Zika virus non-coding RNAs antagonize antiviral responses by PKR-mediated translational arrest.

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor.

Bioinformatics Analysis Reveals E6 and E7 of HPV 16 Regulate Metabolic Reprogramming in Cervical Cancer, Head and Neck Cancer, and Colorectal Cancer through the PHD2-VHL-CUL2-ELOC-HIF-1α Axis.

Human papillomavirus 16 (HPV 16) infection is associated with several types of cancer, such as head and neck, cervical, anal, and penile cancer. Its oncogenic potential is due to the ability of the E6 and E7 oncoproteins to promote alterations associated with cell transformation. HPV 16 E6 and E7 oncoproteins increase metabolic reprogramming, one of the hallmarks of cancer, by increasing the stability of hypoxia-induced factor 1 α (HIF-1α) and consequently increasing the expression levels of their target genes. In this report, by bioinformatic analysis, we show the possible effect of HPV 16 oncoproteins E6 and E7 on metabolic reprogramming in cancer through the E6-E7-PHD2-VHL-CUL2-ELOC-HIF-1α axis. We proposed that E6 and E7 interact with VHL, CUL2, and ELOC in forming the E3 ubiquitin ligase complex that ubiquitinates HIF-1α for degradation via the proteasome. Based on the information found in the databases, it is proposed that E6 interacts with VHL by blocking its interaction with HIF-1α. On the other hand, E7 interacts with CUL2 and ELOC, preventing their binding to VHL and RBX1, respectively. Consequently, HIF-1α is stabilized and binds with HIF-1ß to form the active HIF1 complex that binds to hypoxia response elements (HREs), allowing the expression of genes related to energy metabolism. In addition, we suggest an effect of E6 and E7 at the level of PHD2, VHL, CUL2, and ELOC gene expression. Here, we propose some miRNAs targeting PHD2, VHL, CUL2, and ELOC mRNAs. The effect of E6 and E7 may be the non-hydroxylation and non-ubiquitination of HIF-1α, which may regulate metabolic processes involved in metabolic reprogramming in cancer upon stabilization, non-degradation, and translocation to the nucleus.

Prospective cohort study of incidence and risk factors for catheter-associated urinary tract infections in 145 intensive care units of 9 Latin American countries: INICC findings.

PURPOSE: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in Latin American Countries. METHODS: From 01/01/2014 to 02/10/2022, we conducted a prospective cohort study in 145 ICUs of 67 hospitals in 35 cities in nine Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Panama, and Peru. To estimate CAUTI incidence, we used the number of UC-days as the denominator, and the number of CAUTIs as numerator. To estimate CAUTI RFs, we analyzed the following 10 variables using multiple logistic regression: gender, age, length of stay (LOS) before CAUTI acquisition, UC-days before CAUTI acquisition, UC-device utilization (DU) ratio, UC-type, hospitalizationtype, ICU type, facility ownership, and time period. RESULTS: 31,631 patients, hospitalized for 214,669 patient-days, acquired 305 CAUTIs. The pooled CAUTI rate per 1000 UC-days was 2.58, for those using suprapubic catheters, it was 2.99, and for those with indwelling catheters, it was 2.21. The following variables were independently associated with CAUTI: age, rising risk 1% yearly (aOR = 1.01; 95% CI 1.01-1.02; p < 0.0001 female gender (aOR = 1.28; 95% CI 1.01-1.61; p = 0.04), LOS before CAUTI acquisition, rising risk 7% daily (aOR = 1.07; 95% CI 1.06-1.08; p < 0.0001, UC/DU ratio (aOR = 1.14; 95% CI 1.08-1.21; p < 0.0001, public facilities (aOR = 2.89; 95% CI 1.75-4.49; p < 0.0001. The periods 2014-2016 and 2017-2019 had significantly higher risks than the period 2020-2022. Suprapubic catheters showed similar risks as indwelling catheters. CONCLUSION: The following CAUTI RFs are unlikely to change: age, gender, hospitalization type, and facility ownership. Based on these findings, it is suggested to focus on reducing LOS, UC/DU ratio, and implementing evidence-based CAUTI prevention recommendations.

Laboratory Findings in Children with Excess Body Weight in Romania.

Background and Objectives: Childhood obesity has been increasing at a worrisome pace and emerging as a non-infectious pandemic in the pediatric population in recent years. Raising awareness on this problem is of utmost importance, in order to take action to control body weight from an early age. Materials and Methods: We performed a retrospective study among overweight or obese children evaluated on an outpatient basis in the Department of Pediatric Endocrinology of a tertiary care hospital in Bucharest Romania in 2021 in order to identify laboratory changes occurring according to age and sex. Results: A total of 268 children were included in the analysis, with a median age of 10.9 years (IQR: 8.3, 13.3 years); 61.8% were obese and 38.2% overweight. We identified a subclinical pro-inflammatory status characterized by increased neutrophil count (12.7%) and increased C-reactive protein (16.4%). Biochemically, we identified the highest increases for uric acid (35.4%). More than half of the children included in the study had dyslipidemia-specific changes: high low-density lipoprotein cholesterol (LDL) (50.0%), low high-density lipoprotein cholesterol (HDL) (58.9%) and increased triglyceride levels (12.7%), especially children with a body mass-index (BMI) percentile above 95%. Increased thyroid stimulating hormone (TSH) was identified in 20.3% and low thyroxine (T4) level in 13.4%, especially in females. Conclusions: Early measures to control excess body weight are needed since preventing obesity is easier than treating it. However, this is often difficult to do in our country because parents frequently do not recognize the problem until it is advanced. Furthermore, doctors are not always adequately prepared and sometimes they do not have the support of the health systems to provide children in need with the adequate care. Educational strategies and awareness of issue should be revisited in current post-pandemic context that facilitates increase of obesity prevalence in children. Increase of efficient communication could be achieved by pointing to these objective findings.

Ophthalmological Manifestations in People with HIV from Northeastern Romania.

Background and Objectives: Although ocular disorders can occasionally impact people with HIV over the course of their illness, HIV/AIDS is unmistakably a multisystem disorder. A physician can rule out a wide range of ophthalmic problems with the assistance of an ophthalmologist, from adnexal disorders to posterior segment diseases, including those affecting the optic tract and optic nerve. Materials and Methods: Based on patient medical data from the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi, we carried out a retrospective clinical investigation on patients with HIV/AIDS and ophthalmological conditions who were hospitalized in northeastern Romania. We seek to draw attention to the characteristics and ophthalmological comorbidities of HIV/AIDS patients. The studied period was between 1 January 1991 and 31 December 2022. Results: There were a total of 38 recorded cases of ophthalmological manifestations in the HIV-infected patients. The research group's average age was 37.31 years old (standard deviation 9.5693917). Males were primarily impacted, having lower total CD4+ T-lymphocyte levels based on sex and CD4+ T-lymphocyte levels overall. The HIV viral load was 999 268.13 copies/mL on average (standard deviation 1,653,722.9). Of all the patients, we found out that 17 had congenital eye diseases (44.73%) and the others (21, 55.26%) developed ophthalmological diseases. CMV Retinitis was found most frequently, in eight patients (21.05%), followed by Myopia in seven patients (18.42%). Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach and access to antiretroviral therapy. Anyone who is HIV-positive and experiences ocular symptoms at any time should be directed to seek professional ophthalmologic treatment as soon as feasible. A therapeutic holdup could result in irreversible vision loss. Long-term coordination is required to combat this disease, improving communication between the ophthalmology and infectious disease fields.

Diagnostic Performance of IgE Anti-Der p 10 to Identify Patients with Shrimp Allergy.

BACKGROUND: Patients with allergic rhinitis to house dust mites have an increased risk of shrimp allergy. Der p 10 is a candidate biomarker to predict the risk of shrimp allergy among allergic rhinitis patients. OBJECTIVES: The aim of this study was to evaluate the diagnostic performance of anti-Der p 10 IgE as a predictor of shrimp allergy. METHODS: A nested case-control study was carried out with eighty-six allergic rhinitis patients sensitized to mite (Dermatophagoides pteronyssinus) and shrimp (Litopenaeu vannamei). Cases and controls were defined by anti-Der p 10 IgE results. Oral challenge with shrimp was used as the gold standard for the evaluation of diagnostic performance. RESULTS: All shrimp oral challenge test (OCT)-positive patients were positive for IgE against Der p 10. The level of anti-Der p 10 IgE >1.2 kUA/mL had the best diagnostic performance (sensitivity 100%, specificity 65%) Conclusion: Anti-Der p 10 IgE is useful for predicting shrimp allergy diagnosis and could reduce the requirement of an OCT.

Four Swedish cases of CSF1R-related leukoencephalopathy: Visualization of clinical phenotypes.

Colony stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare, genetic disease caused by heterozygous mutations in the CSF1R gene with rapidly progressive neurodegeneration, behavioral, cognitive, motor disturbances. OBJECTIVE: To describe four cases of CSF1R-related leukoencephalopathy from three families with two different pathogenic mutations in the tyrosine kinase domain of CSF1R and to develop an integrated presentation of inter-individual diversity of clinical presentations. METHODS: This is an observational study of a case series. Patients diagnosed with CSF1R encephalopathy were evaluated with standardized functional estimation scores and subject to analysis of cerebrospinal fluid biomarkers. Brain computed tomography (CT) and magnetic resonance imaging (MRI) were evaluated. We performed a functional phosphorylation assay to confirm the dysfunction of mutated CSF1R protein. RESULTS: Two heterozygous missense mutations in the CSF1R gene were identified, c.2344C>T; p.Arg777Trp and c.2329C>T; p.Arg782Cys. A phosphorylation assay in vitro showed markedly reduced autophosphorylation in cells expressing mutations. According to ACMG criteria, both mutations were pathogenic. A radiological investigation revealed typical white matter lesions in all cases. There was inter-individual diversity in the loss of cognitive, motor-neuronal, and extrapyramidal functions. CONCLUSIONS: Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.

Validation of an instrument to assess food diversity in women of childbearing age in Medellín, Colombia.

OBJECTIVE: To validate a Food Diversity Questionnaire (CDA, for its name in Spanish) that identifies the prevalence of the risk of deficiency in the intake of eleven micronutrients. DESIGN: The CDA paper form, an online application for data entry and handling, was designed and compared with the 24-h recall (24HR) as a reference method. All data were processed in Personal Computer Software for Intake Distribution Estimation (PC-SIDE) v1 software. A descriptive analysis and comparisons between prevalence, concordance and reproducibility analyses were performed. SETTING: Medellín, Colombia. PARTICIPANTS: Women of childbearing age between 19 and 50 years (n 186) who worked for the Buen Comienzo programme in 2019. RESULTS: When comparing the adjusted 24HR technique and the CDA, there was no significant difference in population-level data at risk of deficiency in any micronutrient intake. However, based on individual-level data of the best linear unbiased predictor, the concordance analyses were weak, and although agreements were high according to the diagnostic performance tests, a good ability to detect deficiency was only observed in a few nutrients: vitamin A 100·0 %, Ca 98·7 %, Fe 92·8 %, folates 91·6 %, and pyridoxine 81·8 %. CONCLUSIONS: The CDA validated in this study is useful and faster at evaluating population-level data at risk of deficiency in the intake of Ca, Fe, Zn, thiamine, riboflavin, niacin, pyridoxine, folates, vitamin B12, vitamin C and vitamin A. Based on individual-level data, a good ability to detect deficiencies was observed in the intake of vitamin A, Ca, Fe, folates and pyridoxine.

Effects of dietary energy levels on Pectoralis major mixed muscle protein turnover and body composition in two broiler lines housed in different grow-out environments.

This study determined the Pectoralis (P) major mixed muscle protein turnover (PT) in two meat broiler lines, Line A and Line B, during the finishing grow-out feeding period (21-42 days) as affected by the dietary metabolizable energy (ME) levels and ambient temperatures. Experimental finishing diets consisted of 80, 90, 100, 110 and 120% ME of recommended nutrient guidelines for energy level. Fractional synthesis rates (FSR) or fractional degradation rates (FDR) were measured in P. major at day 36 and 42. Protein and fat mass gain were measured, and respective energy retention efficiencies as protein and fat (EREp and EREf) were determined. Metabolic heat production (HP) was also reported. Experimental feeding studies were conducted in cool season (24 hr mean: 69.91˚F and 63.98% RH) and in hot season (24 hr mean: 77.55˚F and 86.04% RH). Results showed that FSR or FDR values were not affected by dietary ME levels at day 36, whereas reduced FSR (p < .05) were observed at day 42 fed diets with reduced ME levels (≤100% ME) which could have resulted from greater maintenance energy requirement of maturing broilers at that age. Broilers fed reduced ME diets (≤100% ME) maintained protein mass (equivalent to broilers fed ≥100%-120% ME) by reduced FDR and increased feed intake. Grow-out ambient temperature did not affect FSR or FDR values across ME levels. Line B retained higher protein mass, lower fat mass and greater HP compared to Line A. This was followed by higher feed intake in Line B. Further, Line B exhibited higher EREp and lower EREf across dietary ME levels. In summary, PT homeostasis and body composition changes in broiler lines studied seemed to be regulated by the birds' intent to normalize energy intake as per physiological need by controlling feed intake.

Device associated -health care associated infections monitoring, prevention and cost assessment at intensive care unit of University Hospital in Poland (2015-2017).

BACKGROUND: Device-associated health care-associated infections (DA-HAIs) in intensive care unit (ICU) patients constitute a major therapeutic issue complicating the regular hospitalisation process and having influence on patients' condition, length of hospitalisation, mortality and therapy cost. METHODS: The study involved all patients treated > 48 h at ICU of the Medical University Teaching Hospital (Poland) from 1.01.2015 to 31.12.2017. The study showed the surveillance and prevention of DA-HAIs on International Nosocomial Infection Control Consortium (INICC) Surveillance Online System (ISOS) 3 online platform according to methodology of the INICC multidimensional approach (IMA). RESULTS: During study period 252 HAIs were found in 1353 (549F/804M) patients and 14,700 patient-days of hospitalisation. The crude infections rate and incidence density of DA-HAIs was 18.69% and 17.49 ± 2.56 /1000 patient-days. Incidence density of ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLA-BSI) and catheter-associated urinary tract infection (CA-UTI) per 1000 device-days were 12.63 ± 1.49, 1.83 ± 0.65 and 6.5 ± 1.2, respectively. VAP(137) constituted 54.4% of HAIs, whereas CA-UTI(91) 36%, CLA-BSI(24) 9.6%.The most common pathogens in VAP and CA-UTI was multidrug-resistant (MDR) Acinetobacter baumannii (57 and 31%), and methicillin-resistant Staphylococcus epidermidis (MRSE) in CLA-BSI (45%). MDR Gram negative bacteria (GNB) 159 were responsible for 63.09% of HAIs. The length of hospitalisation of patients with a single DA-HAI at ICU was 21(14-33) days, while without infections it was 6.0 (3-11) days; p = 0.0001. The mortality rates in the hospital-acquired infection group and no infection group were 26.1% vs 26.9%; p = 0.838; OR 0.9633;95% CI (0.6733-1.3782). Extra cost of therapy caused by one ICU acquired HAI was US$ 11,475/Euro 10,035. Hand hygiene standards compliance rate was 64.7%, while VAP, CLA-BSI bundles compliance ranges were 96.2-76.8 and 29-100, respectively. CONCLUSIONS: DA-HAIs was diagnosed at nearly 1/5 of patients. They were more frequent than in European Centre Disease Control report (except for CLA-BSI), more frequent than the USA CDC report, yet less frequent than in limited-resource countries (except for CA-UTI). They prolonged the hospitalisation period at ICU and generated substantial additional costs of treatment with no influence on mortality. The Acinetobacter baumannii MDR infections were the most problematic therapeutic issue. DA-HAIs preventive methods compliance rate needs improvement.

Effects of dietary amino acid levels and ambient temperature on mixed muscle protein turnover in Pectoralis major during finisher feeding period in two broiler lines.

Two broiler lines A and B were fed experimental diets from 21 to 42 days with an objective to determine Pectoralis major protein turnover (PT) as affected by the dietary amino acid (AA) levels and ambient temperature. Experimental diets (n = 9 replicate pens per diet) were formulated to 3,150 kcal/kg with five levels of digestible lysine (dLys) -80, 90, 100, 110 and 120% of recommended AA level giving g dlys/Mcal values of 2.53, 2.85, 3.17, 3.48 and 3.80 respectively. All other AA was formulated to a fixed ratio to dLys. Fractional synthesis or degradation rates (FSR or FDR) of P. major were measured on day 36 and day 42 for all dietary treatment levels for both broiler lines using stable isotope of AA (15 N-phenylalanine) as metabolic tracer. Experimental feeding studies were conducted once in hot season (24-hr mean ~ 85.3°F; 80.9% RH) and repeated in cool season (24-hr mean ~ 71.6°F; 61.7% RH) of the year. The FSR values increased (p < .05) as digestible AA in diet increased for both broiler lines in hot season until break point FSR occurring at 106.2% AA level. The average FSR values measured were higher for Line B at day 36 (20.98%/D for Line B vs. 20.69%/D for Line A) and at day 42 (16.07%/D for Line B vs. 12.47% D for Line A). FDR values observed at day 36 and day 42 were not different between lines (p > .05). Similar trends but elevated values of FSR and FDR in cool season than in hot season were recorded for both the lines. Line B showed the higher mixed muscle protein accretion (%/D) than Line A by actually increasing the FSR which was correlated by higher lean mass deposition and higher feed intake (p < .05). The overall findings indicated that PT response in P. major due to effects of digestible AA levels and ambient temperature was different and line-specific.

Attitudes Associated with Hypochondria and Abnormal Behavior Towards Illness in Health Science Students.

The objective of this study was to evaluate attitudes towards the disease and its association with the presence of hypochondria in students of the health sciences area. The research was developed in 279 students in the health science area, with the application of Short Health Anxiety Inventory (SHAI) test and the Illness Attitude Scale (IAS) test was performed, and the descriptive, comparative and association statistical analyses were carried out. All students answered the previously mention surveys. Values above Cut-off ≥27 were obtained in the SHAI test was 6.8% (n = 19), and the percentage of students with values ≥50 Cut-off in the test of IAS was 15.7% (n = 44). IAS subtests involving an increase in the SHAI value are IAS for the disease (W), hypochondria beliefs (HB), body concerns (BP), treatment experiences (TE), and effect of symptoms (ES) with regression values of S = 3.9 with a square R adjusted to 64.9%. Therefore, according to the surveys used, a considerable sample of students showed abnormal behaviors towards the disease associated with the hypochondria, so it is important to continue monitoring students to reduce these factors.

Telomere length analysis in residents of a community exposed to arsenic.

Differentiated cells telomere length is an indicator of senescence or lifespan; however, in peripheral blood leukocytes the relative shortening of the telomere has been considered as a biological marker of aging, and lengthening telomere as an associated risk to cancer. Individual's age, type of tissue, lifestyle, and environmental factors make telomere length variable. The presence of environmental carcinogens such as arsenic (As) influence as causal agents of these alterations, the main modes of action for As described are oxidative stress, reduction in DNA repair capacity, overexpression of genes, alteration of telomerase activity, and damage to telomeres. The telomeres of leukocytes resulting a finite capacity of replication due to the low or no activity of the telomerase enzyme, therefore, elongation telomere in this kind of cells is a potential biological marker associated with the development of chronic diseases and carcinogenesis.

Contributions of BrCl, Br2, BrOCl, Br2O, and HOBr to regiospecific bromination rates of anisole and bromoanisoles in aqueous solution.

When bromide-containing waters are chlorinated, conventional wisdom typically assumes HOBr is the only active brominating agent. Several additional and often-overlooked brominating agents (including BrCl, Br2, BrOCl, Br2O) can form in chlorinated waters, albeit at generally lower concentrations than HOBr. The extent to which these additional brominating agents influence bromination rates of disinfection byproduct precursors is, however, poorly understood. Herein, the influence of BrCl, Br2, BrOCl, Br2O, and HOBr toward rates of sequential bromination of anisole was quantified. Conditions affecting bromine speciation (e.g., pH, concentrations of chloride, bromide, and chlorine) were varied, and regiospecific second-order rate constants were calculated for reactions of each brominating agent with anisole, 2-bromoanisole, and 4-bromoanisole. The regioselectivity of anisole bromination changed with pH, consistent with the participation of more than one brominating agent. Under conditions representative of chlorinated drinking water, contributions to bromination rates decreased as BrCl > BrOCl > HOBr > Br2O (Br2 negligible). The second-order rate constant determined for net bromination of anisole by HOBr is up to 3000-times less than reported in previous studies (which assumed HOBr was the only active brominating agent). Accordingly, models that assume HOBr is the only kinetically relevant brominating agent in solutions of free bromine may be insufficient for reactions involving modestly nucleophilic organic compounds.

International Nosocomial Infection Control Consortium (INICC) national report on device-associated infection rates in 19 cities of Turkey, data summary for 2003-2012.

BACKGROUND: Device-associated healthcare-acquired infections (DA-HAI) pose a threat to patient safety, particularly in the intensive care unit (ICU). We report the results of the International Infection Control Consortium (INICC) study conducted in Turkey from August 2003 through October 2012. METHODS: A DA-HAI surveillance study in 63 adult, paediatric ICUs and neonatal ICUs (NICUs) from 29 hospitals, in 19 cities using the methods and definitions of the U.S. NHSN and INICC methods. RESULTS: We collected prospective data from 94,498 ICU patients for 647,316 bed days. Pooled DA-HAI rates for adult and paediatric ICUs were 11.1 central line-associated bloodstream infections (CLABSIs) per 1000 central line (CL)-days, 21.4 ventilator-associated pneumonias (VAPs) per 1000 mechanical ventilator (MV)-days and 7.5 catheter-associated urinary tract infections (CAUTIs) per 1000 urinary catheter-days. Pooled DA-HAI rates for NICUs were 30 CLABSIs per 1000 CL-days, and 15.8 VAPs per 1000 MV-days. Extra length of stay (LOS) in adult and paediatric ICUs was 19.4 for CLABSI, 8.7 for VAP and 10.1 for CAUTI. Extra LOS in NICUs was 13.1 for patients with CLABSI and 16.2 for patients with VAP. Extra crude mortality was 12% for CLABSI, 19.4% for VAP and 10.5% for CAUTI in ICUs, and 15.4% for CLABSI and 10.5% for VAP in NICUs. Pooled device use (DU) ratios for adult and paediatric ICUs were 0.54 for MV, 0.65 for CL and 0.88 for UC, and 0.12 for MV, and 0.09 for CL in NICUs. The CLABSI rate was 8.5 per 1,000 CL days in the Medical Surgical ICUs included in this study, which is higher than the INICC report rate of 4.9, and more than eight times higher than the NHSN rate of 0.9. Similarly, the VAP and CAUTI rates were higher compared with U.S. NHSN (22.3 vs. 1.1 for VAP; 7.9 vs. 1.2 for CAUTI) and with the INICC report (22.3 vs. 16.5 in VAP; 7.9 vs. 5.3 in CAUTI). CONCLUSIONS: DA-HAI rates and DU ratios in our ICUs were higher than those reported in the INICC global report and in the US NHSN report.

The Impact of Obesity on the Host-Pathogen Interaction with Influenza Viruses - Novel Insights: Narrative Review.

After exposure to a viral pathogen, the host-pathogen interaction is essential to determine whether or not infection will ensue, and what the clinical outline of the infection will be. Recent research has shown that the patient with obesity presents a set of particular pathophysiological changes that lead to higher severity of viral infections, and this is particularly true for infection with influenza viruses. Herein, we describe the main metabolic, endocrine, and immune dysregulations that occur in the presence of obesity and their impact on driving intra-host viral diversity, leading to heightened severity and virulence of influenza. We show that obesity is linked to modified responses of both the innate and adaptive immune systems during viral infections, including influenza. Due to chronic inflammation and metabolic, endocrine, and signaling pathway disruptions, individuals with obesity have a suboptimal immune response. This results in longer illness duration, increased virus shedding, higher risk of hospitalization and complications, and greater mortality rates. Additionally, they may have a blunted response to vaccination and a higher likelihood of genetic mutation selection. Understanding the intricate interplay between obesity and viral pathogenesis is crucial for developing efficacious therapeutic approaches and public health policies, particularly in light of the escalating worldwide incidence of obesity.

Miscellaneous ophthalmic conditions related to low CD4 cell count in HIV-positive patients.

Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei Balș" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy.

Ocular involvement in highly treatment-experienced patients with HIV.

Introduction: Ocular involvement in human immunodeficiency virus (HIV) infected and treatment-experienced patients is a significant concern, despite the advancements in antiretroviral therapy (ART) medication. The extended life expectancy of HIV patients has altered the spectrum of HIV-associated ocular diseases, ranging from minor issues to severe vision impairment or blindness. Therefore, understanding these complications becomes crucial in providing comprehensive medical care and quality of life improvement. HIV patients on multiple ARTs can experience various ocular disorders due to the complexity of their treatment regimens, drug toxicities, immune reconstitution, and opportunistic infections. Most worthy to consider are: cytomegalovirus (CMV) retinitis, immune recovery uveitis (IRU), keratoconjunctivitis sicca (dry eye syndrome), and HIV-associated neuroretinal disorders. Materials and methods: A retrospective clinical investigation was conducted on HIV/AIDS-infected patients from January 1, 2013, to December 31, 2023. The study included 62 patients over 18 years, who tested HIV-positive via enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot (WB), with assessments of HIV plasma viral load (VL) and CD4+ T cell counts (CD4). Data collected included demographics, pathological histories, clinical characteristics, blood tests, assessments for opportunistic infections, patient staging, antiretroviral therapy initiation, and disease prognosis. Results: The study found that of most patients, 37 were aged 30-39 (59.7%), with 59.7% males and 40.3% females. Most had been living with HIV for 10-19 years (35.5%). Initial CD4 counts were < 200 cells/mm3 in 46.8% of patients, which improved to 19.3% when the study was done. CMV retinitis prevalence decreased from 46.8% initially to 35.5% despite ART. Other conditions included ocular toxoplasmosis (3.22%), tuberculosis-related uveitis (1,6%), keratoconjunctivitis sicca (19.3%), and HIV retinopathy (29%). Notably, 62.1% of CMV retinitis patients experienced significant visual acuity reduction. Oral valganciclovir was beneficial for patients with CMV disease affecting multiple sites and effective for both induction and maintenance therapy of CMV retinitis. Conclusions: Managing ocular complications in HIV-experienced patients requires a multidisciplinary approach with regular ophthalmologic evaluations, prompt treatment of infections, and continuous monitoring of ART effectiveness. Early detection and intervention are crucial for preserving vision and improving outcomes. The study highlighted the importance of constant monitoring even after viral suppression. Abbreviations: HIV = Human immunodeficiency virus, ART = antiretroviral therapy, CMV = cytomegalovirus, IRU = immune recovery uveitis, ELISA = enzyme-linked immunosorbent assay, WB = Western Blot, VL = viral load, CD4 = CD4+ T cells.

Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza.

Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations.

Hospitalizations for Acute Otitis and Sinusitis in Patients Living with HIV: A Retrospective Analysis of a Tertiary Center in Romania.

Background/Objectives: Acute or chronic ear, nose and throat (ENT) conditions in people living with HIV can lead to hospitalization and affect their quality of life. The aim of our study was to determine the frequency and characteristics of hospitalizations for acute sinusitis (AS) and acute otitis (AO) in people living with HIV. Methods: We performed a retrospective analysis over the course of six years (from January 2018 to December 2023), assessing all hospitalizations for AS and/or AO occurring in patients living with HIV, at the largest infectious diseases hospital in Romania. Results: We identified a total of 179 cases, among which 149 cases (83.2%) were attributed to AS and 41 cases (22.9%) were due to AO. Among cases of AS, maxillary sinuses were most frequently involved (n = 140/149, 94.0%), and among cases of AO, acute congestive otitis media (n = 14, 34.1%) and acute purulent otitis media (n = 13, 31.7%) were the most common forms. The underlying HIV infection was classified as stage C3 in 57.5% of cases. In 19.6% of cases, it was possible to identify either the trigger or the etiological agent, and the most frequent bacterial pathogens were Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. Conclusions: In conclusion, this study highlights that hospitalizations due to acute sinus and ear involvement are not isolated events in people living with HIV. A prospective follow-up is needed to gain a deeper and more dynamic understanding of how ENT health is affected in people with HIV infection. Furthermore, promoting prevention through vaccination may reduce to a certain extent the burden of ENT infections in this population.