Needlestick and other sharp injuries (NSIs) are critical occupational hazard for healthcare workers. Exposure to blood and body fluids through NSIs increases the risk of transmission of blood-borne pathogens among them. The objectives of this study were to estimate the one-year incidence of NSIs and investigate its associated factors among the healthcare workers in Saudi Arabia. A cross-sectional online survey was conducted between October and November 2021. A total of 361 healthcare workers participated in the survey from all over Saudi Arabia. The one-year incidence of NSIs among healthcare workers is estimated at 22.2%. More than half of the injury event (53.8%) was not reported to the authority by the healthcare worker. Incidence of NSIs was highest among the physicians (36%) and is followed by nurses (34.8%), dentists (29.2%), and medical technologists (21.1%). The likelihood of injury is higher (OR: 2.51; 95% CI: 1.04, 6.03) among the works aged 26 – 30 years compared to the 20 – 25 years age group and the workers directly deal with needles or other sharp objects while working (OR: 5.90; 2.69, 12.97). The high incidence rate of injury and low reporting rate highlight the needs of an education program targeting healthcare providers with higher risk.

Introduction: Infection of a wound during the thirty days after surgery is considered a surgical site infection (SSI). Because of lack of large studies or documented guidelines for SSI after surgery, we aimed to study risk factors and comorbidities that may lead to SSI.Methods: A cross-sectional study was conducted in one month (May, 2023) included 111 patients. All patients underwent to either abdominal or urological surgeries. Inclusion criteria were: patients aged 18 or older, any type of abdominal or urological open surgery, and no documented history of infection at surgical site infection.Results: we found 24 (21.6 %) patients out of 111 developed SSI after surgery. Male predominance was clear in this study. The number of patients with age 40 years or less was 60 (54 %) and 10 of them developed SSI (14.2 %).Patients who stayed more than 24 hour of preoperative at hospital were less in number than patients who did not (36.9% vs. 63%; p=0.002) respectively. Patients with emergency procedure were 12 patients (10.8 %) in contrast to 99 patients (89.1 %) who underwent a planned surgery (p-value= 0.003). Conclusion: our study revealed a higher incidence of SSI after surgery. Older patients with comorbidities, preoperative stay, emergency surgery, male sex are all correlated to the developing SSI.

Background: The aim of this audit is to evaluate the characteristics of dental infections requiring hospitalisations, which may help improve preventative and management policies. Methods: This study retrospectively evaluated the patients’ records admitted to a public hospital due to dental infections between 2018 and 2019. Results: A total of 102 patients, mostly in thirties with equal gender distribution were admitted with dental infections, presenting with pain (100%), swelling (99%), Trismus (40.2%), dysphagia (27.4%), fever (21%) >37°C, Tachycardia (24.75%) and Tachypnoea (9.3%). Most patients presented (68%) on weekends, outside regular working hours and public holidays. 54 (52.5%) patients had taken prior antibiotics. Dental Caries, smoking, mental health issues and illicit drug use were featured strongly. The majority of patients (56.4%) underwent treatment under local anaesthesia. The total length of hospital stay was 271 days (mean 2.66). Augmentin was the most prescribed antibiotics. Complications were reported in 8.8% patients, primarily related to airway compromise. Conclusion: Dental infections leading to hospitalizations continue to be a burden on the healthcare system. A notable finding was the presentations primarily on weekends, outside regular hours and public holidays and the majority requiring dental intervention under local anaesthesia. Provision of on call emergency dental services may reduce length of hospital stay and admissions.

In this study, we introduce the dynamics of a Hepatitis B virus (HBV) model with the class of asymptomatic carriers and conduct a comprehensive analysis to explore its theoretical aspects and examine the crossover effect within the HBV model. To investigate the crossover behavior of the operators, we divide the study interval into two subintervals. In the first interval, the classical derivative is employed to study the qualitative properties of the proposed system, while in the second interval, we utilize the ABC fractional differential operator. Consequently, the study is initiated using the piecewise Atangana-Baleanu derivative framework for the systems. The HBV model is then analyzed to determine the existence, Hyers-Ulam (HU) stability, and disease-free equilibrium point of the model. Moreover, we showcase the application of an Adams-type predictor-corrector (PC) technique for Atangana-Baleanu derivatives and an extended Adams-Bashforth-Moulton (ABM) method for Caputo derivatives through numerical results. Subsequently, we employ computational methods to numerically solve the models and visually present the obtained outcomes using different fractional-order values. This network is designed to provide more precise information for disease modeling, considering that communities often interact with one another, and the rate of disease spread is influenced by this factor.

Draconian defensive measures have been implemented to combat the COVID-19 pandemic outbreak. These important measures constitute a vital current priority but do little to increase communal immunity and avoid future outbreaks. A longer-term exit strategy for a sustainable return to normalcy has yet to be identified. The development of vaccines or effective therapeutics could largely solve the problem, but their timely development cannot be guaranteed. In this setting, and under the expected societal isolation fatigue from extended social distancing, we here propose the idea that at some point after the outbreak’s peak, hospitals, in addition to providing care for infected people who need it, could also be involved in the development of a controlled exit strategy designed to avoid future outbreaks. We postulate that controlled voluntary deliberate infection in a hospital setting and under continuous and close medical observation may offer a safer alternative compared to random en-masse exposure. We discuss potential risks and benefits, highlighting the need for careful consideration of the associated critical ethical issues.

Catheter-associated bloodstream infection (CVC-BSI) is a significant cause of morbidity and mortality among hemodialysis patients. In our center was a notable increase in CVC associated with patient age and morbidity. This 10-year retrospective study investigated catheter-associated bloodstream infections (CVC-BSI) in hemodialysis patients. We recorded a total of 67 bacteremia episodes in 52 patients, predominantly linked to Gram-positive microorganisms, particularly Staphylococcus aureus, the study found a mean age of 68 years, 74.6% males, and 88% with tun-neled jugular catheters. Notably, catheter removal occurred in 65.7% of cases, more frequently in Gram-positive instances. Two episodes of endocarditis and five ICU admissions were reported. The study identified a higher incidence in the summer and a significant decrease in bacteremia from 2017, coinciding with the introduction of Tauro-LockTM. Despite enhanced preventive measures during the COVID-19 pandemic, there was no significant impact on catheter infection rates. This research emphasizes the importance of early catheter removal, highlights seasonal variations in incidence, and suggests a potential positive influence of Tauro-LockTM on de-creasing CVC-BSI rates in hemodialysis units.

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.

Mucormycosis is an opportunistic fungal infection that is increasingly affecting patients with Coronavirus Disease (COVID-19). This connection is particularly pronounced in specific populations, including individuals with diabetes or those who have recently undergone corticosteroid therapy. Additionally, Cytomegalovirus (CMV) infection is a frequent complication among COVID-19 patients who have previously received corticosteroid or other immune-modulatory treatments. In this case report, we present the clinical details of a 56-year-old male who developed post-COVID pneumonia complicated by both cutaneous mucormycosis and CMV infection.

Acute-on-Chronic Liver Failure (ACLF) refers to the deterioration of liver function in individuals who already have chronic liver disease. In the setting of ACLF, liver damage leads to the failure of other organs and is associated with increased short-term mortality. Optimal medical management of patients with ACLF requires implementing complex treatment strategies, often in an intensive care unit (ICU). Failure of organs other than the liver distinguishes ACLF from other critical illnesses. Although there is growing evidence supporting the current approach of ACLF management, mortality associated with this condition remains unacceptably high. In this review, we discuss considerations for ICU care of patients with ACLF and highlight areas for further research.

Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.

Malaria remains a major public health problem worldwide, with eradication efforts thwarted by drug and insecticide resistance and the lack of a broadly effective malaria vaccine. In continuously exposed communities, polyclonal infections are thought to reduce the risk of severe disease and promote the establishment of asymptomatic infections. We sought to investigate the relationship between the complexity of P. falciparum infection and underlying host adaptive immune responses in an area with high prevalence of asymptomatic parasitaemia in Cameroon. A cross-sectional study of 353 individuals aged 2 to 86 years (median age = 16 years) was conducted in five villages in the Centre Region of Cameroon. Plasmodium falciparum infection was detected by multiplex nested PCR in 316 samples, of which 278 were successfully genotyped. Of these, 60.1% (167/278) were polyclonal infections, the majority (80.2%) of which were from asymptomatic carriers. Host-parasite factors associated with polyclonal infection in the study population included peripheral blood parasite density, participant age and village of residence. The number of parasite clones per infected sample increased significantly with parasite density (r = 0.3912, p<0.0001) but decreased with participant age (r = -0.4860, p<0.0001). Parasitaemia and number of clones per sample correlated negatively with total plasma levels of IgG antibodies to three highly reactive P. falciparum antigens (MSP-1p19, MSP-3 and EBA175) and two soluble antigen extracts (merozoite and mixed stage antigens). Surprisingly, we observed no association between the frequency of polyclonal infection and susceptibility to clinical disease as assessed by the recent occurrence of malarial symptoms or duration since the previous fever episode. Overall, the data indicate that in areas with high perennial transmission of P. falciparum, parasite polyclonality is dependent on underlying host adaptive immune responses, with the majority of polyclonal infections occurring in persons with low levels of protective anti-plasmodial antibodies.

Congenital syphilis still represents a worldwide public health problem. If left untreated, can lead to fetal demise and high neonatal morbidity and mortality. Unfortunately, in the last decade there has been a resurgence of cases in the US. This review discusses the ongoing problem of this preventable congenital infection, vertical transmission and clinical manifestations while providing a guidance for the evaluation and management of infants born to mothers with reactive serologic tests for syphilis

OBJECTIVE A quality improvement study to assess catheter-associated urinary tract infection (CAUTI) rate post-implementation of a bladder catheter with integrated active drain line urine clearance and automated intra-abdominal pressure monitoring in a burn intensive care unit (ICU). DESIGN Eight-year retrospective before and after study (2015–2022). SETTING A single American Burn Association verified Burn Center with fourteen inpatient beds. PATIENTS Patients meeting criteria for admission to a Burn Center METHODS Retrospective cohort study following the implementation of a novel urine output monitoring system with integrated drain line and urine clearance. Data from a 48-month (from January 2015-December 2018) historical control (period 1) were compared to data from a 28-month (from January 2020 to April 2022) post-implementation period (period 2). Pre- and post-implementation CAUTI event incidences were compared. Charts were reviewed to characterize the patients. RESULTS A total of 42 CAUTIs in 2243 patients were identified using the National Health and Safety Network (NHSN) definition during the analyzed period. There were 40 CAUTI events in period 1 and two CAUTIs in period 2. The incidence of CAUTI events pre-implementation was 0.030 (mean of 10 CAUTI events per year) compared to 0.002 (mean of 1 CAUTI event per year) post-implementation of an automatic drain line clearing UO monitoring system showing a significant reduction in CAUTI events (P<0.01, risk ratio novel vs. gravity bladder catheter 0.071, 95% confidence interval: 0.017-0.294). CONCLUSIONS CAUTIs were reduced in the period following the implementation of a novel urinary catheter system with an integrated active drain line and urine clearance in burn patients.

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.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.

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 febrile patient from tropical areas, in which emerging arboviruses are endemic, represent a diagnostic challenge and potential co-infections with other pathogens (i.e bacteria or parasites) are usually overlooked. Objectives: We present a case of an elderly woman diagnosed with dengue, chikungunya and Leptospira interrogans co-infection. Study Design: Case report. Results: An 87-year old woman from Colombia complained of upper abdominal pain, arthralgia, myalgia, hyporexia, malaise and intermittent fever accompanied with progressive jaundice. She had a medical history of chronic heart failure (Stage C, NYHA III), without documented cardiac murmurs, right bundle branch block, non-valvular atrial fibrillation, hypertension, and chronic venous disease. Her cardiac and pulmonary status quickly deteriorated after 24 hours of her admission without electrocardiographic changes and she required ventilatory and vasopressor support. In the next hours the patient evolved to pulseless electrical activity and then she died. Dengue IgM, NS1 ELISA, MAT for Leptospira interrogans and RT-PCR for chikungunya, were positive. Discussion: This case illustrates a multiple co-infection in a febrile patient from a tropical area of Latin America that evolved to death.

There is a rising global concern for the ongoing outbreak of SARS-CoV-2 due to its high transmission rate and unavailability of treatment. Through the binding of its spike glycoprotein with angiotensin type 2 (ACE2), SARS-CoV-2 can efficiently get in the cells of patients and start its pandemic cycle. Herein, the biological diversity of SARS-CoV-2 infection was assessed in Babylon province of Iraq by investigating the possible genetic variations of the spike glycoprotein. A specific coding region of 795 bp within the viral spike (S) gene was amplified from 19 patients who suffered from obvious symptoms of SARS-CoV-2 infection. Sequencing results identified fifteen novel nucleic acid variations with a variety of distributions within the investigated samples. The electropherograms of all the identified variations showed obvious co-infections with at least two different viral strains per sample. Within these co-infections, the majority of samples exhibited three nonsense single nucleotide polymorphism (SNP)s, p.301Cdel, p.380Ydel, and p.436del, which yielded three truncated SARS-CoV-2 spike glycoproteins of 301, 380, and 436 amino acids length, respectively. The network and phylogenetic analyses indicated that for all viral infections were derived from multi-ancestral origins. Results inferred from the specific clade-based tree entailed that some viral strains were derived from European G-clade sequences. In conclusion, our data demonstrated the absence of any single strain infection among all investigated viral samples in the studied area, which may entail a higher risk of SARS-CoV-2 in this country. Through the identified high frequency of truncated spike proteins, we suggest that defective SARS-CoV-2 may depend on helper strains having intact spikes in its infection. Alternatively, another putative ACE2-independent route of viral infection way also suggested. To the best of our knowledge, this is the first report to describe the co-infection of multiple strains of SARS-CoV-2 in patients with COVID-19.

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. A total of 117 patients (n=117 eyes) with FK were included in this study. The mean age was 59.0±19.6 years (range, 4-92 years) and 51.3% patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9±16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67±1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3mm), and poor presenting CDVA (<1.0 logMAR) as significant negative predictive factors for poor visual outcome (CDVA of <1.0 logMAR) and poor corneal healing (>60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p<0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcome, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need.

Dengue is an overlooked tropical disease for which billions of people are at risk. The disease, caused by a Flavivirus with four distinct serotypes, is transmitted primarily by urbanized Aedes mosquito species. The infection leads to a spectrum of clinical manifestations, with the majority being asymptomatic. Primary dengue and, to a greater extent, subsequent infection, mainly secondary dengue infection, are associated with increased severity. Increased global travel and recreational tourism expose naïve individuals to dengue, the most common arboviral infections in travelers. We describe a cluster of possible primary acute dengue infections in a group of 12 individuals who presented to Bangkok Hospital for Tropical Diseases in 2017. Infection was confirmed by dengue NS1 antigen and multiplex real-time RT-PCR. Nine individuals required hospitalization, and four developed dengue warning signs. The mean arterial pressure was significantly lower in the group with dengue warning signs. The period from the day of arrival in Thailand and the first day of symptoms was significantly shorter in adolescents with warning signs. Leukocytes, neutrophils, and platelets declined significantly at defervescence and were negatively correlated with day of illness. Six clinical isolates were identified as dengue serotype-1, with identical sequences suggesting that these patients were infected with the same virus.

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We asses s the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.

Odontogenic infections are infections of the orofacial structures arising from dental disease. Despite its preventability, it exerts a significant burden on healthcare infrastructure worldwide. Our study explored the various different microbiological, social, and epidemiological characteristics of 103 cases of odontogenic infections at our regional center which demonstrated specific predilections for the young and middle-aged, those with diabetes mellitus, African American/Black and Hispanic ethnicities, posterior teeth, left-sided dentition, and male gender. However, nuances and exceptions to these trends were also seen with specific groups that may complicate treatment.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: The aim of our study was to analyze the effect of socioeconomic inequalities, both at the individual and area of residence levels, on the probability of COVID-19 confirmed infection, and its variations across three pandemic waves. Methods: Retrospective cohort study. We included data from all individuals tested by COVID-19 during the three waves of the pandemic, from March to December 2020 (357,989 individuals). We studied the effect of inequalities on the risk of having a COVID-19 confirmed diagnosis after being tested using multilevel analyses with two levels of aggregation: individuals and basic healthcare area (BHA) of residence (deprivation level and type of zone). Results: Patient profile changed through the pandemic, with a predominance of low-paid employees living in deprived BHA. Workers with low salaries, unemployed and people on minimum integration income or who no longer receive the unemployment allowance, had a higher probability of COVID-19 infection than workers with salaries ≥€18,000 per year. Inequalities were higher in women and in the second wave. The deprivation level of BHA of residence influenced the risk of COVID-19 infection, especially in the second wave. Conclusions: There are inequalities in the risk of COVID-19 confirmed infection, both at individual and area level. It is necessary to develop individual and area coordinated measures in the control, diagnosis and treatment of the epidemic, in order to avoid an increase in the already existing inequalities.

Background: Platelets are increasingly recognised for their multifaceted roles in inflammation beyond their traditional involvement in haemostasis. This review consolidates knowledge on platelets as critical players in inflammatory responses. Methods: This study did an extensive search of electronic databases and identified studies on platelets in inflammation, focusing on molecular mechanisms, cell interactions, and clinical implications, emphasising recent publications. Results: Platelets contribute to inflammation via surface receptors, release of mediators, and participation in neutrophil extracellular trap formation. They are implicated in diseases like atherosclerosis, rheumatoid arthritis, and sepsis, highlighting their interaction with immune cells as pivotal in the onset and resolution of inflammation. Conclusion: Platelets are central to regulating inflammation, offering new therapeutic targets for inflammatory diseases. Future research should explore specific molecular pathways of platelets in inflammation for therapeutic intervention.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

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.

This article explores the knowledge about preventions, perceptions of infections, and the responsive actions to the Covid-19 situation of the young age groups residing in Bangladesh. Quantitative data were collected online using an MCQ questionnaire from around 932 participants. Results show the population is generally aware of the symptoms, keeping social distance by staying home and are concerned about re-spreading after the lock-down period. However, they are quite unsure about the possible medicines frequently talked about in the media and the necessity of avoiding animal protein.

Zika virus (ZIKV) is transmitted to humans by the infectious bite of mosquitoes like Aedes aegypti. After a viremic blood meal, the virus must infect the midgut, disseminate to tissues, and reach the salivary gland to be transmitted to a vertebrate host. Many factors influence the mosquito’s ability to become infected and transmit viruses, such as the mosquito’s genetic diversity, intrinsic antiviral barriers, and midgut microbiota. This study evaluated the patterns of ZIKV infection in Ae. aegypti field populations of a city. The infection rate, disseminated infection rate, viral transmission rate, and transmission efficiency were measured by quantitative PCR at 14 days post-infection. The results showed that all Ae. aegypti populations had individuals susceptible to ZIKV infection and able to transmit the virus. The infection parameters showed the city’s geographical area of origin of the Ae. aegypti influences their vector competence for ZIKV transmission.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here we aim to shed light on the importance of antibody titers and epitope utilization in protection from re-infection. Health care workers are highly exposed to COVID-19 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titers against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N=300) during the second wave of the pandemic were identified by assessing the IgG anti-N titers before and after the second wave. We assessed epitope coverage and antibody titers between the 'single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p=0.019) and IgA (p=0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p=0.004) and anti-S titers (p=0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic.

Background. Candida bloodstream infections (CBSIs) have decreased among pediatric populations in the United States, but remain an important cause of morbidity and mortality. Species distributions and susceptibility patterns of CBSI isolates diverge widely between children and adults. Awareness of these patterns can inform clinical decision-making for empiric or pre-emptive therapy of children at risk for candidemia. Methods. CBSIs occurring from 2006-2016 among patients in a large children’s hospital were analyzed for age specific trends in incidence rate, risk factors for breakthrough-CBSI and death, as well as underlying conditions. Candida species distributions and susceptibility patterns were evaluated in addition to antifungal agent use. Results. The overall incidence rate of CBSI among this complex patient population was 1.97/1,000 patient-days. About half of CBSI episodes occurred in immunocompetent children and 14% in Neonatal Intensive Care Unit (NICU) patients. Antifungal resistance was minimal: 96.7% of isolates were fluconazole-, 99% were micafungin-, and all were amphotericin susceptible. Liposomal amphotericin was the most commonly prescribed antifungal agent including for NICU patients. Overall CBSI-associated mortality was 13.7%; there were no deaths associated with CBSI among NICU patients after 2011. Conclusions. Pediatric CBSI characteristics differ substantially from those in adults. Improved management of underlying diseases and antimicrobial stewardship may further decrease morbidity and mortality from CBSI while continuing to maintain low resistance rates among Candida isolates.

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.

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.

In the present work we propose a dynamical mathematical model of the lung cells inflammation process in response to SARS-CoV-2 infection. In this scenario the main protease Nsp5 enhances the inflammatory process, increasing the levels of NF kB, IL-6, Cox2, and PGE2 with respect to a reference state without the virus. In presence of the virus the translation rates of NF kB and IkB arise to a high constant value, and when the translation rate of IL-6 also increases above the threshold value of 7 pg mL^-1 s^-1 the model predicts a persistent over stimulated immune state with high levels of the cytokine IL-6. Our model shows how such over stimulated immune state becomes autonomous of the signals from other immune cells such as macrophages and lymphocytes, and does not shut down by itself. We also show that in the context of the dynamical model presented here, Dexamethasone or Nimesulide have little effect on such inflammation state of the infected lung cell, and the only form to suppress it is with the inhibition of the activity of the viral protein Nsp5.To that end, our model suggest that drugs like Saquinavir may be useful. In this form, our model suggests that Nsp5 is effectively a central node underlying the severe acute lung inflammation during SARS-CoV-2 infection. The persistent production of IL-6 by lung cells can be one of the causes of the cytokine storm observed in critical patients with COVID19. Nsp5 seems to be the switch to start inflammation, the consequent overproduction of the ACE2 receptor, and an important underlying cause of the most severe cases of COVID19.

Improvement in medical care has turned severe diseases into chronic conditions, but often their treatment and use of medical devices are related to specific complications. Here we present a clinical case of a long-term dialysis patient, who is infected with a rare opportunistic infectious agent – Gordonia sputi. In recent years the incidence of Gordonia spp. infections in immunocompromised patients with central venous catheters (CVC) appear to rise. Their isolation and identification are challenging and require modern techniques. In addition, the treatment is usually persistent and often results in CVC extraction, which is associated with further risk and costs for the patient. We also studied the alternations in the immune status of the patient caused by long-term renal replacement therapy and persistent HCV infection. Antibiotic therapy and immunostimulation with Inosine pranobex lead to successful eradication of the infection without the need for CVC replacement.

Background The acknowledgment of computed tomography (CT) defined diagnosis in high prevalence northern Italy may identify more patients with Coronavirus Disease-2019 (COVID 19) infection, than RT-PCR alone. Methods We retrospectively reviewed 148 chest CT scans of oncological patients who were referred to the Radiological Unit of Policlinico S. Marco from 1st of February 2020 to 30th of April 2020, during the Covid-19 outbreak in Bergamo area. Therefore, we analyzed RT-PCR tests of these 148 patients. Results Among 32 patients with diagnosis of COVID-19 infection: 17 patients were asymptomatic or had mild symptoms (53.1%), while 15 developed severe disease (46.8%). The incidence of COVID-19 infection is 22.9%, the mortality rate is 18.8%. Severe COVID-19 disease is associated with higher median age. We did not find any correlation between disease severity and sex, smoke or cardiovascular comorbidities. Remarkably, patients who were on treatment developed milder disease than cancer patients who were not on treatment. Conclusions The acceptance of CT-defined diagnosis in high prevalence area like Bergamo highlighted a larger number of COVID-19 oncological population than RT-PCR alone, in particular asymptomatic and mild symptomatic patients. We observed that actively treated patients had milder disease, according to previous studies that suggested a protective role of immunosuppression.

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?

Abstract: Background: The birthrate of Black preterm (BPT) infant is 65% higher than White preterm (WPT) infants with BPT mortality 2.3 times higher. The incidence of culture positive sepsis is as high as 41% in preterms. This study aimed to examine infections and mortality in BPTs and WPTs. Methods: We enrolled 362 preterms born < 32 weeks gestational age (GA) between 2019-2023 in 5 neonatal intensive care unit (NICU)s to study onset of infections, and dispositions; RedCap data were analyzed for descriptive statistics. Results: 226 BPTs (63.5%) and 107 WPTs (30.8%) enrolled, with 29 other than White or Black, 50.5% female, mean GA of 27.67 weeks and 986.74 grams birthweight. Of 426 suspected infections evaluated in enrolled infants, there were 7 infants with early onset sepsis (EOS) and 39 infants with late onset sepsis (LOS). The incidence of EOS was 1.9% overall, 2.2% in BPTs vs 0.9% in WPTs. LOS incidence was 10.8% overall, 11.9% in BPTs and 9.3% in WPTs. Both BPT and WPT infants had ~ 8% gram-positive LOS events and 3% gram-negative LOS events; however, 82% of all gram-negative LOS episodes occurred in BPTs. There were 27 urinary tract infections and 78% were in BPTs. Two cerebral spinal fluid cultures were positive in BPTs. Necrotizing enterocolitis was diagnosed in 5.8% of the sample, with an incidence of 6.1% in BPTs versus 4.7% in WPTs. Death occurred in 6.0% of the enrolled infants with the rate of death being slightly higher in BPTs (7.0%) versus WPTs (5.6%). Conclusions: BPTs had a higher rate of positive cultures, double the gram-negative infections, a much higher rate of urinary tract infec-tions and a higher rate of mortality than their WPT counterparts. This study emphasizes higher risk of morbidity and mortality for BPTs.

Tinea incognito is a kind of skin infection that is caused by a fungus which has been changed by the use of topical or systemic steroids or other immunosuppressive medications. This alteration in the typical clinical presentation of the infection makes it difficult to diagnose for general practitioners and dermatologists. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. This condition can affect individuals of all ages and genders, but it is more common in children. Tinea incognito is a type of fungal skin infection that can present with various and non-specific clinical features, such as sudden onset of itching in an area that was previously unaffected, making it challenging to differentiate from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves stopping the use of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for suspecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures. The therapy utilized in published studies is also reviewed.

Presenting a case report on the occurrence of IgA nephropathy with hepatitis B infection in a 32-year-old male patient with main complaints of generalized weakness, easy fatigue, and bilateral swelling of the lower extremities. IgA nephropathy (IgAN), or Berger’s disease, is the most common primary glomerulonephritis worldwide. It is characterized by the formation of IgA1-containing circulating immune complexes and their deposition in the glomerular mesangium. Its etiology remains multifactorial and often idiopathic. IgA nephropathy alone does not have an infectious etiology; instead, it usually develops in conjunction with an infectious condition that triggers a dysregulated immune response. There is no proof that any particular infectious agent is the secondary cause of IgA nephropathy. Hepatitis B virus (HBV) infection is an infectious agent associated with renal complications, including IgA nephropathy. Symptoms include gross haematuria and mild proteinuria indicative of renal involvement. Laboratory investigations and serological tests are followed by imaging studies such as ultrasound and renal biopsy to confirm the diagnosis. The challenges encountered during the diagnostic process included overlapping symptoms and limitations of available diagnostic tests, highlighting the need for comprehensive diagnostic evaluation and multidisciplinary management approaches in similar cases. This case underscores the importance of recognizing and managing both conditions simultaneously to prevent long-term complications such as end-stage renal disease.

Young people living with perinatal infections of Human Immunodeficiency Virus (YLPHIV) face a chronic disease, with treatment including adherence to life-long antiretroviral treatment (ART). The aim of this QES was to explore adherence to ART for YLPHIV as an assemblage within the framework of the BPS model with a new materialist perspective. We searched up to November 2021 and followed the ENTREQ and Cochrane guidelines for QES. All screening, data extraction and critical appraisal was done in duplicate. We analysed and interpreted the findings innovatively, by creating images of meaning, a storyboard, and storylines. We then reported the findings in a narrative first person story. We included 47 studies and identified 9 storylines. We found that treatment adherence has less to do with humans’ preferences, motivations, needs and dispositions, and more to do with how bodies, viruses, things, ideas, institutions, environments, social processes, and social structures assemble. This QES highlights that adherence to ART for YLPHIV is a multisensorial experience in a multi agentic world. Future research into rethinking the linear and casual inferences we are accustomed too in evidence-based health care is needed if we are to adopt multidisciplinary approaches to address pressing issues such as adherence to ART.

Background: Coronavirus Disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/ml. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33^rd day of hospitalization. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Hospital-acquired infections (HAIs) contribute to increased length of hospital stay, high mortality and higher health-care costs. Prevention and control of HAIs is a critical public health concern. We conducted a cross-sectional survey of 213 hospital health-care workers in Qassim, Saudi Arabia. We assessed Knowledge, Attitude and Practice (KAP) of standard infection control precautions using a structured questionnaire. Predictors of KAP were investigated using multivaraible logistic regression analyses and independent sample t tests. Prevalence of good (≥80% correct response) knowledge, attitude and practice were 67.6%, 61.5% and 73.2%, respectively. Predictors of good knowledge included age over 34 years (adjusted odds ratio: 30.5, p<0.001), and receiving training (13.3, p<0.001). Predictor of positive attitude was having >6 years of experience (5.5, p<0.001). While, the predictors of good practice were having >6 years of experience (2.9, p<0.01), previous exposure to HAIs (2.5, p<0.05) and training (3.5, p<0.01). However, being female (0.22, p<0.001) and older (>34 years) (0.34, p<0.01) were negatively associated with knowledge. Results indicate that older academic programs might not have adequately covered infection crontrol. Arranging training for HCWs might be useful in improving their knowledge of standard infection control precautions and is also expected to facilitate positive attitude and practice.

In this article we have presented a new perception of herd immunity threshold (HIT) which considers that only a “band of population” are susceptible to any pathogenic infection. This is termed as the “effective herd immunity threshold” (EHIT) and the progression of the disease (caused by this pathogenic infection) is mainly determined by this EHIT value. We have argued here that this EHIT value (considering the immunity band picture in the population) will be substantially lower than the estimated canonical HIT values obtained from various existing models. We propose that the actual prediction of the disease progression should now be calculated using the EHIT values.

Background: Community acquired Acinetobacter pneumonia (CAAP) typically presents with rapid progression to fulminant disease, and is complicated by high mortality. Australian epidemiological studies are few. Methods: We conducted a retrospective study on bacteraemic cases of CAAP over twenty years, (2000-2019) in North Queensland. Cases were selected on microbiologic, clinical, and radiographic parameters. Data on patient demographics were obtained, along with microbial, antibiotic, mortality, and climatic data. Results: 28 cases of CAAP were included. Nineteen (67.9%) were male, twenty-three (82.1%) were Indigenous Australians, and mean age was 45.9 years. Most presentations were of moderate to severe pneumonia, 25/28 (89.3%). 90% of cases had two or more risk factors. The strongest risk factors for CAAP were alcohol excess and tobacco use. No statistically significant difference in presenting severity, ICU admission or mortality was seen between dry and wet season disease. Dry season disease accounted for 35.7% of cases. Overall mortality was 28.6%. Early use of meropenem or gentamicin reduced mortality irrespective of presenting severity (mortality 17.6%) Non-targeted antibiotic therapy was associated with a non-significant difference in mortality of 44.4%. Conclusions: Early administration of targeted antibiotics can mitigate a high mortality rate. Choice of antibiotic therapy for community acquired pneumonia should be based upon severity, risk factors and clinical suspicion of CAAP rather than seasonality.

INTRODUCTION: Superficial cutaneous bacterial infections have a high incidence in geriatric patients. The most implicated pathogens are gram-positive cocci (Staphylococcus aureus, Streptococcus pyogenes) while gram-negative germs are also implicated. Resistances to common topical antibiotics (mupirocin, fusidic acid) require alternatives to gram-positive and gram-negative microorganisms.Ozenoxacin cream for topical use (non-fluorinated bactericidal quinolone), in other countries and with other galenics, is indicated in children older than 6 months and in adults as a treatment of superficial bacterial infections, such as acne. In Spain, ozenoxacin cream is indicated only for non-bullous impetigo; scientific evidence show effectiveness also in other superficial skin bacterial infections.A cases series of clinical use of ozenoxacin in bacterial superficial skin infections in geriatric patients (institutionalized or community dwelling) is presented.METHODS: Multicenter case series (March-August 2022) of bacterial superficial skin infections treated with ozenoxacin cream (10mg/g every 12h, 5days); data from medical records (controls: 1-3-5 days), after obtaining informed consent (use of data and images).RESULTS: Series of 28 patients (mean age: 84,79) from nine nursing homes and one outpatient geriatric service, including acute and subacute/chronic cases.In all cases treatment was ozenoxacin 10mg/g topical cream applied every 12 hours for 5 days according to medical prescription (except for one case in which 3 days were enough for complete healing and another case treated for 10 days).Results showed complete healing in all 20 acute cases and significant clinical improvement in all subacute/chronic cases (with complete healing in one of them). Professionals scored the effectiveness in acute cases as a mean 4.5 points (maximum score: 5, p<.0001) and in subacute/chronic cases as 3.8 points (p=.010).There was no skin irritation or other adverse effects in anyone of the patients, and clinical improvement of pain, itching and other symptoms was observed, suggesting an anti-inflammatory effect. DISCUSSION AND CONCLUSIONS: Our results seem to demonstrate the effectiveness and tolerability of ozenozacin cream in bacterial infections other than non-bullous impetigo. Ozenoxacin cream is indicated only for the treatment of non-bullous impetigo; however, it is also shown to be effective, both in the scientific evidence and in our case series, for other superficial bacterial skin infections, both acute and subacute/chronic, suggesting the opportunity for clinical studies with an experimental design to evaluate the findings of clinical practice and to be able to have a therapeutic alternative to compensate for the complications of the appearance of resistance.

We hypothesized that biofilm production occurs on stainless steel when incubated with tissue specimens in thioglycolate broth media (TBM). In a diabetic foot infection (DFI) cohort, applying the Kirschner wire and conventional methods were more sensitive than applying only the latter (CI 90%; 0.167 versus 0.375).

Objective: Urinary catheters are known cause of urinary morbidities. The longer the catheter is retained, the greater the risk for contamination and infection. An increasing body of literature suggests routine practice of catheterization and retaining it for 24 hours does not add any procedural advantage. Thus, we sought to study outcomes in relation to early vs. delayed removal of urinary catheters following cesarean section. Methods: We randomly assigned 116 patients into early and delayed removal of urinary catheter groups. In the early group, catheter was removed immediately after the procedure and in the delayed removal group, catheter was removed 24 hours later. Clinical outcomes were measured in terms of significant bacteriuria 72 hours postop, voiding difficulties, urinary retention, mobilization time, length of hospital stay, and patient satisfaction. Results: Study revealed higher incidence of bacteriuria in the delayed removal group (32.8% vs. 15.5%, P = 0.030). Urinary frequency was also higher (34.6% Vs. 8.6%, P=0.001). However, there were no difference between the two groups in other urinary complaints including dysuria and urgency (P = 0.103 & P = 0.087). Urinary retention was more frequent in the early group, but difference was not significant (P = 0.080). Patients with immediate removal of the urinary catheter had early ambulation and early discharge from hospital (P = 0.001 and P = 0.040) and were generally satisfied with the procedure (P= 0.010). Conclusion: Our study showed that immediate removal of urinary catheter was associated with lower urinary complications, shorter length of hospitalization and associated cost.

We performed an epi and molecular characterization of two healthcare workers MPXV occupational infection. Five days after the sampling collection, nurses developed typical MPXV infection symptoms. Infection was confirmed by qPCR and whole genome sequencing. The most likely transmission route was through contact with fomites in the patient belonging/house.

The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments and vulnerable biological status. We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022. The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases. In conclusion, the co-infection of COVID-19 had an impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.

Background: Hospital-acquired infections (HAI) pose a significant danger to global public health, mainly because their numbers are growing exponentially each year. Additionally, the rise of bacterial strains resistant to current treatment options further exacerbates this threat. The study aimed to examine the occurrences of HAIs identified in public hospitals at the county level. Methods: We conducted a cross-sectional study utilizing data provided to the Mures Public Health Directorate from all the public hospitals within this county. We examined HAIs reported during the period spanning from 2017 to 2021, which amounted to a total of 4603 cases. Results: The medical departments reported the highest prevalence of HAIs at 48.25%. The most common infections in-cluded enterocolitis with Clostridioides difficile (32.61%), COVID-19 (19.83%), bronchopneumonia (16.90%), sepsis, surgical wound infections, and urinary tract infections. The five most frequently identified pathogens were Clostridioides difficile (32.61%), SARS-CoV-2 (19.83%), Acinetobacter baumannii (11.82%), Klebsiella pneumoniae (9.58%), and Pseudomonas aeruginosa (7.95%). Acinetobacter baumannii was the predominant agent causing bronchopneumonia, while Klebsiella pneumoniae was the leading cause of sepsis cases. Escherichia coli was the primary agent behind urinary tract infec-tions, and Staphylococcus aureus MRSA was identified as the main etiology for wound infections and central catheter infections. Throughout the study period, there was a significant rise in Clostridioides difficile cases, accounting for 40.36% of all reported HAIs in 2021. Conclusions: The study identifies Clostridioides difficile increase in HAI cases during COVID-19, highlighting the need for careful antibiotic use, and emphasizing the growing challenge of multi-resistant strains in post-pandemic state hospitals.

By providing useful tools to study host-pathogen interactions, next-generation omics has recently enabled the study of gene expression changes in both pathogen and infected host simultaneously. However, since great discriminative power is required to study pathogen and host simultaneously throughout the infection process, the depth of quantitative gene expression profiling has proven to be unsatisfactory when focusing on bacterial pathogens, thus preferentially requiring specific strategies or the development of novel methodologies based on complementary omics approaches. In this review, we focus on the difficulties encountered when making use of omics approaches to study bacterial pathogenesis. Besides, we review different omics strategies (i.e. transcriptomics, proteomics and secretomics) and their applications for studying interactions of pathogens with their host.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Saliva, as a diagnostic medium, offers a promising alternative to blood by virtue of its non-invasive collection, which enhances patient compliance, especially in paediatric and geriatric populations. In this study, we assessed the utility of saliva as a non-invasive medium for measuring V. cholerae-specific serum antibodies in naturally infected individuals. We tested paired serum and saliva samples obtained from a total of 63 cholera patients enrolled in a cohort study. Vibriocidal antibodies assay (IgM/IgG) as markers for accurate determination was used to determine cholera specific antibody levels. Using receiver operating characteristics (ROC) curve, we found that the best cut-off that maximizes (sensitivity + specificity) is 10 titers. At this saliva titer, the sensitivity is 76.9% (95%CI: 60.9%, 87.7%) and specificity is 80.0% (95%CI: 56.6%, 92.5%). Using Spearman’s correlation coefficient, we also found evidence of a positive correlation between Vibrio Cholerae saliva and serum antibodies (rho=0.66, p&lt;0.001). In conclusion, saliva-based diagnostic cholera tests has high diagnostic accuracy, and would be advantageous, cheaper, and quicker for early diagnosis of severe cholera outcomes.

Background: On late December 2019, a viral pneumonia known as coronavirus disease 2019 (COVID-19), was originated from China and spread very rapidly in the world. Therefore, COVID-19 became a global concern and health problem. Methods: We presented four patients in this study. They were selected from patients who presented with pneumonia symptoms and were suspicious for COVID-19 and referred to the intended centers for COVID-19 diagnosis and management of Shiraz University of Medical Sciences in the south of Iran. Two nasopharyngeal and oropharyngeal throat swab samples were collected from each patient and tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection by real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR), and also samples were sent for influenza viruses and all the respiratory panel. Results: In the present report, four patients were diagnosed in the starting days of COVID-19 disease in our center in south of Iran with co-infection of SARS-CoV-2 and influenza virus. Conclusions: This co-infection of COVID-19 and influenza highlights the importance of considering SARS-CoV-2 PCR assay regardless of other positive findings for other pathogens in the primary test during the epidemic.

Polymyositis is a rare condition with an unknown etiology occurring more frequently in adult women. There is a lack of evidence on the coexistence of PM and CMV infection in a patient with Hashimoto Thyroiditis hypothyroidism. However, the increasing incidence of CMV infection and autoimmune diseases overlapping points out a relationship, while the association direction remains unclear. Case outline: A 32-year-old woman recently treated for HT hypothyroidism was admitted to the hospital two weeks after being treated for common flu by the family doctor, complaining about a worsening condition with muscle pain, weakness, frequent falls, and fatigue. The first tests showed a normalized thyroid function, with elevated values of troponin and serum creatinine kinase (KC). The immunological tests revealed the presence of a high titer of CMV IgG antibodies and raised levels of CMV DNA. Pelvis MRI images demonstrated markedly elevated signals on the STIR sequences in the pelvis, thighs, and calves, indicating active and severe multifocal myositis. The diagnosis of PM was confirmed with the muscle biopsy on day 7 of hospitalization. The patient showed significant improvements within two weeks after the medical therapy and physiotherapy.

(1) Background: Respiratory infections are a major public health problem worldwide, with potentially serious consequences. Indeed, these infections remain one of the main causes of morbidity and mortality in children under 5 years old in developing countries. Etiological information on respiratory infections is crucial for prevention and case management strategies. This systematic review aims to describe the etiology of respiratory infections reported in studies carried out in sub-Saharan African countries; (2) Methods: Using PubMed, HINARI and Google scholar search engines, a systematic search was carried out to identify published articles on the etiology of viral and/or bacterial respiratory infections in sub-Saharan Africa in patients of all ages. We have only considered data from sub-Saharan Africa. Papers published from 2010 to 2021, in English or French have been included in this review; (3) Results: After reviewing 115 articles reporting studies carried out in the African continent, only 32 articles were selected of which, studies were conducted in 15 sub-Saharan African countries, including 6/32 (18.75%) in Cameroon. Twenty (62.5%) were cross-sectional studies, and twenty-four (75%) were hospital-based investigations. In these studies, RT-PCR and culture methods were respectively used for viruses and bacteria investigations. Respiratory syncytial virus was the most frequently identified, with prevalence ranging from 0.6% to 59%, followed by rhinovirus (9.3% -73%), influenza virus (flu) A/B (0.9%-69.1%), and human adenovirus (0.9% - 30.8%). Streptococcus pneumoniae (14.2% - 96%), followed by Haemophilus influenzae type b (2.5% - 54%), and Klebsiella pneumoniae (1.4% - 49.9%) were the most frequently detected bacteria; (4) Conclusions: This review has reported that many pathogens, mainly viruses, are associated with acute respiratory infections in sub-Saharan Africa in both children and adults. Unfortunately, the limited geographical distribution of data across sub-Saharan Africa does not allow most of countries to develop an effective strategy for the prevention and treatment of respiratory infections.

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique at-tributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two preg-nancies, which occurred 4 years apart, without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no evidence of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus.

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissoci-ated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9-days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular via-bility over time. Overall, this human-centered model offers a promising resource to study the cel-lular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics.

Severe Acute Respiratory Syndrome Coronavirus - 2 (SARS-CoV-2), later renamed Coronavirus Disease 2019 (COVID-19) was first identified in Wuhan, China, in early December 2019. Initially, the China office of the World Health Organization was informed of numerous cases of pneumonia of unidentified etiology in Wuhan, Hubei Province on December 31, 2019. This would subsequently result in a global pandemic with over 76 million confirmed cases of COVID-19 and 6.9 million deaths reported to the WHO. We have analyzed most of the data published since the beginning of the pandemic to compile this comprehensive review of SARS-CoV-2. We look at the core ideas, such as the etiology, epidemiology, pathogenesis, clinical symptoms, diagnostics, histopathologic findings, consequences, therapies, and vaccines. We have also included the long-term effects and myths associated with some therapeutics of COVID-19. This study comprehensively assesses of the SARS-CoV-2 virology, vaccines, medicines, and significant variants identified during the pandemic. Our review article is intended to provide medical practitioners with a better understanding of the fundamental sciences, clinical treatment, and prevention of COVID-19. As of June 2023, this paper contains the most recent data made accessible.

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.

Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of infections. The risk of presenting herpes zoster (HZ) is 1.5-2 times higher than in immunocompetent individuals and disseminated presentation is more frequent. Our aim was to analyze the prevalence and general features of HZ in RA patients. Methods: Prospective study of 392 RA patients included in the vaccination program of our hospital between 2011 and 2016, and followed-up until December 2020. Diagnosis of HZ was made according to clinical manifestations: skin rash, blisters, paresthesia and local pain in one or more dermatomes. Results: We studied 392(309women/83men), mean age 59±13years. Every patient was followed-up during a mean period of 137±110 months (range: 42months- 42years). HZ infection was observed in 30 of 392 (25women/5men) patients; age (mean±SD) 64.7±11.8years. Prevalence was 7.65% in this period and incidence rate was 13.22/1000patients/year. Three patients had facial involvement, one with optic involvement and one patient presented a disseminated HZ. Seven patients presented postherpetic neuralgia treated with gabapentinoids. The main features of RA of these 30 patients were: positive RF(n=17; 56.6%), positive anti-CCP(13; 43.3%) and erosive disease(10; 33.3%). At HZ infection they were in treatment with glucocorticoids (19; 63.3%), conventional DMARDs (15; 50%), biological DMARDs (15; 50%), tofacitinib (2; 6.6%) and upadacitinib (1; 3.3%). Conclusions: HZ is a relative frequent viral complication of RA patients. In our series, one patient presented a disseminated HZ and nearly 25% of patients had post-herpetic neuralgia. Include HZ vaccine in our vaccination program in RA patients may be beneficial.

Exacerbated inflammatory responses are a hallmark of severe coronavirus disease 2019 (COVID-19). Zileuton (Zi) is a selective inhibitor of 5-lipoxygenase, an enzyme involved in the production of several inflammatory/pro-resolving lipid mediators. Herein, we investigated the effect of Zi treatment in a severe acute respiratory syndrome (SARS) model. Mouse hepatitis virus (MHV)3-infected mice treated with Zi significantly improved the clinical score, weight loss, cardiopulmonary function, and survival rates compared with infected untreated animals. The protection observed in Zi-treated mice was associated with a lower inflammatory score, reduced dendritic cell-producing tumor necrosis factor (TNF), and increased neutrophil-producing interleukin (IL)-10 in the lungs 3 days after infection (dpi). At 5 dpi, the lungs of treated mice showed an increase in Th2-, Treg CD4+-, and Treg CD8+-producing IL-10 and reduced Th1 infiltrating cells. Furthermore, similar results were found upon Zi treatment after SARS-CoV2 infection in transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter (K18-hACE2), significantly improving the clinical score, weight loss, and lung inflammatory score compared with untreated animals. Our data suggest that Zi protects against developing severe lung disease during SARS induced by betacoronavirus without affecting the host’s capacity to deal with infection.

Aim: Aim of our study to evaluate various factors responsible for surgical site infection after gastrointestinal and hepatobiliary surgeries. Material and Methods: Patient who underwent gastrointestinal and hepatobiliary surgery in our department were evaluated retrospectively. Various factors associated with surgical site infection were evaluated using univariate and multivariate analysis. Surgical site infection was defined as any culture positive discharge from the wound within 30 days of surgery.Statistical analysis was done using SPSS version 23. Results: We evaluated total 331 patients operated between April 2018 to March 2020. 14 patients were lost to follow up after discharge and before completing post operative day 30. 18 patients expired before 30 days without developing SSI and were excluded from the study as per exclusion criteria. 299 patient included in the study. Total 20 patients developed surgical site infection. It showed SSI rate in our study population was 6.68%. On univariate analysis prolonged hospital stay, more blood product used, higher cdc grade of surgery, higher ASA grade, more operative time, open surgeries,colorectal and HPB surgeries were associated with surgical site infections. On multivariate analysis only prolonged hospital stay independently predicted Surgical Site Infectins. (p=0.014,0dds ratio 1.223, 95% confidence interal 1.042-1.435). Conclusion: Prolonged hospital stay independently predicts surgical site infections after gastrointestinal and hepatobiliary surgery.

Lytic bacteriophages have the efficacy to act and eradicate pathogenic bacteria as an attractive tool in the near future. Bacteriophages specifically kill multidrug-resistant bacteria even which have the capacity to form biofilms. The present review mainly focused on the efficacy of bacteriophages and cocktails as therapeutic agents against predominate MDR-bacteria and their biofilms which are isolated from septic wound infections. The body of evidence includes data from studies investigating bacteriophages from sewage samples as novel antibacterial and antibiofilm agents against pathogenic bacteria. The goal of this review is to present an overview on predominant bacteria from septic wound infection, the biofilm-forming capacity of bacteria, lytic effect of bacteriophages and phage cocktails with an emphasis on the application of bacteriophages against septic wound causing bacteria.

Purpose: Surgical site infection (SSI) is a significant complication of non-reconstructive and reconstructive breast. This study aimed to assess SSI after breast surgery over 5 years in a single center in Poland. The microorganisms responsible for SSI and their antibiotic susceptibility were determined. Materials/methods: Data of 2129 patients acquired over 5 years postoperatively by the [center] were analyzed. Results: SSI was diagnosed in 132 patients (6.2%) and was an early infection in most cases (65.2%). The incidence of SSI was highest in patients who underwent subcutaneous amputation with simultaneous reconstruction using an artificial prosthesis (14.6%) and breast reconstruction via the TRAM flap method (14.3%). Gram-positive bacteria were responsible for SSI in most cases (72.1%), and these were mainly Staphylococcus strains (53.6%). These strains were 100% susceptible to all beta-lactam antibiotics (except penicillin), but were less susceptible to macrolides and lincosamides. Conclusions: SSI is a serious problem, and attention should be focused on its prevention. Reconstruction using an artificial prosthesis or via the TRAM flap method is connected to increased SSI incidence. Further studies are required to prevent SSI following breast surgery.

Tuberculosis (TB) associated with diabetes (DM) is a growing problem, particularly in low and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment with isoniazid (INH) or rifampicin (RIF) in people with DM. Participants were assigned six months of INH 300mg/day plus pyridoxine 75mg or three months of RIF 600mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TB preventive treatment is not safe enough to be considered a universal indication to patients with DM and LTBI. These results underline the need to search for alternative TB prevention in DM patients with better safety profiles.

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

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.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

.Various synthetic nematicides are currently used effectively in the control of plant parasitic nematodes. However, these nematicides have adverse effects on humans and the environment. Neem oil is eco-friendly alternatives to synthetic nematicides. The effectiveness of repeated neem oil application in suppressing the root-knot nematodes infestation in figs seedlings was therefore examined in this study, both in its natural form (10 ml/L) and in its nano-emulsion form (5 and 7 ml/L). The recorded reduction parameters of M. incognita were J2/250g soil, galls and egg masses / 5g roots of infected fig seedlings were measured at that time, and the effects of these natural additives were compared with the Fosthiazate (Krenkel 75%EC). The impact of such soil amendments on some typical plant parameters, the total microbial count of soil, and the overall enzymatic activity of the fig rhizosphere were also included. Obtained results revealed that the soil population density of root knot nematode suppressed by 80.3% , reduction of nematode egg masses (60.4%) due to the application of nano-emulsion of neem oil (at 7ml/L). Present work recommend the use of nano-emulsion of neem oil as one of the effective and eco-friendly means to reduce the root- knot nematode on fig .

This review revisits clinical use of antibiotics for most common acute oro-dental conditions; we aim to provide evidence governing antibiotics use when access to oral healthcare is not available, as during the ongoing outbreak of the severe acute respiratory syndrome coronavirus 2. In this rapid review, articles were retrieved after conducting a search on PubMed and Google Scholar. Relevant publications were selected and analyzed. Most recent systematic reviews with/without meta-analyses and societal guidelines were selected. Data were extracted, grouped, and synthesized according to the respective subtopic analysis. There were evidence supporting the use of antibiotics in common oro-dental conditions as temporary measure when immediate care is not accessible, such as in case of localized oral swellings as well as to prevent post-extraction complications. No sufficient evidence could be found in support of antibiotic use for pain resulting from pulpal origin. Consequently, antibiotic use may be justified to defer treatment temporarily or reduce risk of complications in case of localized infection and tooth extraction, when no access to immediate dental care is possible.

Dental services are significantly impacted by the COVID-19 pandemic. Almost all dental procedures carry a high infection risk for providers and patients due to spread of aerosols. As a consequence, national public health agencies, and dental professional associations have issued guidelines for enhanced infection control, personal protection equipment and limiting care to urgent or emergency services. However, there is no dental service concept for disaster preparedness or response that might be applied. Similarly, pathways to care provision in a post-pandemic future are missing. We propose Safe Aerosol-free, Emergent Dentistry (SAFE Dentistry) as one approach to dental services during and emerging from pandemics. The concept’s starting point is the identification of the most common patient needs. The next step is to replace common treatments relating to the most common needs with alternative interventions with less infection risk because they do not generate aerosols. SAFE Dentistry is innovative, safe, and responds to the requirements of a pandemic and post-pandemic emergence where the risk of disease transmission remains high. SAFE Dentistry thereby ensures continuity of dental services while protecting providers and patients from infectious pathogens. Moreover, SAFE Dentistry allows dental service providers to remain operational and generate income even under pandemic conditions. Implementation and policy options for SAFE Dentistry include universal availability without co-payments by patients and a uniform bundled payment scheme for providers to simplify budgeting, reimbursement and to provide easier administration during a pandemic. Adaptations and adjustments of the concept are possible and encouraged, as long as the principle of avoiding aerosol-generation is maintained.

Worldwide, among older adults, infection is the leading mortality cause; chronic nutritional deficits confer significant mortality risk and increase healthcare costs. The association of the Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition with infection-related mortality, especially with renal dysfunction in older patients, remains unevaluated. In older patients hospitalized with infection, stratified by renal function, we investigated the association of malnutrition severity with mortality. This single-center, retrospective cohort study of 1220 participants (age ≥65 years) admitted to Aichi Medical University from 2019 to 2020 used a multivariate Cox proportional hazards model to determine the association of GLIM-defined nutritional status (no, moderate, or severe malnutrition) with all-cause mortality. Compared to no malnutrition, moderate and severe malnutrition conferred significantly higher mortality (adjusted hazard ratio [confidence interval ]: 1.00 [reference], 1.76 [1.28-2.42], and 2.44 [1.78-3.33], respectively), with the highest all-cause mortality in malnutrition with a low estimated glomerular filtration rate (eGFR &lt;30 mL/min/1.73m2; 7.35 [4.57-11.8]) compared to no malnutrition and normal eGFR (≥60 mL/min/1.73m2). GLIM-defined malnutrition confers higher all-cause mortality risk in older adults with infection, especially those with renal dysfunction. This information enables the identification of high-risk older patients with infection and targeted clinical management of those with malnutrition, renal dysfunction, and infection.

Abstract: (1) Background: No consensus has been reached on indicators and protocols for monitoring drug concentrations in organ transplant recipients for the immunosuppressant mycophenolic acid (MPA) in clinical therapy.In this study, we propose to establish a Ultra Performance Liquid Chromatography–Tandem Mass Spectrometry (UPLC-MS/MS) for quantitative determination of MPA and its metabolites ( mycophenolic acid carboxybutoxyether, MPAG and mycophenolic acid carboxyglucuronide, AcMPAG) concentrations in peripheral blood mononuclear cells (PBMCs) and to assess the clinical application of PBMCs concentration detection of MPA and its metabolites in infection prediction in Chinese kidney transplant recipients(KTRs); (2) Methods: PBMCs were isolated with Ficoll-Paque solution, and cells were counted. Acetonitrile precipitated proteins to extract the target compounds.Waters ACQUITY UPLC BEH C18 column of 1.7μm (2.1 mm*50 mm) and an ACQUITY-Xevo TQ-S UPLC-MS/MS system were used for the detection with mobile phases: water and methanol (containing 2 mmol/L NH4Ac + 0.1% formic acid); flow rate: 0.3 mL/min. After gradient elution, the samples were positively ionized by an electrospray positive ion source (ESI) and then quantitatively analyzed by a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode. The performance of the established method was evaluated through a series of validation experiments according to the requirements of the relevant guidelines. We enrolled 7 KTRs with stable conditions and 8 KTRs with infection from August to November 2022, who were treated at the West China Hospital of Sichuan University.Their peripheral blood samples were collected and detected MPA, MPAG, and AcMPAG concentrations in PBMCs using the methods mentioned above and evaluated for their clinical application in the prediction and monitoring of infections in KTRs; (3) Results: After validation of the methodology, the UPLC-MS/MS method established in this study for the determination of MPA, MPAG, and AcMPAG concentrations in PBMCs showed good linearity in the quantitative ranges of 0.0625-50 ng/ml, 0.5-50 ng/ml and 0.1-20 ng/ml, and the selectivity, specificity, matrix effect, carry-over contamination, reproducibility, precision and accuracy all satisfied the requirements.AcMPAG in PBMCs was poorly stabilized and showed significant degradation after -80°C storage for 24 h or 3 cycles of freeze-thaw.There was a large variability in MPA and MPAG concentrations in PBMCs of KTRs and it correlated poorly with plasma MPA concentrations (rs=0.206,p=0.117).Subgroup analysis showed that the correlation between MPA in plasma and PBMCs was still poor in the infected group(rs=0.201,p=0.116), but significant correlation in the stable group (rs=0.643,p=0.001). A significantly higher level of MPA in PBMCs was observed in the infected group than those in the stable group at 2h and 4h after drug dosing (p&lt;0.05).AcMPAG concentrations in PBMCs of KTRs were extremely low and virtually undetectable.ROC curve analysis (area under the curve, AUC) was performed for infection after renal transplantation with indicators of significant difference showed that the area AUC for PBMCs-MPA-C4 was 0.928 ,for PBMCs-MPA-C2 was 0.875,and for Plasma-MPA-C4 was 0.803; (4) Conclusions: In this study, a method based on UPLC-MS/MS was developed and validated for the simultaneous determination of MPA, MPAG, and AcMPAG concentrations in PBMCs.With easy operability and good stability, this method provides a reliable analytical method for the clinical implementation of the detection of MPA, MPAG, and AcMPAG concentrations in PBMCs.The concentrations of MPA and MPAG in PBMCs from KTRs were highly variable and were closely associated with the development of infections after renal transplantation.Monitoring MPA and MPAG in PBMCs may be useful indicators for mycophenolic acid therapeutic drug concentration monitoring (TDM) in KTRs.

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in patients with pneumonia (called COVID-19) in Wuhan, Hubei Province, China. SARS-CoV-2 shares high sequence similarity and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as does severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes for SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not been determined. Here, we investigate the expression pattern of ACE2 in adult human testis at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia, Leydig and Sertoli cells. Gene ontology analyses indicate that GO categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia while male gamete generation related terms are down-regulated. Cell-cell junction and immunity related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction related GO terms are decreased. These findings provide evidence that human testes are a potential target of SARS-CoV-2 infection which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Sink waste traps and drains are a reservoir for multi-drug resistant Gram-negative bacteria in the hospital environment. It has been suggested that these bacteria can migrate through hospital plumbing. Hospital waste traps were installed in a laboratory model system where sinks were connected through a common wastewater pipe. Enterobacterales populations were monitored using selective culture, MALDI-TOF identification and antibiotic resistance profiling before and after a wastewater backflow event. When transfer between sinks was suspected, isolates were compared using whole-genome sequencing. Immediately after the wastewater backflow, two KPC-producing Enterobacter cloacae were recovered from a waste trap in which Carbapenemase-producing Enterobacterales (CPE) had not been detected previously. The isolates belonged to ST501 and ST31 and were genetically indistinguishable to those colonising sinks elsewhere in the system. Following inter-sink transfer, KPC-producing E. cloacae ST501 successfully integrated into the microbiome of the recipient sink and was detected in the waste trap water at least six months after the backflow event. Seven weeks and three months after the backflow, other inter-sink transfers involving Escherichia coli ST5295 and KPC-producing E. cloacae ST501 were also observed.

ntroduction: Respiratory tract Infections are the greatest cause of death worldwide. Since its outbreak in 2019, the coronavirus pandemic (COVID-19) has been a challenge to humans in terms of treatment and prevention of this respiratory viral infection. The re-emergence of respiratory viral infections like influenza, pose a serious hazard to global public health because they occur seasonally. Creating broad-spectrum antiviral compounds for rapid action in the case of an outbreak crisis, as well as bioweapon defences, is critical. Human galectin-3 is found in high concentrations in activated T lymphocytes, epithelial and endothelial cells, and fibroblasts. ProLectin -I and ProLectin -M are both galectin antagonists. Blocking viral entry with a complex polysaccharide component "ProLectin-M" has downstream effects on viral reproduction enabling it to be used as a therapeutic tool and a safe alternative to conventional anti-viral medicines. Methods: In total, 3 cell based assays have been conducted to evaluate antiviral efficacy of ProLectin–I and ProLectin-M against SARS-CoV-2 virus, Influenza-A (H1N1), and human respiratory syncytial virus (hRSV) strain A2. ProLectin-M and ProLectin-I were evaluated for their anti-viral potency using SARS-CoV2 virus strain by viral RNA Extraction and qRT-PCR assays. The plaque assays were carried out to determine the antiviral activity of the test products (ProLectin-I and ProLectin-M) against ‘Influenza-A (H1N1)-A/PR/8/34 (TC adapted)’ and ‘Human respiratory syncytial virus (hRSV) strain A2’ in a cell based in vitro setting. As eference standard, "Oseltamivir Phosphate" and "Remdesivir" were used to determine antiviral activity of test products against H1N1 and hRSV strains respectively.Results: The IC_{50 of} ProLectin-M and ProLectin-I against SARS-CoV-2 virus was found to be 6248 ng/ml (6.2µg/ml) and 4207 ng/ml (4.2μg/ml) respectively. The CC₅₀ value was similar in both the test products i.e. >100 µg/ml. Against Influenza A (H1N1) strain, ProLectin-M exhibited 95 % reduction in the viral load at the test concentration of 21.8 µg/mL with an IC₅₀ value of 5.4 µg/mL whereas, ProLectin-I did not show any cytotoxicity till 250 µg/mL concentration. Against 'human respiratory syncytial virus (hRSV) strain A2, ProLectin-M exhibited 65 % reduction in the viral load at the test concentration of 43.75 µg/mL with an IC₅₀ value of 27.41 µg/mL whereas, ProLectin- I did not show any cytotoxicity till 250 µg/mL concentration. Conclusion: Both ProLectin-I and ProLectin-M have been reported to exhibit broad-spectrum antiviral activity in ‘in-vitro’ setting. ProLectin-M reducing influenza-A virus by 95% and hRSC strain A2 by 65%. To better understand broad spectrum antiviral activity of ProLectin-I and ProLectin-M, further pre-clinical research is warranted.

Toxocarosis remains an important neglected parasitic infection representing one of the most common zoonotic infections caused by the parasite Toxocara canis or less frequently by Toxocara cati. The epidemiology of the disease is complex due to its transmission route by accidental ingestion of embryonated Toxocara eggs or larvae from tissues from domestic or wild paratenic hosts. Even though Toxocara infects about 1,4 billion people worldwide, global epidemiological data regarding the relationship between seropositivity and toxocarosis is limited. Although the vast majority of the infected individuals remains asymptomatic or experiences a mild disease, the infection is associated with important health and socioeconomic consequences, particularly in underprivileged, tropical, and subtropical areas. Toxocarosis is a disease with multiple clinical presentations, which are classified into five distinct forms: the classical visceral larva migrans, ocular toxocarosis, common toxocarosis, covert toxocarosis, and cerebral toxocarosis or neurotoxocarosis. Anthelmintic agents as for example albendazole or mebendazole is the recommended treatment, whereas a combination with topical or systemic corticosteroids for specific forms is suggested. Prevention strategies include educational programs, behavioural and hygienic changes, enhancement of the role of veterinarians, and anthelmintic regimens to control active infections.

Urinary tract infections (UTIs) are highly prevalent in long-term care facilities, constituting the most common infection in this setting. Our research focuses on analyzing clinical characteristics and antimicrobial prescriptions for UTIs in residents across nursing homes (NH) in Spain. This cross-sectional report is part of a before/after intervention study using a multifaceted approach based on the normalization process theory to improve healthcare quality provided by nursing staff in 34 NHs in Spain. In this study we present the results of the first audit including 719 UTI cases, with an average age of 85.5 years and 74.5% being women. Cystitis and pyelonephritis presented distinct symptom patterns. Notably, 6% of asymptomatic bacteriuria cases were treated. The prevalence of dipstick usage was 83%, raising concerns about overreliance, including in the 46 asymptomatic cases, leading to potential overdiagnosis and antibiotic overtreatment. Improved diagnostic criteria and personalized strategies are crucial for UTI management in NHs, emphasizing the need for personalized guidelines on management of UTIs, to mitigate indiscriminate antibiotic use in asymptomatic cases.

Abstract: The COVID-19 pandemic significantly disrupted global healthcare systems. The impacts of SARS-CoV-2 infection on urticaria and its management are unknown. To collect information about patients with urticaria infected with SARS-CoV-2 and to investigate the impact of SARS-CoV-2 infection on urticaria severity, course, and treatment to better support recovery. This was a questionnaire-based study of patients with urticaria infected with SARS-CoV-2. Changes in urticaria severity (measured with the urticaria activity score (UAS)), course, and treatment were assessed before, during, and after SARS-CoV-2 infection. Mean (± SD) UAS scores were 5.17 ± 1.67, 4.23 ± 1.98, and 4.37 ± 1.93 before, during, and after SARS-CoV-2 infection, respectively (F = 8.839, p < 0.01). The median (IQR) wheal score was 0.464 (0.464, 0.763), 0.464 (0.138, 0.763), and 0.464 (0.138, 0.763) before, during, and after infection, respectively (Kruskal-Wallis H-test, H=12.230, p = 0.02). The median (IQR) pruritus score was 0.695 (0.395, 0.695), 0.394 (0.123, 0.695), and 0.394 (0.123, 0.695) before, during, and after infection, respectively (Kruskal-Wallis H-test, H = 21.001, p < 0.01). Within the limitations of a questionnaire study, urticaria appears to improve during SARS-CoV-2 infection, worsens slightly after recovery, and the frequency of Western medicine use increases.

Human Adenovirus (HAdV) infection occurs in 14-16% of patients in the early months after pediatric hematopoietic cell transplantation (HCT) and this correlates with a higher risk to develop HAdV disease and overall 6-month mortality. The main risk factors for HAdV infection are T-cell depletion of the graft by ex vivo CD34+ selection or in vivo use of alemtuzumab or anti-thymocyte serum, the development of grade III-IV graft versus host disease (GVHD), the type of donor (unrelated donor, cord blood, haploidentical or HLA mismatched parent) and severe lymphopenia (< 0.2 x 109/L). The prevention of HAdV disease is based on early intervention with antivirals in the asymptomatic patient when the permitted viral load threshold on blood (> 102-3 copies/ml) and/or on the stool (109 copies/g stool) is exceeded. Cidofovir, a monophosphate nucleotide analog of cytosine, is the primary drug for preemptive therapy, used at 5 mg/kg/week for 2 weeks followed by 3-5 mg/kg every 2 weeks. The alternative schedule is 1 mg/kg every other day (three times/week). Enhancing virus-specific T-cell immunity in the first months post-HCT by donor-derived or third-party-derived virus-specific T cells represents an innovative and promising way of intervention applicable both in prevention and therapeutic setting.

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate E. faecalis ability to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, for example when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis.

Treating infections caused by Pseudomonas aeruginosa is increasingly difficult due to high antimicrobial resistance, materialized through the presence of multiple resistance strains, as well as due to rapid development of resistance throughout treatment. The present survey was conducted to investigate the antibiotic susceptibility profile of Pseudomonas aeruginosa pathogens, in two University Veterinary hospitals from different geographical regions of Romania (i.e., south-west - Timisoara county and north-east – Iasi county) involved in canine superficial infections. A total of 142 swab specimens were collected from dogs with superficial infections (superficial skin infections, otitis externa, perianal abscess), with the aim of assessing the presence of Pseudomonas aeruginosa, based on phenotypic and molecular characterization. Fifty-eight samples (40.84%; 58/142) were positive for Pseudomonas aeruginosa (according to their confirmed morphological and molecular features). Susceptibility to usual antibiotics used in the treatment of canine skin conditions was tested for all Pseudomonas strains that were isolated from canine superficial infections, using the Kirby Bauer disc diffusion method. Drug resistance was observed in the case of all tested antibiotics. The susceptibility rate of P. aeruginosa strains that were tested in this study was in the following order: ampicillin sulbactam (55.17%; 32/58), followed by ceftazidime (53.44%; 31/58), aztreonam (51.72%; 30/58), amikacin (44.82%; 26/58), azithromycin (41.37%; 24/58), gentamycin (37.93%; 22/58), cefepime (36.20%; 21/58) meropenem (25.86%; 13/58), piperacillin-tazobactam (25.86%; 13/58) imipenem (22.41%; 13/158), ciprofloxacin (17.24%; 10/58) tobramycin (8.62; 5/58), and polymyxin B (1.72; 1/58) respectively. The results highlight the importance of antibiotic susceptibility testing in Pseudomonas aeruginosa isolates from dogs with superficial infections, in order to use an adequate treatment plan for the management of the skin condition, and other pathology (otitis externa and perianal abscesses).

CX3CL1, also named fractalkine or neurotactin, the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in microglia of central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the roles of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and the associated diseases.

Host immunological pathways have been proposed including TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ immune reactions. Besides TH2 and TH9 immune responses which are against multicellular parasites, host immunological pathways against viruses, intracellular micro-organisms (bacteria, protozoa, and fungi), and extracellular micro-organisms can use programmed cell death pathways to trigger immune reactions or to execute effective strategies to eliminate these pathogens. These programmed cell deaths include apoptosis, autophagic death, pyroptosis, ferroptosis, necroptosis, and NETosis. Apoptosis is related to host anti-virus eradicable THαβ immunity. Autophagic death is related to host anti-virus tolerable TH3 immunity. Pyroptosis is related to host anti-intracellular micro-organism eradicable TH1 immunity. Ferroptosis is related to host anti-intracellular micro-organism tolerable TH1-like immunity. Necroptosis is related to host anti-extracellular micro-organism eradicable TH22 immunity. NETosis is related to host anti-extracellular micro-organism tolerable TH17 immunity.

Background: Sepsis still represents a major public health issue worldwide, and immune system plays a main role during infections and therefore its activity is mandatory to resolve this clinical condition In this report we aimed to retrospectively verify in real life setting the possible usefulness of Pentameric IgM plus antibiotic in recovering patients with sepsis after major abdominal surgery Materials/methods: We reviewed, from January 2013 until December 2018, all adult patients admitted in ICU for Sepsis or Septic shock (2) after major abdominal surgery. Among these patients, were identified those that according to legal indication and licence in Italy, were treated with Pentameric IgM plus antibiotic (Group A) or with antibiotic alone (Group B). We analysed the following parameters were evaluated: Blood gas analysis, Lactate, CRP, Procalcitonin, Endotoxin activity, Liver and Renal Function, Coagulation, Blood Cell count at different time points (Every 48 hrs for at least 7 days. Differences between groups have been analysed by Fisher’s exact test or Chi square test for categorical variables. Mann–Whitney U test or Kruskal–Wallis test have instead been performed to compare continuous variables. Univariate and Multivariate analysis were also performed Results: Over a period of 30 months 24 patients were enrolled in Group A and 20 patients in Group B. In those subjects no statistical differences have been found in terms of bacterial or fungal infection isolates, when detected in a blood culture test, or in inflammatory index, SOFA score, lactate levels and mortality rate. A 48hrs response was statistically more frequent in Group B than in Group A, while no differences were found in the other clinical and laboratory evaluation. Conclusions: Based on our results, the use of pentameric IgM do not seem to give any clinical advantage in sepsis after to major abdominal surgery.

A sixty-six-year-old woman with a strong family history of breast cancer noted gradual onset of axillary lymph node enlargement in 2019. Axillary lymph node biopsies disclosed Lymph node involvement by Chronic Lymphocytic Leukemia (CLL/SLL). Immunophenotype analysis of nodal tissue and of bloodstream leukemic cells in immunohistochemistry and flow cytometry and next generation molecular diagnostics confirmed CLL/SLL. Replicate absolute peripheral blood lymphocyte counts in excess of 5.0 x 10e3/microliter confirmed the numerical threshold for diagnosis of Chronic Lymphocytic Leukemia in the bloodstream. FISH studies disclosed an immunoglobulin “mutation negative” CLL/SLL genotype without a light chain restriction pattern. No translocations or germline mutations were present. Borrelia spirochetes in the bloodstream were detected with simultaneous high spirochetemia of both borrelia miyamotoi and borrelia burgdorferi. FISH hybridization of leukemic lymphocytes disclosed extensive borrelia invasion of the cytoplasm and of the nucleus compartments of CLL/SLL tumor cells. Retrospective studies of the patient’s archival stored blood smears obtained three years prior in 2016 at age 63 disclosed no evidence of CLL/SLL but confirmed asymptomatic bloodstream borrelia miyamotoi and borrelia burgdorferi borrelia infection. Lyme serology had been reported as negative in 2016. Additionally, retrospective FISH DNA hybridizations focused on preleukemic bloodstream Lymphocytes disclosed rare borrelia spirochetal adherence to benign blood lymphocytes in the year 2016 in the preleukemic blood smears. This case report is the very first to describe precursor chronic asymptomatic Lyme borreliosis and Miyamotoi borrelia bloodstream infections three years prior to the diagnosis of Rai Stage 1 Chronic Lymphocytic leukemia.

The outbreak of coronavirus disease-19 (COVID-19) has infected more than 11 million people and has claimed more than 530.000 deaths world-wide. In July 2020, still, there is no specific treatment for disease caused by the novel coronavirus. In the search to curb the global pandemic COVID-19, some eastern and developing countries have approved various treatment with controversial efficacy, among that the use of the antimalarial Hydroxychloroquine (HCQ), so far with inconclusive clinical evidence of effectiveness. On the other hand, computer-based screening suggest that HCQs analog are promising molecules, to impair viral replication in vitro[1]. Therefore, what is emerging from this complex background, is the need to understand molecular mechanism beyond drugs that can be helpful against viral infection for this and future pandemic. The intent of this Brief Report is to highlight: i) the involvement of the Mitogen Activated Protein Kinase (MAPK) cascade in viral infection and ii) the urgent need to have molecular data on the effectiveness of the combination of MAPK inhibitors together with HCQ and HCQs analogs in curbing viral infection. We are convinced that a better understanding of the patterns of elicited molecular mechanisms will be critical for new molecular approaches to this severe disease

Italy suffered heavily with the new pandemic crisis caused by the novel coronavirus SARS-CoV-2. Given the low number of tests performed on the early stages of the outbreak, Italy lost track of most of infections. We use a modified SEIR model to reconstruct the most realistic infection curve using the hospitalization curve of the registered data. Using this method we estimated that, by the end of the first infection wave, about 3-4% of the population will have been infected by the virus. Following the same process, the number of deaths is projected to be between 100000 to 115000. We also find a significant correlation between the number of tests performed, the fraction of undocumented infections and the rate of change dI/dt of the real infection curve. We conclude that herd immunity is not enough to contain further spread of the disease inside the country.

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.

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

Respiratory viral infections (RVI) are common reasons for healthcare consultations. The inpatient management of RVI consumes significant resources. From 2009-2014, we assessed the costs of RVI management in 4776 hospitalized chil-dren aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by de-tailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (“non-ICU”) versus management requiring ICU-care (“ICU”) added up to 2,767.14€ (non-ICU) vs. 29,941.71€ (ICU) for Influenza, 2,713.14€ (non-ICU) vs. 16,951.06€ (ICU) for RSV infections, and 2,767.33€ (non-ICU) vs. 14,394.02€ (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all 8 RVI studied: Influenza, RSV, hRV, ade-novirus (hAdV), metapneumovirus (hMPV), parainfluenzavirus (hPIV), bocavirus (hBoV) and seasonal coronavirus (hCoV) infections. ICU-costs for Influenza however, ex-ceeded all other RVI. At the time of the study, Influenza was the only RVI with antivi-ral treatment options available for children, but only 9.8% of Influenza patients (non-ICU) and 1.5% of ICU-patients with Influenza received antivirals; only 2.9% were vac-cinated. Future studies should investigate the economic impact of treatment and pre-vention of Influenza-, COVID-19-, and RSV post vaccine introduction.

Lenalidomide-based regimens are effective treatment options for patients with relapsed/refractory multiple myeloma (RRMM). However, they are associated with an increased risk of infectious complications. This study examines the clinical factors influencing the occurrence of infection in MM patients treated with lenalidomide and dexamethasone (Rd). A retrospective analysis of all patients who received the Rd regimen between 2017-2021 at our institution was performed. The study group consisted of 174 patients and the median age was 65 years. Most patients (n=110, 63.2%) received the Rd treatment in second-line treatment. The majority of patients (64.3%) received bortezomib-based regimens in the first line of treatment. The median progression-free survival was 12.6 (95% CI: 9.5 – 16.2) months, and the median overall survival was 22.3 (95% CI: 15.9 – 28.6) months. The overall response rate was 64.1%, 12.7% of patients achieved complete response and 20.4% had a very good partial response. In multivariate logistic regression analysis, hypoalbuminemia (OR 4.2, 95%CI:1.6-11.2, p= 0.0039), autologous hematopoietic stem cell transplantation (AHSCT) before Rd (OR 2.6, 95% CI:1.0- 6.7, p= 0.048) and anemia grade ≥3 (OR 5.0, 95%CI: 1.8-14.0, p= 0.002) were independent factors related to the occurrence of infections. In conclusion, in this large cohort of RRMM patients, AHSCT before Rd regimen therapy, hypoalbuminemia and anemia during treatment were identified as three independent factors influencing the frequency of infections during Rd therapy. Patients with established risk factors may benefit from optimal supportive therapy.

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.

Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. Conclusions: From a regulatory perspective, D-mannose maintains the current medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose.