated for 24 hours, and zones of inhibition were measured against E. faecalis. Results showed robust growth inhibition by cinnamon and clove EOs across all tested concentrations. Furthermore, there were synergistic antimicrobial effects when gentamicin, streptomycin and kanamycin were combined with 2.5% and 50% concentrations of cinnamon and clove EOs, respectively, leading to significant growth inhibition of E. faecalis by 139% to 193% compared to using antibiotics or EOs alone. Clove EO showed positive synergism with three antibiotics (gentamicin, streptomycin, and kanamycin) whereas cinnamon EO showed synergism with two antibiotics (streptomycin and kanamycin). These findings suggest that combining cinnamon and clove EOs with aminoglycoside antibiotics can significantly reduce the expansion of E. faecalis compared to antibiotics alone. Further in vivo studies should determine the safety, efficacy, and treatment duration, with the potential to reduce antibiotic dosages and associated toxicity while preventing recurrent infections.

Patients undergoing dialysis through a permanent catheter often experience infection or malfunction. However, few studies have clarified the predictors of permanent catheter patency survival in patients undergoing hemodialysis. We assessed the relationship between parameters of body composition monitoring (BCM) determined before the initiation of dialysis and the patency survival of the permanent catheters inserted in 179 patients who commenced hemodialysis between January 14, 2020 and August 31, 2021. The relationships between permanent catheter patency at 6 weeks and BCM parameters, laboratory tests, age, sex, comorbidities, and medications at baseline were studied using Kaplan–Meier survival curves. Permanent catheter patency was observed to be superior at high extracellular-to-intracellular (ECW/ICW) ratio (P<0.005). After adjustment for covariates, the ECW/ICW ratio remained an independent factor associated with permanent catheter patency survival. When patients with non-patent catheters were subdivided into infection and malfunction groups, and the associations of BCM parameters were evaluated in those groups, the ECW/ICW ratio was not significantly associated with permanent catheter patency survival in the infection group (P = 0.327); instead, a significant association was found for the lean tissue index (P<0.001). In the malfunction group, the ECW/ICW ratio remained significantly associated with permanent catheter patency survival (P < 0.001).

Chronic hepatitis B (CHB) infection and the Hepatitis B virus X protein (HBx) are major risk factors associated with hepatocellular carcinoma (HCC). In CHB infection, HBx induces mitochondrial dysfunction, exhaustion and impaired function in hepatocytes. Restoring hepatocyte health along with reduction in virus replication could be an ideal treatment for CHB. Thiourea derivatives are well known for their antiviral property though their effect on mitochondrial and/ or hepatocyte health remains obscure. This study focus on the repurposing of thiourea derivatives (DSA-00, DSA-02, and DSA-09) on hepatocyte replenishment. HepG2.2.15 cells were treated with thiourea derivatives, alongside Entecavir (ETV). The proteomics analysis showed both DSA-00 and ETV were enriched with proteins associated with antiviral responses. In addition, DSA-00 additionally showed increase in proteins linked to mitochondrial response. Whereas DSA-02 exhibited association with innate immune system and citric acid cycle and DSA-09 displayed pathways similar to DSA-00 and ETV. Treated groups exhibited enhanced bio-energetic and antiviral response as compared to the untreated group. FACS analysis revealed the restoration of exhausted hepatocytes by thiourea derivatives through targeting mitochondria. Our findings suggest that thiourea derivatives hold potential as a novel therapeutic agent that seems to restore mitochondrial health along with anti-viral response in CHB.

More than 3 years have passed since the emergence of COVID-19. On May 8, 2023, COVID-19 in Japan was downgraded to Category 5 by the Infectious Disease Control Law. In Japan, at the beginning of the COVID-19 pandemic in 2020, cases of infection and deaths from severe disease were few compared with those of Western countries. However, in the medical field, screening for COVID-19 was given top priority, resulting in confusion and proving disadvantageous for many patients, also the overreaction to COVID-19 as the most important issue in society can be attributed largely to statements by infectious disease experts. In addition, the mRNA vaccine emerged in 2021, and most of the population was vaccinated up to two times within a short period of less than 1 year because infectious disease experts strongly promoted vaccination. After 2022, when vaccination progressed, and the Omicron strain, which is an attenuated strain, became the mainstay of the SARS-CoV-2, the number of severe cases of COVID-19 decreased significantly; however, the number of infected people increased dramatically instead. A significant portion of the population is thought to have hybrid immunity due to vaccination plus natural infection and maintains high antibody titers. Henceforth, additional vaccination should be given preferentially to those who will benefit most from it. Conversely, measures against COVID-19 caused serious damage to the economy and society. Policies that not only address countermeasures against infection, but also those that encompass the economy and society as a whole are necessary.

Background: Skin and soft tissue infections (SSTI) are common presentations to the emergency department. However, this is less common after contact with contaminated water, both salt or fresh. This review presents the diagnosis and the management of water-related soft tissue sepsis in this vulnerable and difficult to treat subgroup of necrotizing soft tissue sepsis. Methods: A summative literature overview regarding bacterial and fungal SSTI after contact with contaminated water, with practical diagnostic and management aspects addressed. Results: The literature indicates that these remain difficult to treat wounds and organisms. An approach using appropriate diagnostic tools with both medical and surgical management strategies is provided. Conclusion: SSTI due to water contamination of wounds involve unusual organisms with unusual resistance patterns and require a nuanced and directed diagnostic approach with adaptation of the normal antibiotic or antifungal selection to achieve cure, along with aggressive debridement and wound care.

Staphylococci sp. have become the primary pathogens implicated in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations and the protracted course the infections may take, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid’s version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. 35 studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. Ameliorating these molecular pathways may serve as a therapeutic avenue for the prevention and treatment of these infections in near future.

Chorioamnionitis (CA) at term of pregnancy can have infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (Intrauterine Inflammation, Infection or both, TI) has been proposed to reduce the overdiagnosis of infection and the neonatal overtreatment. The aim of the study is to identify clinical and histological variables predicting adverse outcomes when TI has been suspected and/or confirmed. This retrospective cohort study included 404 pregnancies ≥37 g.a. that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to NICHD definition of 2015 and it could be confirmed (TI+) or not (TI-) by histological examination. Signs of infection/inflammation not respecting the definition of TI were classified as “Clinical suspicion”, supported (CS+) or not (CS-) by histology. Histological chorioamnionitis (HCA) without clinical manifestation represented fifth group. Whole Placental Involvement (WPLI), was defined as a histological inflammation involving maternal and fetal side. There were 113 TI+, 30 TI-, 186 CS+, 35 CS- and 40 isolated HCA. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). TI+ compared to CS+ was more predictive of CNO (p=0.001), CMO (p<0.001) and WPLI (p=0.005). WPLI was related both to CNO (p<0.001) and CMO (p=0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p=0.001) and by WPLI (OR 2.23; p=0.001). TI, compared to CS, is a better predictor of CNO and can be useful for the identification of newborns at risk.

Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV in the host. Theoretically, suppression of Treg functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating Mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To determine the efficacy of anti-CHB, 2ug/ml MAF was combined with the GMI-HBVac in an HBV-infected animal model as an anti-Treg treatment. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and upregulation of IFN-gamma producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulates T cell infiltration in HBV-infected liver. These conditions may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF was utilized as an adjuvant to deplete Tregs and paired with GMI-HBVac as a unique therapeutic vaccine regimen against established CHB mice to produce a functional cure, as seen by the remarkable clearance of HBsAg.

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalised patients. Severe SARS-CoV-2 infection is characterized by a proinflammatory state and an associated disbalance in hemostasis. Immune pathology analysis supports the inflammatory nature of pulmonary arterial thrombi composed by white blood cells, especially neutrophils, CD3+ and CD20+ lymphocytes, fibrin, red blood cells and platelets. Immune cells, cytokines, chemokines and the complement system are key drivers of immunothrombosis, as they induce the damage of endothelial cells and initiate pro-inflammatory and pro-coagulant positive feedback loops. Neutrophil extracellular traps induced by COVID-19-associated “cytokine storm”, platelets, red blood cells, and coagulation pathways close the inflammation-endotheliopathy-thrombosis axis, contributing to SARS-CoV-2 associated pulmonary thrombotic events. The hypothesis of immunothrombosis is also supported by the minor role of venous thromboembolism, chest CT imaging data showing peripheral blood clots associated with inflammatory lesions and the high incidence of thrombotic events despite routine thromboprophylaxis. Understanding the complex mechanisms behind COVID-19-induced pulmonary thrombosis will lead to future combination therapies for hospitalised patients with severe disease, that would target the crossroads of inflammatory and coagulation pathways.

Monkeypox virus infection is a recognized public health emergency. Little research has been done on treatment options for this disease. Until recently, there was not a single published work describing the usage of specific drugs in human patients with monkeypox virus infection. This paper gives the first bibliometric analysis of monkeypox treatment options based on data available on PubMed and Scopus. It also reviews the specific drugs used in the treatment of monkeypox. That includes data on Tecovirimat, Cidofovir, Brincidofovir, and Vaccinia Immune Globulin. Tecovirimat is a promising option in progressive disease in terms of efficacy and safety. However, Brincidofovir has been associated with discontinuation of treatment. Cidofovir is also not the preferred drug among physicians. Currently, Tecovirimat can be further used for the management of aggravating cases. More studies should be conducted on Tecovirimat to treat this condition, mainly through controlled trials.

Mutations within the hepatitis B virus (HBV) genome have been associated with rapid progres-sion to hepatocellular carcinoma (HCC); however, there is limited information regarding the prevalence and impact of these mutations in most of sub-Saharan Africa, including Botswana. We aimed to determine the prevalence of HBV mutations known to be associated with progression to HCC using a retrospective, cross-sectional analysis of 48 previously generated HBV sequences from adults with concomitant HBV/HIV initiating HIV antiretroviral therapy in Botswana. The sequences were aligned with reference sequences, and HCC-associated mutations were manually identified using BioEdit. Sixteen (33.3 %) of 48 participant samples had 20 HCC-associated mu-tations. Seven HCC mutations were present in the core region, 4 in the preCore region, 7 in the X region, and one mutation in the surface region, as well as deletions within the preSurface 1 region. Seven of the 16 participants (43.8%) had multiple HCC-associated mutations. There were also previously uncharacterized mutations at positions with known HCC-associated mutations. HCC-associated mutations were common in this cohort; hence, some participants may require close clinical monitoring as they might be more prone to rapid disease progression. Other functionally uncharacterized polymorphisms were also detected and require characterization in future studies.

The scientific, private and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2, including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less obligation mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both the cases of natural infections and post-vaccinations? (iii) Which are the factors responsible for this decay in neutralizing antibodies? (iv) What strategy could be adapted to develop long-term herd immunity? (v) Is the Spike the only vaccine candidate or a vaccine cocktail is better?

Persistent Pain after Spinal Surgery can be successfully addressed by Spinal Cord Stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach. First, it appears that patient outcomes, WITH OR WITHOUT lead trial, are similar. In contrast, during trialing, infection rate drops drastically within time and can compromise the therapy. Using composite pain assessment experience and previous research, we hypothesized that ma-chine learning models could be robust screening tools and reliable predictors of long-term SCS efficacy. We developed several algorithms including logistic regression, Regularized Logistic Regression (RLR), naive Bayes classifier, artificial neural networks, random forest and gradient boosted trees to test this hypothesis and to perform internal and external validations, the objec-tive being to confront model predictions with lead trial results using a 1-year composite out-come from 103 patients. While almost all models have demonstrated superiority on lead trial-ing, the RLR model appears to represent the best compromise between complexity and inter-pretability in prediction of SCS efficacy. These results underscore the need to use AI based-predictive medicine, as a synergistic mathematical approach, aimed at helping implanters to optimize their clinical choices on daily practice.

The interaction of the nervous, immune, and endocrine systems is crucial in the maintenance of homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The aim of the present study was to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice, and the association of these different components with whole parasite counts. We found that parasite load was higher in female in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and Interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes on neuroimmunoendocrine molecules in the spleen during infection. These changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the key role of the neuroimmune network in determining sex-associated susceptibility to the helminth parasite.

To gain new insights into the potential of mother-to-child transmission of Zika virus (ZIKV) through breast milk or breastfeeding practices, we systematically searched regional and international databases and screened 1,658 non-duplicate records describing women with suspected or confirmed ZIKV infection, intending to breastfeed or give breast milk to an infant. Fourteen studies met our inclusion criteria and inform this analysis. These studies reported on 97 mother-children pairs who provided breast milk for ZIKV assessment. Seventeen breast milk samples from different women were found positive for ZIKV via RT-PCR, and ZIKV replication was found in cell cultures from five out of seven breast milk samples from different women. Only three out of six infants who had ZIKV infection were breastfed, no evidence of clinical complications were found to be associated with ZIKV RNA in breast milk. This review updates our previous report by synthesizing the evidence from 12 new articles and we find no evidence of mother-to-child transmission through breast milk intake or breastfeeding. As the certainty of the present evidence is low, additional studies are still warranted to completely understand any potential of transmission of ZIKV through breastfeeding.

Purpose: During the COVID-19 pandemic, the health care workers (HCWs) at the frontline have been largely exposed to infected patients, running an high risk of being infected by the SARS-CoV-2 virus. This study investigates the epidemiological, clinical and lifestyles characteristics that might play roles in the susceptibility of HCWs to COVID-19 in a hit Italian hospital. Methods:Demographic, lifestyle, work-related and comorbidities data of 1447 HCWs which underwent a nasopharyngeal swab for SARS-CoV-2 were retrospectively collected. For the 164 HCWs positive for SARS-CoV-2, data about safety in the workplace, symptoms and clinical course of COVID-19 were also collected. Cumulative incidence of SARS-CoV-2 infection was estimated. Risk factors for SARS-CoV-2 infection were assessed using a multivariable Poisson regression. Results: The cumulative incidence of SARS-CoV-2 infection among the screened HCWs was 11.33 (9.72-13.21). Working in a COVID-19 ward, being a former smoker (vs being a person who never smoked) and BMI were positively associated with SARS-CoV-2 infection, whereas being a current smoker was negatively associated with this variable. Conclusions: Assuming an equal accessibility and proper use of PPE of all the HCWs of our Hospital, the great and more prolonged contact with COVID-19 patients remains the crucial risk factor for SARS-CoV-2. Therefore, increased and particular care needs to be focused specifically on the most exposed HCWs groups, which should be safeguarded. Furthermore, in order to limit the risk of asymptomatic spread of SARS-CoV-2 infection, the HCWs mild symptoms of COVID-19 should be considered when evaluating the potential benefits of universal staff testing

In December 2019, pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection emerged in Wuhan City, Hubei Province, China. Early in 2020, the World Health Organization (WHO) announced a new name for the 2019-nCoV-caused epidemic disease: coronavirus disease 2019 (COVID-19) and declared COVID-19 to be the sixth international public health emergency. Cellular co-infection is a critical determinant of both viral fitness and infection outcome and plays a crucial role in shaping the host immune response to infections. In this study, sixty-eight public next-generation sequencing libraries from SARS-CoV-2 infected patients were retrieved from the NCBI Sequence Read Archive database using SRA-Toolkit. Using an alignment-free method based on K-mer mapping and extension, SARS-CoV-2 was identified in all except three patients. Influenza A H7N9 (3/68), Human immunodeficiency virus 1 (1/68), rhabdovirus isolate (3/68), Human metapneumovirus (1/68), coronaviruses NL63 (1/68), Parvovirus (1/68), Simian virus 40 (1/68), and hepatitis virus (1/68) genome sequences were detected in SARS-CoV-2 infected patients.

Effects of the convection flow, atmospheric diffusivity and humidity on evolution and travel distances of exhaled aerosol clouds by an infected person are considered. The aim of this work is to evaluate the importance of aerosol transmission routes and the effectiveness of the 2-metre separation distance policy. A potential impact of use of face masks on the infection transmission rate, and an opportunity to reduce infection in hospitals, care homes and other public spaces by appropriate monitoring and filtering of air are also considered. The results obtained demonstrate that aerosol particles generated by coughing and sneezing can travel over 30 m. Modelling of the evolution of aerosol clouds generated by coughing and sneezing enables us to evaluate the deposition dose of aerosol particles in healthy individuals. For example, a person in a public place (e.g. supermarket or car park) can accumulate in the respiratory system up to 200 virus copies in 2 min time by breathing in virus laden aerosols. Wearing face mask considerably reduces the deposited load down to 2 virus copies per 2 min. The modelling also suggests that it should be possible to measure virus causing COVID-19 (SARS-CoV-2) within aerosol particles in hospitals and public places, e.g. care homes and supermarkets.

The Coronavirus disease (COVID-19) caused by a novel coronavirus, SARS-CoV-2, has been declared as a global pandemic. Due to its infection rate and severity, it has emerged as one of the major global threats of the current generation. To support the current combat against the disease, this research aims to propose a Machine Learning based pipeline to detect the COVID-19 infection using the lung Computed Tomography scan images (CTI). This implemented pipeline consists of a number of sub-procedures ranging from segmenting the COVID-19 infection to classifying the segmented regions. The initial part of the pipeline implements the segmentation of the COVID-19 affected CTI using Social-Group-Optimization and Kapur’s Entropy thresholding, followed by k-means clustering and morphology-based segmentation. The next part of the pipeline implements feature extraction, selection and fusion to classify the infection. PCA based serial fusion technique is used in fusing the features and the fused feature vector is then employed to train, test and validate four different classifiers namely Random Forest, k-Nearest Neighbors (KNN), Support Vector Machine with Radial Basis Function, and Decision Tree. Experimental results using benchmark datasets show a high accuracy (> 91%) for the morphology-based segmentation task and for the classification task the KNN offers the highest accuracy among the compared classifiers (> 87%). However, this should be noted that this method still awaits clinical validation, and therefore should not be used to clinically diagnose the ongoing COVID-19 infection.

Background & Objectives: The global pandemic caused by novel coronavirus SARS-CoV-2 has claimed several lives worldwide. With the virus gathering rapid spread, the world has witnessed increasing number of confirmed cases and mortality rate, India is not far behind with approximately 37,000 affected individuals as on May 2, 2020. The ongoing pandemic has raised several questions which need to be answered by analysis of transmission of the infection. The data has been collected on daily basis from WHO and other sites. We have represented the data collated graphically using statistical packages, R and other online softwares. The present study provides a holistic overview of the spread of COVID-19 infection in India. Methods: Real-time data query was done based on daily observations using publicly available data from reference websites for COVID-19 and other government official reports for the period (15^th February, 2020 to April 28^th, 2020). Statistical analysis was performed to draw important inferences regarding COVID-19 trend in India. Results: A decrease in growth rate of cases due to COVID-19 in India post lockdown and improvement in recovery rate during the month of April was identified. The case fatality rate was estimated to be 3.22% of the total reported cases. State-wise analysis revealed a deteriorating situation in states of Maharashtra and Gujarat among others as cases continued to increase rapidly there. A positive linear correlation between the number of deaths and total cases and exponential relation between population density and number of cases reported per square km was established. Interpretation & Conclusions: Despite early preventive measures taken up by the Government of India, the increasing number of cases in India is a concern. This study compiles state-wise and district-wise data to report the daily confirmed cases, case fatalities and strategies adopted in the form of case studies. Understanding the transmission spread of SARS-CoV-2 in a diverse and populated country like India will be crucial in assessing the effectiveness of control policies towards the spread of COVID-19 infection.

In the war against the COVID-19 pandemic, the world is experiencing severe resource constraints. Although transmission routes are well understood, we suspect that they cause different disease consequences. We evaluate them in different forms to understand how they affect infection rates and disease severity. In determining how they affect disease outcome, we evaluated target tissue vulnerability, functional role, defense mechanisms, viral concentration, infection vicinity to target vital tissue, and host factors. We found that direct lung infection is the most lethal transmission route followed by bronchi infection. Transmissions by physical contacts, foods, and blood by low viral concentration (as expected in normal human activities) pose lower or much lower risks unless the infection is followed by subsequent lung exposures. After adding transmission route, treatment timings, and improper treatments into the list of known risk factors, we found that death rate and disability rate for young or healthy persons are nearly zero. We show that population based medical model improperly shifts nominal death rate from few vulnerable people to the population resulting in unnecessary population panic, and such panic is responsible for shutting down human activities and the world economy. Finally, we examined limitations in population-based mitigating measures and proposed for governmental and private adoption community guidelines, which are mainly to enable vulnerable people avoid exposures, prevent non-vulnerable people from serving as viral transmitters, get rid of high-risk exposure modes in working environment, improve safety for people in buses, ships and planes, and reduce death and disability rates for infected people.