Immunogenetic Profile Associated with Patients Living with HIV-1 and Epstein-Barr Virus (EBV) in the Brazilian Amazon Region.

Viral coinfection among HIV-positive patients, coupled with the development of AIDS, remains a major public health problem. The synergism between the presence of HIV and other viruses has consequences in relation to changes in the severity of the infection, as well as changes in the natural course of both infections. Several polymorphisms present in genes that encode cytokines have a relevant influence on their transcription and consequently on the production of such immunological molecules. The present study evaluated the influence of SNPs located in the promoter regions of genes encoding the cytokines INF-É£, TNF, IL-6, IL-4, and IL-2, as well as their respective plasma concentrations, in patients infected with HIV and/or EBV in the state of Pará. Additionally, this study described the epidemiological profile and compared CD4+ and CD8+ T lymphocyte counts among the groups studied. The associative analysis between the SNPs and plasma cytokine concentrations in different groups showed statistical relevance for three polymorphisms: rs2069762 (IL2), where the GG genotype demonstrated higher IL-2 levels in HIV mono-infected individuals; rs2243250 (IL4), where the CT genotype showed higher IL-4 levels in the control group; and rs2069705 (IFNG), where the TT genotype showed higher IFN-γ levels in the coinfected group. Regarding SNP associations with CD4+/CD8+ counts, significant findings were observed in HIV mono-infected individuals: the rs2069705 (IFNG) polymorphism was linked to higher CD4+ counts with the CT genotype, and rs1799964 (TNF) was associated with higher CD8+ counts with the CC genotype. Therefore, this study provides evidence that the rs2069705 (IFNG) SNP is associated with elevated IFN-γ levels, which may have pathogenic consequences, as depletion of this cytokine is concerning for people living with HIV due to its antiviral properties.

Ceftazidime-Avibactam Use in a Case Series of Difficult-to-Treat or Recurrent Infections in Pediatric Patients with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development.

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections.

Sociobehavioral Risk Factors and Clinical Implications of Late Presentation Among People Living with HIV in the Brazilian Amazon Region.

This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

A novel abbreviated version of the Luria neuropsychological diagnosis battery: reliability and convergent validity in Spanish older adults.

OBJECTIVE: To estimate the test-retest and inter-rater reliability of the new Spanish abbreviated version of the Luria Neuropsychological Diagnosis (DNA-2) battery for older adults. METHOD: A total of thirty cognitively healthy volunteers were examined in this study. The participants completed a comprehensive standardized assessment, encompassing cognitive and functional performance. Intraclass correlation coefficients (ICC) were used to examine test-retest and inter-rater reliability. One month was allowed between administrations. Furthermore, correlations between Luria DNA-2 (total and domain subscores) and other classical cognitive measures were explored. RESULTS: The test-retest reliability on the overall Luria DNA-2 score was high (ICC= .834, 95% CI [.680, .917], p < .001). Furthermore, the inter-rater reliability for the total score demonstrated an excellent concordance between administrators (ICC= .990, 95% CI [.979, .995], p < .001). Positive and significant correlations were observed between Luria DNA-2 (both total and domain subscores) and the Addenbrooke's Cognitive Examination (ACE-III; ρ = .857, p < .001). CONCLUSIONS: This study supports the adequate reliability of the Luria DNA-2, as an abbreviated neuropsychological battery, for assessing cognitive performance in Spaniards aged 55 years and older. Future studies should continue to explore the psychometric properties of the Luria DNA-2, particularly those related to its diagnostic validity for early detection of cognitive impairment.

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region.

Background: Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients. Methods: We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO. Results: The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection. Conclusion: Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

Proprioception and Control of a Soft Pneumatic Actuator Made of a Self-Healable Hydrogel.

The current evolutionary trends in soft robotics try to exploit the capacities of smart materials to achieve compact robotics designs with embodied intelligence. In this way, the number of elements that compose the soft robot can be reduced, as the smart material can cover different aspects (e.g., structure and sensorization) all in one. This work follows this tendency and presents a custom-designed hydrogel that exhibits two smart features, self-healing and ionic conductivity, used to build a pneumatic actuator. The self-healing capability provides the actuator's structure with the ability to self-repair from damages (e.g., punctures or cuts), an important quality to prolong the life cycle of the actuator. The ionic conductivity enables the actuator's proprioception: the structure itself serves as a curvature sensor. The behavior of this proprioceptive curvature sensor is analyzed in this work, studying its linearity, stability, and performance after a self-healing process. This sensor is also proposed as feedback in a closed-loop scheme to automatically control the actuator's curvature. A proportional-integral-derivative controller is designed based on an empirical model of the actuator's dynamics, and then validated in experimental tests, proving the proprioceptive sensor as proper feedback. These control tests are performed over undamaged and self-healed actuators, thus demonstrating all the capabilities of our soft material.

Increase of healthcare-onset Clostridioides difficile infection in adult population since SARS-CoV-2 pandemic: A retrospective cohort study in a tertiary care hospital from 2019 to 2022.

OBJECTIVES: The aim was to assess the impact of the SARS-CoV-2 pandemic on the prevalence, relative incidence (RI), incidence density (ID), ratio of rate incidence (RRI), rate of incidence density (RID), and relative risks (RR) of healthcare-onset Clostridioides difficile infection (HO-CDI) as well as its correlation with the antibiotic consumption. METHODS: Demographic and analytical data of adult patients exhibiting diarrhoea and testing positive for C. difficile were systematically collected from a tertiary care hospital in Madrid (Spain). The periods analysed included: prepandemic (P0), first pandemic-year (P1), and second pandemic-year (P2). We compared global prevalence, RI of HO-CDI per 1,000-admissions, ID of HO-CDI per 10,000-patients-days, RRI, RID, and RR. Antibiotic consumption was obtained by number of defined daily dose per 100 patient-days. RESULTS: In P0, the prevalence of HO-CDI was 7.4% (IC95%: 6.2-8.7); in P1, it increased to 8.7% (IC95%: 7.4-10.1) (p = 0.2), and in P2, it continued to increase to 9.2% (IC95%: 8-10.6) (p < 0.05). During P1, the RRI was 1.5 and RID was 1.4. However, during P2 there was an increase in RRI to 1.6 and RID to 1.6. The RR also reflected the increase in HO-CDI: at P1, the probability of developing HO-CDI was 1.5 times (IC95%: 1.2-1.9) higher than P0, while at P2, this probability increased to 1.6 times (IC95%: 1.3-2.1). There was an increase in prevalence, RI, ID, RR, RRI, and RID during the two postpandemic periods respect to the prepandemic period. During P2, this increase was greater than the P1. Meropenem showed a statistically significant difference increased consumption (p < 0.05) during the pandemic period. Oral vancomycin HO-CDI treatment showed an increase during the period of study (p > 0.05). CONCLUSIONS: Implementation of infection control measures during the SARS-CoV-2 pandemic did not appear to alleviate the burden of HO-CDI. The escalation in HO-CDI cases did not exhibit a correlation with overall antibiotic consumption, except for meropenem.

A Comparison of the Efficacy of Treatment With Fidaxomicin Versus Vancomycin in Clostridioides difficile Infection.

Background Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI.

Agreement between pharmacists and physicians on the assessment of appropriateness of antimicrobial prescribing.

INTRODUCTION: Audits for monitoring the quality of antimicrobial prescribing are a main tool in antimicrobial stewardship programs; however, interobserver reliability has not been conclusively assessed. Our objective was to measure the level of agreement between pharmacists and physicians on the appropriateness of antimicrobials prescribing in hospitals. METHODS: A national multicenter, cross-sectional study was conducted of patients who were receiving antimicrobials one day of April 2021. Hospital participation was voluntary, and the study population was randomly selected. Pharmacists and physicians performed a simultaneous, independent assessment of the quality of antimicrobial prescriptions. The observers used an assessment method by which all indicators of the quality of antimicrobial use were considered. Finally, an algorithm was used to rate overall antimicrobial prescribing as appropriate, suboptimal, inappropriate, or not assessable. Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: In total, 101 hospitals participated, and 411 hospital antimicrobial prescriptions were reviewed. The strength of agreement was moderate regarding the overall quality of prescribing (AC1=0.51; 95%CI=[0.44-0.58]). A very good level of agreement (AC1>0.80) was observed between pharmacists and physicians in all indicators of the quality, except for duration of treatment, rated as good (AC1=0.79; 95%CI=[0.75-0.83]), and registration on the medical record, rated as fair (AC1=0.34; 95%CI=[0.26-0.43]). The agreement was greater in critical care, onco-hematology, and pediatric units than in medical and surgery units. CONCLUSIONS: In this point prevalence study, a moderate level of agreement was observed between pharmacists and physicians in the evaluation of the appropriateness of antimicrobials prescribing in hospitals.

Predictors of the response to phosphodiesterase-5 inhibitors in pulmonary arterial hypertension: an analysis of the Spanish registry.

BACKGROUND: Achieving and maintaining a low-risk profile is associated with favorable outcome in pulmonary arterial hypertension (PAH). The effects of treatment on risk profile are variable among patients. OBJECTIVE: To Identify variables that might predict the response to treatment with phosphodiesterase-5 inhibitors (PDE-5i) in PAH. METHODS: We carried out a cohort analysis of the Spanish PAH registry in 830 patients diagnosed with PAH that started PDE5i treatment and had > 1 year follow-up. 644 patients started PDE-5i either in mono- or add-on therapy and 186 started combined treatment with PDE-5i and endothelin receptor antagonist (ERA). Responders were considered when at 1 year they: (1) were alive; (2) did not present clinical worsening; and (3) improved European Society of Cardiology/European Respiratory Society (ESC/ERS) risk score or remained in low-risk. Univariate and multivariate logistic regression models were used to analyze variables associated with a favorable response. RESULTS: Two hundred and ten patients (33%) starting PDE-5i alone were classified as responders, irrespective of whether it was mono- or add-on therapy. In addition to known predictors of PAH outcome (low-risk at baseline, younger age), male sex and diagnosis of portopulmonary hypertension (PoPH) or HIV-PAH were independent predictors of favorable response to PDE-5i. Diffusing capacity for carbon monoxide (DLco) ≤ 40% of predicted was associated with an unfavorable response. When PDE-5i were used in upfront combination, 58% of patients were responders. In this group, diagnosis of idiopathic PAH (IPAH) was an independent predictor of favorable response, whereas connective tissue disease-PAH was associated with an unfavorable response. CONCLUSION: Male sex and diagnosis of PoPH or HIV-PAH are predictors of favorable effect of PDE-5i on risk profile when used as mono- or add-on therapy. Patients with IPAH respond more favorably to PDE-5i when used in upfront combination. These results identify patient profiles that may respond favorably to PDE-5i in monotherapy and those who might benefit from alternative treatment strategies.

Intestinal loads of extended-spectrum beta-lactamase and Carbapenemase genes in critically ill pediatric patients.

Introduction: Intestinal colonization by Multi-Drug Resistant Organisms (MDROs) can pose a threat on the health of critically ill patients. The extent of colonization by these organisms is related to previous antibiotic treatments and their ability to cause infections among adult patients. The aim of this study is to determine the relationship between the intestinal Relative Loads (RLs) of selected antibiotic resistance genes, antibiotic consumption and extra-intestinal spread among critically ill pediatric patients. Methods: RLs of bla CTX-M-1-Family, bla OXA-1, bla OXA-48 and bla VIM were determined in 382 rectal swabs obtained from 90 pediatric critically ill patients using qPCRs. The RLs were compared to the patients' demographics, antibiotic consumption, and detection of MDROs from extra-intestinal sites. 16SrDNA metagenomic sequencing was performed for 40 samples and clonality analyses were done for representative isolates. Results and discussion: 76 (74.45%) patients from which 340 (89.01%) rectal swabs were collected had at least one swab that was positive for one of the tested genes. Routine cultures did not identify carbapenemases in 32 (45.1%) and 78 (58.2%) swabs that were positive by PCR for bla OXA-48 and blaVIM, respectively. RLs of above 6.5% were associated with extra-intestinal spread of blaOXA-48-harboring MDROs. Consumption of carbapenems, non-carbapenem ß-lactams, and glycopeptides were statistically associated with testing negative for bla CTX-M-1-Family and bla OXA-1 while the consumption of trimethoprim/sulfamethoxazole and aminoglycosides was associated with testing negative for blaOXA-48 (P<0.05). In conclusion, targeted qPCRs can be used to determine the extent of intestinal dominance by antibiotic resistant opportunistic pathogens and their potential to cause extra-intestinal infections among a critically ill pediatric population.

Intestinal obstruction due to pneumatosis intestinalis.

We present the case of an 83-year-old male, with a past medical history of benign pneumoperitoneum secondary to pneumatosis intestinalis which evolved for a number of years with periodic follow-ups. The patient comes to the Emergency Room with sintomatology of intestinal obstruction. Urgent surgical management is decided, an exploratory laparotomy is performed where an intestinal obstruction secondary to pneumatosis intestinalis, with loss of structure of the intestinal wall as visualized in the images, is determined; therefore resection of the affected small intestine segment and primary anastomosis are performed. The pathology report confirms the diagnosis. The patient progresses favorably during the postoperative period and is currently asymptomatic after 12 months.

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice.

BACKGROUND: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. METHODS: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. RESULTS: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. CONCLUSION: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.

Reconstructing secondary data based on air quality, meteorological and traffic data considering spatiotemporal components.

This paper introduces the reconstructed dataset along with procedures to implement air quality prediction, which consists of air quality, meteorological and traffic data over time, and their monitoring stations and measurement points. Given the fact that those monitoring stations and measurement points are located in different places, it is important to incorporate their time series data into a spatiotemporal dimension. The output can be used as input for various predictive analyses, in particular, we used the reconstructed dataset as input for grid-based (Convolutional Long Short-Term Memory and Bidirectional Convolutional Long Short-Term Memory) and graph-based (Attention Temporal Graph Convolutional Network) machine learning algorithms. The raw dataset is obtained from the Open Data portal of the Madrid City Council.

Risk Decision Making and Executive Function among Adolescents and Young Adults.

The dual theory establishes that the decision-making process relies on two different systems, the affective system and the executive function (EF), developed during adolescence. This study analyzes the relationship between the decision-making and EF processes in a group of early adolescents (mean age = 12.51 years, SD = 0.61), where more affective impulse processes are developed, and in young adults (mean age = 19.38 years, SD = 1.97), where cognitive control processes have already matured. For this purpose, 140 participants in Spain completed the Iowa Gambling Task (IGT) to measure their risky decisions and the Wisconsin Card Sorting Task (WCST) to measure their EF. Performance on the IGT improves over blocks; however, adolescents received lower mean scores than young adults. However, controlling for age, perseverative errors were negatively associated with the mean net score on the risky blocks of IGT; thus, those who committed more perseverative errors in the WCST were more likely to take cards from the disadvantageous decks on the last blocks of the IGT. The current study shows that adolescents and adults solve ambiguous decisions by trial and error; however, adolescents are more likely to make risky decisions without attending to the long-term consequences. Following the dual theory hypothesis, the maturation of EF with age partly accounts for this difference in risky decision-making between adolescents and adults.