Recent Advances in Nanodrug Delivery Systems Production, Efficacy, Safety, and Toxicity.

In the last three decades, the development of nanoparticles or nano-formulations as drug delivery systems has emerged as a promising tool to overcome the limitations of conventional delivery, potentially to improve the stability and solubility of active molecules, promote their transport across the biological membranes, and prolong circulation times to increase efficacy of a therapy. Despite several nano-formulations having applications in drug delivery, some issues concerning their safety and toxicity are still debated. This chapter describes the recent available information regarding safety, toxicity, and efficacy of nano-formulations for drug delivery. Several key factors can influence the behavior of nanoparticles in a biological environment, and their evaluation is crucial to design non-toxic and effective nano-formulations. Among them, we have focused our attention on materials and methods for their preparation (including the innovative microfluidic technique), mechanisms of interactions with biological systems, purification of nanoparticles, manufacture impurities, and nano-stability. This chapter places emphasis on the utilization of in silico, in vitro, and in vivo models for the assessment and prediction of toxicity associated with these nano-formulations. Furthermore, the chapter includes specific examples of in vitro and in vivo studies conducted on nanoparticles, illustrating their application in this field.

Tecnologias em saúde da hanseníase no âmbito da Atenção Primária à Saúde: revisão de escopo / Leprosy health technologies in Primary Health Care: a scoping review / Tecnologías en salud de la lepra en el ámbito de la Atención Primaria a la Salud: revisión del alcance

Objetivo: mapear as tecnologias em saúde para manejo no cuidado à pessoa com hanseníase na Atenção Primária à Saúde. Método: revisão de escopo baseada na metodologia do JBI, em seis bases de dados, seguindo a checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Foram incluídos estudos publicados em qualquer idioma, com diferentes abordagens metodológicas. Resultados: os 14 estudos incluídos na revisão mostram que a aplicabilidade de tecnologias para o manejo do cuidado a pessoa com hanseníase na Atenção Primária à Saúde, possibilitam a confirmação de diagnóstico, acompanhamento, monitoramento e prevenção de incapacidades. Conclusão: nota-se que tecnologia em saúde se apresentam como ferramentas que auxiliam no processo de cuidado na assistência a pessoas com hanseníase, a fim de permitir aos profissionais de saúde conhecimento sobre a doença, proporcionando qualidade na sua prática de saúde.

Objective: to map health technologies for managing the care of people with leprosy in Primary Health Care. Method: scoping review based on the JBI methodology in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Studies published in any language were included, with different methodological approaches. Results: the 14 studies included in the review show that the applicability of technologies for the management of care for people with leprosy in Primary Health Care makes it possible to confirm diagnosis, follow-up, monitoring, and prevention of disabilities. Conclusion: it has been noted that health technologies are tools that help in the process of caring for people with leprosy, to provide health professionals with knowledge about the disease, improving quality of health practice.

Objetivo: mapear las tecnologías en salud para el manejo en el cuidado a la persona con lepra en la Atención Primaria a la Salud. Método: revisión del alcance basada en la metodología del JBI, en seis bases de datos, siguiendo la checklist Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Se han incluido estudios publicados en cualquier idioma, con diferentes enfoques metodológicos. Resultados: los 14 estudios incluidos en la revisión muestran que la aplicabilidad de tecnologías para el manejo del cuidado a la persona con lepra en la Atención Primaria a la Salud posibilita la confirmación de diagnóstico, seguimiento, monitoreo y prevención de incapacidades. Conclusión: se percibe que las tecnologías en salud se presentan como herramientas que ayudan en el proceso de cuidado en la asistencia a personas con lepra, con fines de permitir a los profesionales de salud el acceso al conocimiento sobre la enfermedad, proporcionando calidad en su práctica de salud.

A Comprehensive Assessment of the Environmental Impact of Different Infant Feeding Types: The Observational Study GREEN MOTHER.

AIM(S): To observe and compare the environmental impacts of different types of infant feeding, considering the use of formula, infant feeding accessories, potentially increased maternal dietary intake during breastfeeding (BF) and food consumption habits. DESIGN: An observational cross-sectional multicentre study conducted in the Barcelona Metropolitan Area of the Catalan Institute of Health. METHODS: Data were collected from 419 postpartum women on infant feeding type (formula milk and accessories), maternal dietary intake (24-h register) and food consumption habits from November 2022 to April 2023. The environmental impacts (climate change (CC), water consumption and water scarcity) of the infant feeding types and maternal diet were calculated using the IPCC, ReCiPE and AWARE indicators, respectively. The differences in impacts were calculated by Kruskal-Wallis test. RESULTS: Significant differences for the three environmental impacts were observed. The CC impact of formula milk and feeding accessories was 0.01 kg CO2eq for exclusive BF, 1.55 kg CO2eq for mixed feeding and 4.98 kg CO2eq for formula feeding. While BF mothers consumed an extra 238 kcal, no significant differences were found related to maternal diet across feeding types. CONCLUSION: Exclusive BF was the most sustainable type of infant feeding, considering formula and infant feeding accessories. In our study, the difference between the impacts of BF and non-BF mothers' diet was insignificant. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Offer informative and educational support for midwives and other healthcare professionals on BF and a healthy, sustainable diet to transfer this knowledge to the general public. IMPACT: Raise the general public's awareness about BF and a healthy, sustainable diet. To reduce environmental impacts through behavioural changes. REPORTING METHOD: STROBE. PATIENT OR PUBLIC CONTRIBUTION: Patients of the Catalan Health Service reviewed the content of the data collection tools. TRIAL REGISTRATION: (for the whole GREEN MOTHER project): NCT05729581 (https://clinicaltrials.gov).

Unravelling the role of secretory Immnuoglobulin-A in COVID-19: a multicentre study in nursing homes during the first wave.

BACKGROUND: The function of mucosal secretory IgA (SIgA) seems to be paramount in the immune response against SARS-CoV-2 however, there are few studies addressing this issue specifically in the institutionalized older population. This study aims to determine the levels of secretory IgA against the S1 domain of the SARS-CoV-2 spike (SIgA-S1) in older people living in nursing homes (NH) and to investigate the differences in baseline characteristics, severity of COVID-19, duration of symptoms, 30-day mortality, and reinfection according to the levels of SIgA-S1. METHODS: In this multicentre longitudinal study, conducted in two NHs attended in coordination with a hospital-based Geriatric team, 305 residents (87.3 years, 74.4% female) were included. A massive collection of nasopharyngeal samples was carried out after the first wave of COVID-19 in May 2020 and an ELISA analysis of SIgA-S1 was performed on frozen samples in May 2023. Values of SIgA-S1 ≥ 57.6 U/mL ("cut-off point") were considered "induced". Resident medical records were reviewed to assess symptoms, comprehensive geriatric assessment (CGA), reinfection, and overall 30-day mortality. RESULTS: At the time of sample collection, 274 residents (89.8%) exhibited "induced" SIgA-S1 levels (≥ 57.6 U/mL), 46 (15.1%) tested positive for PCR SARS-CoV-2, and 170 (57%) had experienced COVID-19 symptoms. "Induced" SIgA-S1 patients were more likely to be symptomatic (60.3% vs. 29%; p < 0.001) and exhibited upper respiratory tract symptoms more frequently (25.1% vs. 6.5%; p = 0.020) compared to "non-induced" patients. Patients with severe disease and duration of symptoms > 10 days had higher levels of SIgA-S1 than those with mild disease (252 vs.192.6 U/mL; p = 0.012) or duration ≤ 10 days (270.5 vs. 208.1 U/mL; p = 0.043), respectively. No significant differences were observed in age, sex, CGA, duration of symptoms, disease severity, overall 30-day-mortality, or reinfection between "induced" and "non-induced" residents. CONCLUSIONS: Levels of SIgA-S1 are associated with the duration and type of COVID-19 symptoms, along with the severity of infection. While these findings shed light on the knowledge of SIgA-S1, further interdisciplinary studies are warranted to better understand the immune response to SARS-CoV-2 infection.

BRCA1 levels and DNA-damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA.

Circular RNAs (circRNAs) are covalently closed RNA molecules widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Many studies point to their activity as microRNAs (miRNAs) and protein sponges; however, we propose a function based on circRNA-mRNA interaction to regulate mRNA fate. We show that the widely tumor-associated circHIPK3 directly interacts in vivo with the BRCA1 mRNA through the back-splicing region in human cancer cells. This interaction increases BRCA1 translation by competing for the binding of the fragile-X mental retardation 1 protein (FMRP) protein, which we identified as a BRCA1 translational repressor. CircHIPK3 depletion or disruption of the circRNA-mRNA interaction decreases BRCA1 protein levels and increases DNA damage, sensitizing several cancer cells to DNA-damage-inducing agents and rendering them susceptible to synthetic lethality. Additionally, blocking FMRP interaction with BRCA1 mRNA with locked nucleic acid (LNA) restores physiological protein levels in BRCA1 hemizygous breast cancer cells, underscoring the importance of this circRNA-mRNA interaction in regulating DNA-damage response.

Aztreonam-avibactam versus meropenem for the treatment of serious infections caused by Gram-negative bacteria (REVISIT): a descriptive, multinational, open-label, phase 3, randomised trial.

BACKGROUND: There is a need for additional therapeutic options for serious infections caused by Gram-negative pathogens. In the phase 3, descriptive REVISIT study, we investigated the safety and efficacy of aztreonam-avibactam in the treatment of complicated intra-abdominal infections or hospital-acquired pneumonia or ventilator-associated pneumonia (HAP-VAP) caused, or suspected to be caused, by Gram-negative bacteria. METHODS: This prospective, multinational, open-label, central assessor-masked study enrolled adults who were hospitalised with a complicated intra-abdominal infection or HAP-VAP. Patients were randomly allocated via block randomisation using interactive response technology stratified by infection type in a 2:1 ratio to aztreonam-avibactam (with metronidazole for complicated intra-abdominal infection) or meropenem with or without colistin for 5-14 days for complicated intra-abdominal infection or 7-14 days for HAP-VAP. The primary endpoint was clinical cure at the test-of-cure visit (within 3 days before or after day 28) in the intention-to-treat (ITT) population. Secondary endpoints included 28-day mortality in the ITT population and safety in patients in the ITT population who received study drug (safety analysis set). No formal hypothesis testing was planned. The study was registered with ClinicalTrials.gov (NCT03329092) and EudraCT (2017-002742-68) and is complete. FINDINGS: Between April 5, 2018, and Feb 23, 2023, we screened 461 patients. 422 patients were enrolled and randomly allocated (282 in the aztreonam-avibactam group and 140 in the meropenem group, forming the ITT analysis set), of whom ten patients (seven in the aztreonam-avibactam group and three in the meropenem group) were randomly allocated but did not receive study treatment. 271 (64%) of 422 patients had at least one Gram-negative pathogen from an adequate specimen identified at baseline. The most frequent baseline pathogens were Enterobacterales (252 [93%] of 271). Overall, 19 (24%) of 80 isolates tested for carbapenemases were carbapenemase-positive (serine, metallo-ß-lactamase, or both). 193 (68·4%) of 282 patients in the aztreonam-avibactam group and 92 (65·7%) of 140 in the meropenem group had clinical cure at the test-of-cure visit (treatment difference 2·7% [95% CI -6·6 to 12·4]). For patients with complicated intra-abdominal infection, the adjudicated clinical cure rate was 76·4% (159 of 208) for the aztreonam-avibactam group and 74·0% (77 of 104) for the meropenem group. Cure rates in patients with HAP-VAP were 45·9% (34 of 74) for aztreonam-avibactam and 41·7% (15 of 36) for meropenem. 28-day all-cause mortality rates were 4% (12 of 282) for aztreonam-avibactam and 7% (ten of 140) for meropenem; in patients with complicated intra-abdominal infection, mortality was 2% (four of 208) and 3% (three of 104) for aztreonam-avibactam and meropenem, respectively, and in patients with HAP-VAP, mortality was 11% (eight of 74) and 19% (seven of 36), respectively. Aztreonam-avibactam was generally well tolerated, and safety findings were consistent with the known safety profile of aztreonam monotherapy. There were no treatment-related serious adverse events in the aztreonam-avibactam group. INTERPRETATION: These phase 3 efficacy and safety data provide support for aztreonam-avibactam as a potential therapeutic option for complicated intra-abdominal infection or HAP-VAP caused by Gram-negative bacteria. FUNDING: Pfizer.

Respiratory and allergic outcomes among farmworkers exposed to pesticides in Costa Rica.

AIM: We examined the association of exposure to a pesticide mixture with respiratory and allergic outcomes among farmworkers from Costa Rica. METHODS: We conducted a cross-sectional study of 299 farmworkers between May and August 2016. We collected information on sociodemographic factors, pesticide use, and the presence of respiratory and allergic symptoms during the last 12 months via questionnaire. We calculated specific gravity-adjusted average concentrations of 15 pesticide biomarkers measured in urine samples collected during two visits (4-5 weeks apart). We fitted "traditional" Bayesian and Bayesian Weighted Quantile Sum (BWQS) regression models to assess the association of exposure to independent and summed pesticide mixture components with the outcomes of interest. We adjusted all models for age and smoking status. RESULTS: In "traditional" Bayesian analyses, higher urinary concentrations of 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPY, metabolite of organophosphate insecticide diazinon) were associated with increased odds of a higher asthma symptom score [adjusted OR per two-fold increase in concentrations = 1.15; 95 % credible interval (CrI): 1.04, 1.27)], asthma symptoms or medication use (aOR = 1.37; 95 % CrI: 1.13, 1.67), and rhinitis (aOR = 1.34; 95 % CrI: 1.15, 1.56). Higher urinary concentrations of boscalid-5-hydroxy (metabolite of fungicide boscalid) were associated with increased odds of asthma symptoms or medication use (aOR = 1.24; 95 % CrI: 1.00, 1.55), whereas higher concentrations of 4-hydroxypyrimethanil (metabolite of the fungicide pyrimethanil) were associated with increased odds of eczema (aOR = 1.11; 95 % CrI: 0.99, 1.24). Several inverse associations of herbicide concentrations with respiratory and allergic outcomes were observed. In BWQS analyses, a positive association was found between exposure to the pesticide mixture and increased odds of rhinitis (aOR = 1.96; 95 % CrI: 1.14, 3.20), with IMPY being the largest contributor. CONCLUSION: Our findings indicate that exposure to pesticides may have both independent and summed mixture effects on respiratory and allergic health among farmworkers.

Reference equations for pulse wave velocity, augmentation index, amplitude of forward and backward wave in a European general adult population.

Pulsatile hemodynamics have been shown to be independent predictors of cardiovascular events. The aim of the current study was to describe four pulsatile hemodynamic markers in a large, well-established, population-based cohort and to provide reference equations for sex- and age-based standardization of these measurements. 6828 adult participants from the Austrian LEAD (Lung, hEart, sociAl, boDy) cohort study, who were free from overt cardiovascular disease, non-diabetic based on blood test results, and had no history of pharmacological treatment for hypertension, dyslipidemia, and diabetes, comprised the "reference population". Carotid-femoral pulse wave velocity (cfPWV), augmentation index (AIx), amplitude of forward wave (Pf), and backward wave (Pb) were described in different age categories for both sexes. Sex-specific reference equations for cfPWV, AIx, Pf, and Pb with age as the predictive variable were created using the Lambda-Mu-Sigma (LMS) method. All four parameters increased with age. CfPWV and Pf were higher in males than females, especially in young and middle-age groups (P < 0.001). AIx was higher in females than males in all age categories (P < 0.001). Pb was also higher in females than males in age groups older than 40 years (P < 0.01). Reference equations for the skewness (Lambda), median (Mu), and coefficient of variation (Sigma) values were determined, enabling the calculation of sex- and age-standardized values (z-scores) for each individual's pulsatile hemodynamic measurement, and an online application was developed. Reference equations derived from a large population-based dataset constitute a suitable tool for the standardization of pulsatile hemodynamics and for the accurate interpretation of vascular aging.

Efficacy of the Otago-Exercise-Programme to reduce falls in community-dwelling adults aged 65-80 when delivered as group or individual training: Non-inferiority-clinical-trial.

BACKGROUND: The Otago Exercise Programme is an effective intervention for falls prevention. However, there is limited evidence in relation to studies that compare efficacy for falls prevention when delivered Otago Exercise Programme in a group or individual format in a primary care context. OBJECTIVE: To compare the Otago Exercise Programme delivered as a group vs. individual format for community dwelling older adults, over a one year period. The hypothesis was that neither format would be inferior to the other. METHODS: DESIGN: A four-year multicentre, randomized, non-inferiority clinical trial, with two arms- Otago Exercise Programme group training and individual Otago exercise training. SETTING(S): 21 primary healthcare centers. PARTICIPANTS: A sample size of 728 participants was established. Participants were aged between 65 and 80 years; living in the community; able to walk independently; and agreed to take part in the study and provided signed informed consent. INTERVENTION: The Otago Exercise Programme was delivered mainly by nurses in primary care, with five face to face sessions, and a reinforcement 6 months later. Participants were encouraged to exercise at home between face to face sessions. DATA COLLECTION: at baseline and after 6 and 12 months from October 2017 to 2020. PRIMARY OUTCOME: people who reported at least one fall. SECONDARY OUTCOMES: number of falls, cause of falls, consequences and assistance, adherence and satisfaction. Group allocation was blinded to the researchers involved in analysis. Reporting: Consolidated Standards of Reporting Trials recommendations for the Statement for Randomized Trials of Nonpharmacologic Treatments. RESULTS: Eight hundred twenty-seven participants were randomized (226 were allocated in group training and 272 in individual training). The analysis of the proportion of people who reported at least one fall and number of falls showed no differences between individual and group training. Assessment of the equivalence between the interventions at 12 months showed that the confidence interval for the difference of people who reported at least one fall was found to be within the equivalence limit of 10% considered. However, in those participants with a previous history of falls, group format showed potentially greater benefit. The participants in individual training presented higher scores on the Exercise Adherence Rating Scale test. No differences were found in satisfaction between the groups. CONCLUSIONS: The group Otago Exercise Programme is equivalent to individually delivered Otago Exercise Programme in terms of prevention of falls over a 12-month follow up. Adherence was higher in individual training. IMPLICATIONS: Healthcare professionals could offer either Otago Exercise Programme format dependent on patient preference and be confident that that standardized intervention provides patient benefit. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03320668). Data registration 31/10/2017.

Influence of free and microencapsulated recombinant rabbit nerve growth factor with chitosan on rabbit sperm quality parameters.

ß-nerve growth factor (ßNGF) plays a crucial role in reproductive physiology and sperm quality. Enzymatic activity of seminal plasma and vaginal fluids reduces available ßNGF and it has been demonstrated that chitosan microspheres could protect rrßNGF from degradation. This study examined the effects of microencapsulated rrbNGF with chitosan on rabbit sperm viability, motility and capacitation status. Results showed that 0.5 and 1 µg/mL of microencapsulated rrßNGF, as well as free rrßNGF or empty microspheres, did not adversely affect sperm viability or total motility after 2 h of incubation. However, the highest progressivity kinetic parameters were observed with 1 µg/mL free rrßNGF, while the highest curvilinear velocity (VCL) occurred with 0.5 µg/mL microencapsulated rrßNGF. Empty chitosan microspheres did not induce acrosome reaction (AR), but both concentrations of free and rrßNGFch favoured AR during in vitro incubation. The study suggests that using chitosan spheres did not show any adverse effects on sperm traits, unlike free rßNGF and rrßNGFch promoted capacitation and AR. Further research is needed to explore the potential of rrßNGFch in modifying in vitro capacitation and inducing ovulation during artificial insemination.

Systemic amyloidosis: an aggressive evolution in a patient with relapsing polychondritis and monoclonal gammopathy of undetermined significance (MGUS) undergoing peritoneal dialysis.

Herein, we report the case of primary amyloidosis with multi-organ involvement in a female patient in her 50s. The patient had a history of relapsing polychondritis, chronic kidney disease, and monoclonal gammopathy of undetermined significance (MGUS). The clinical manifestations included neuropathic pain, sensorimotor polyneuropathy, intrahepatic cholestatic liver injury, gastrointestinal symptoms, dysautonomia, and myocardial thickening. Initial histologic evaluations of the abdominal fat pad aspirate and bone marrow biopsy were negative for amyloid deposition. However, due to a high index of suspicion, a second bone marrow biopsy was performed, confirming the presence of the amyloid protein. Given the patient's complex medical history, other types of amyloidosis, such as AA amyloidosis, AL amyloidosis, and ß2-microglobulin amyloidosis, should also be considered as differential diagnoses. The type of amyloid protein was subsequently identified through laser microdissection of amyloid fibrils followed by liquid chromatography-tandem mass spectrometry as AL-lambda (amyloid light-chain) amyloidosis. The patient presented unfavorable evolution, with progressive dysautonomia, being admitted to the ICU, culminating in refractory circulatory shock, and undergoing an empirical broad-spectrum antibiotic therapy. After a few days, she presented pulseless ventricular tachycardia, culminating in her death, before undergoing specific treatment. This article highlights the crucial role of precise identification in guiding appropriate therapeutic strategies for this complex, yet potentially severe, diseases.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Exercise and brain health in patients with coronary artery disease: study protocol for the HEART-BRAIN randomized controlled trial.

Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group-usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. Clinical trial registration: ClinicalTrials.gov, identifier [NCT06214624].

Induced abortion incidence and associated factors in a cohort of women living with HIV in Rio De Janeiro, Brazil, 1996-2016.

BACKGROUND: Abortion is a public health problem in Latin America and is more common among women living with HIV. OBJECTIVE: to verify the incidence and factors associated with induced abortion in a cohort of women living with HIV assisted in a reference service for care for individuals with HIV/AIDS in Rio de Janeiro/Brazil. METHODS: Prospective cohort during the period 1996-2016. We estimated the incidence of induced abortions during follow-up in the cohort by calculating person-time incidence rates [per 100 persons-years (PY)] and investigated the factors associated with the outcome "induced abortion" using a generalized linear mixed model. RESULTS: 753 women and 210 pregnancies were included in the present analysis. We estimated an induced abortion incidence rate of 0.68/100 persons-years (95% confidence interval [CI]: 0.47; 0.94) in the study period, with a significant reduction after 2006. The main factors associated with an induced abortion were currently living with a partner (adjusted OR [AdjOR] 0.32 95% CI: 0.10-0.98), number of children (2 children AdjOR 0.12, 95% CI: 0.02-0.95) and the type of antiretroviral treatment used (regimen without Efavirenz: AdjOR: 0.11, 95% CI 0.02-0.70). CONCLUSIONS: We showed a significant reduction in the incidence of induced abortions in a cohort of women living with HIV in Rio de Janeiro, Brazil, probably due to a decrease in the incidence of pregnancies observed in the same period. The factors associated with a lower occurrence of induced abortion suggest a good integration between the clinical and reproductive assistance offered to those women.

Structural connectivity modifications following deep brain stimulation of the subcallosal cingulate and nucleus accumbens in severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is a mental health disorder characterized by significant weight loss and associated medical and psychological comorbidities. Conventional treatments for severe AN have shown limited effectiveness, leading to the exploration of novel interventional strategies, including deep brain stimulation (DBS). However, the neural mechanisms driving DBS interventions, particularly in psychiatric conditions, remain uncertain. This study aims to address this knowledge gap by examining changes in structural connectivity in patients with severe AN before and after DBS. METHODS: Sixteen participants, including eight patients with AN and eight controls, underwent baseline T1-weigthed and diffusion tensor imaging (DTI) acquisitions. Patients received DBS targeting either the subcallosal cingulate (DBS-SCC, N = 4) or the nucleus accumbens (DBS-NAcc, N = 4) based on psychiatric comorbidities and AN subtype. Post-DBS neuroimaging evaluation was conducted in four patients. Data analyses were performed to compare structural connectivity between patients and controls and to assess connectivity changes after DBS intervention. RESULTS: Baseline findings revealed that structural connectivity is significantly reduced in patients with AN compared to controls, mainly regarding callosal and subcallosal white matter (WM) tracts. Furthermore, pre- vs. post-DBS analyses in AN identified a specific increase after the intervention in two WM tracts: the anterior thalamic radiation and the superior longitudinal fasciculus-parietal bundle. CONCLUSIONS: This study supports that structural connectivity is highly compromised in severe AN. Moreover, this investigation preliminarily reveals that after DBS of the SCC and NAcc in severe AN, there are WM modifications. These microstructural plasticity adaptations may signify a mechanistic underpinning of DBS in this psychiatric disorder.

Wastewater-based epidemiology to assess pharmaceutical consumption. Spanish perspective.

Wastewater-based epidemiology (WBE) is a well-established approach that can provide objective and real-time data on the consumption of substances such as pharmaceuticals. However, most of the studies reported so far compares consumption data obtained using WBE with those derived from prescription data from public health systems, which is often incomplete and might represent a source of uncertainty. This study aims to compare the measured pharmaceutical consumption back calculated with the WBE approach with consumption derived from dispensed pharmaceuticals in two regions of Spain, managed by two different Health Systems. To do so, a group of 17 pharmaceuticals, including the most representative ones of every therapeutic family, were monitored in influent wastewater (IWW) samples collected over a week campaign in spring 2022 at four different wastewater treatment plants (WWTPs) in Spain: two WWTPs in Madrid city (center of Spain) and two WWTPs in Catalonia (Northeast of Spain). Population-normalized daily loads (PNDL) revealed that the patterns of pharmaceutical occurrence in the different WWTPs are very similar, being acetaminophen, 4-acetamidoantipyrine and valsartan the pharmaceuticals with the highest PNDL values: 17162 ± 1457 mg day-1 1000 inh-1 for acetaminophen, 2365 ± 696 and 2429 ± 263 mg day-1 1000 inh-1 for 4-acetamidoantipyrine, 2006 ± 541 and 2041 ± 352 mg day-1 1000 inh-1 for valsartan. Pharmaceutical PNLDs were then transformed into measured pharmaceutical consumption (MC) and compared with dispensed consumption (DC) data obtained from the pharmacies in the catchment area where the WWTPs are located. A ratio MC/DC within 0.8 to 1.2 was obtained for 11 out of the 17 studied pharmaceuticals. Highlighting a match in all the cardiovascular system pharmaceuticals, with the exception of losartan (1.29-1.39 ratio) and valsartan (1.35-1.43) in all WWTPs. In summary, the degree of correlation between MC/DC is higher than those previously reported comparing with the prescribed pharmaceutical consumption.

The Impact of the Coronavirus Disease 2019 Pandemic on Helicopter Emergency Medical Services.

The coronavirus disease 2019 pandemic has profoundly affected the Lombardy healthcare system. Although air transport of critical patients played a crucial role, there are still gaps in understanding how the pandemic impacted helicopter emergency medical services (HEMS). A retrospective observational analysis was performed using data from the regional emergency-urgency online portal. The investigation focused on patients airlifted by helicopter to the Lombardy emergency departments from January 1, 2019, to December 31, 2021. A total of 12,953 admissions to the emergency departments have been recorded (5,733 in 2019, 3,550 in 2020, and 3,670 in 2021). The monthly average of events changed significantly over the 3 years (2019 [477.7], 2020 [295.8], and 2021 [305.8]) (P < .001). Additionally, there was a notable increase in the percentage of severe cases with red triage codes in 2020 (28.9%) and 2021 (33.5%) compared with 2019 (19.9%). Moreover, the number of hospitalized patients increased in 2020 (39.9%) and 2021 (37.2%) compared with 2019 (27.7%). The HEMS documented a noteworthy decrease in mission numbers and an increase in patient clinical severity during the pandemic. Consequently, the HEMS might be allocated for specific roles in national pandemic plans during the alert phase activation, such as secondary transport between hospital facilities.

Internet addiction, sleeping habits and psychological distress in Brazilian adolescents and young adults.

BACKGROUND: The internet is widespread in modern society and has raised concerns about excessive usage and its consequences for different aging groups. OBJECTIVE: This study explores the relationships between internet addiction, sleep patterns, and psychological distress in adolescents and young adults. MATERIALS AND METHODS: In order to assess this phenomenon, an exploratory cross-sectional study was conducted in southern Brazil from October to December 2023. A questionnaire, administered via Google Forms, collected data from 618 participants aged 15-36. The participants consisted of a non-probabilistic community sample selected based on convenience criteria. Instruments included a sociodemographic questionnaire, the Internet Addiction Test, Depression, Anxiety, and Stress Scale, and Social Media Engagement Questionnaire. RESULTS: It was categorized 48.1% as having moderate internet addiction, and classified 0.8% as having severe internet addiction. Correlation analysis revealed positive associations between internet addiction and depression, anxiety, and stress. Logistic regression identified internet addiction and overall psychological distress as predictors of sleep difficulties, along with unemployment status. The findings highlight the detrimental impact of excessive internet use on sleep quality and mental health. The bidirectional relationship between internet addiction and psychological distress underscores the complex interplay between these variables. CONCLUSIONS: This study underscores the urgent need for interventions targeting internet addiction and its associated consequences in adolescents and young adults. Addressing internet addiction levels and promoting healthy internet usage habits are crucial steps in mitigating the adverse effects on mental health and sleep quality. There is a need for targeted interventions, protocols, and preventive measures to mitigate the adverse effects of excessive internet use on mental health and sleep quality. Public health strategies should include IA and its consequences in health programs with multidisciplinary approaches and protocols for treatments for behavioral addictions. The study emphasizes the multifaceted nature of internet addiction and its implications for mental health and sleep patterns.

Phytochemical Study of Stachys iva Griseb. and In Vitro Evaluation of AhR Transcriptional Activity.

Genus Stachys L. consists of approximately 365 species, distributed mainly in temperate regions. Several members of this genus are widely used in the traditional medicine of different countries worldwide. In Greece, 54 Stachys taxa are found in parts of the mainland and/or insular country. The present study focused on the phytochemical investigation of Stachys iva Griseb. and the in vitro anti-inflammatory evaluation of the isolated compounds. In total, eighteen compounds were isolated and identified from the dichloromethane-methanol extract, belonging to iridoids, flavonoids, phenylethanoid glycosides, and phenolic acids. An in vitro approach assessed the aryl hydrocarbon receptor (AhR) modulatory effects of these compounds, revealing an AhR agonistic activity of the flavonoid aglycones apigenin and cirsimaritin in HepG2 and HT29 cell lines. The present study contributes to the evidence of the traditional uses of Stachys spp. and its bioactive constituents, justifying the ethnopharmacological use as an anti-inflammatory plant genus.

MicroRNA dysregulation in ataxia telangiectasia.

Introduction: Ataxia telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, a predisposition to malignancies, and high clinical variability. Profiling of microRNAs (miRNAs) may offer insights into the underlying mechanisms of complex rare human diseases, as miRNAs play a role in various biological functions including proliferation, differentiation, and DNA repair. In this study, we investigate the differential expression of miRNAs in samples from AT patients to identify miRNA patterns and analyze how these patterns are related to the disease. Methods: We enrolled 20 AT patients (mean age 17.7 ± 9.6 years old) and collected clinical and genetic data. We performed short non-coding RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and fibroblasts to compare the miRNA expression profile between AT patients and controls. Results: We observed 42 differentially expressed (DE)-miRNAs in blood samples and 26 in fibroblast samples. Among these, three DE-miRNAs, miR-342-3p, miR-30a-5p, and miR-195-5p, were further validated in additional AT samples, confirming their dysregulation. Discussion: We identified an AT-related miRNA signature in blood cells and fibroblast samples collected from a group of AT patients. We also predicted several dysregulated pathways, primarily related to cancer, immune system control, or inflammatory processes. The findings suggest that miRNAs may provide insights into the pathophysiology and tumorigenesis of AT and have the potential to serve as useful biomarkers in cancer research.