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1.
J Clin Invest ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38870029

ABSTRACT

Leigh syndrome is the most common inherited mitochondrial disease in children and is often fatal within the first few years of life. In 2020, mutations in the gene encoding sulfide:quinone oxidoreductase (SQOR), a mitochondrial protein, were identified as a cause of Leigh syndrome. Here, we report that mice with a mutation in the gene encoding SQOR (SqorΔN/ΔN mice), which prevented SQOR from entering mitochondria, had clinical and pathological manifestations of Leigh syndrome. SqorΔN/ΔN mice had increased blood lactate levels that were associated with markedly decreased complex IV activity and increased hydrogens sulfide (H2S) levels. Because H2S is produced by both gut microbiota and host tissue, we tested whether metronidazole (a broad-spectrum antibiotic) or a sulfur-restricted diet rescues SqorΔN/ΔN mice from developing Leigh syndrome. Daily treatment with metronidazole alleviated increased H2S levels, normalized complex IV activity and blood lactate levels, and prolonged the survival of SqorΔN/ΔN mice. Similarly, a sulfur-restricted diet normalized blood lactate levels and inhibited the development of Leigh syndrome. Taken together, these observations suggest that mitochondrial SQOR is essential to prevent systemic accumulation of H2S. Administration of metronidazole or a sulfur-restricted diet may be therapeutic approaches to treatment of patients with Leigh syndrome caused by mutations in SQOR.

2.
Genes (Basel) ; 15(5)2024 05 04.
Article in English | MEDLINE | ID: mdl-38790214

ABSTRACT

Large-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain), utilizing whole genome sequencing data from 358 unrelated individuals of Spanish origin. Our analysis revealed 61,410 biallelic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1069 SNVs as common in Navarre. In conclusion, this study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.


Subject(s)
Gene Frequency , Polymorphism, Single Nucleotide , Humans , Spain , Polymorphism, Single Nucleotide/genetics , Whole Genome Sequencing , Male , Female , Genetics, Population , Genetic Variation , Genome, Human , Exome/genetics , Cohort Studies
3.
Epileptic Disord ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780451

ABSTRACT

Pathogenic variants in CACNA1E are associated with early-onset epileptic and developmental encephalopathy (DEE). Severe to profound global developmental delay, early-onset refractory seizures, severe hypotonia, and macrocephaly are the main clinical features. Patients harboring the recurrent CACNA1E variant p.(Gly352Arg) typically present with the combination of early-onset DEE, dystonia/dyskinesia, and contractures. We describe a 2-year-and-11-month-old girl carrying the p.(Gly352Arg) CACNA1E variant. She has a severe DEE with very frequent drug-resistant seizures, profound hypotonia, and episodes of dystonia and dyskinesia. Long-term video-EEG-monitoring documented subsequent tonic asymmetric seizures during wakefulness and mild paroxysmal dyskinesias of the trunk out of sleep which were thought to be a movement disorder and instead turned out to be focal hyperkinetic seizures. This is the first documented description of the EEG findings in this disorder. Our report highlights a possible overlap between cortical and subcortical phenomena in CACNA1E-DEE. We also underline how a careful electro-clinical evaluation might be necessary for a correct discernment between the two disorders, playing a fundamental role in the clinical assessment and proper management of children with CACNA1E-DEE.

4.
Drug Alcohol Depend ; 260: 111322, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38728924

ABSTRACT

Sweet foods activate the reward system that is essential in processing natural reinforcers. Maturation changes in this system during adolescence are linked to heightened impulsivity and risk-seeking behavior, including the use of drugs like ethanol. This usually starts with the consumption of sugary mixtures. However, the influence of sugar exposure on ethanol consumption remains inconclusive. The present research examines the effect of long-term sugar exposure on sugary ethanol (S-EtOH) preference and net intake, exploring the implications of sex, age, accessor restriction of sugar, and its effect during the transition into adulthood. Wistar rats of both sexes were given 24-hour access to a sugar solution for 21 days during adolescence or adulthood. Subsequently, four preference tests of S-EtOH vs. water were carried out every other day, with or without sugar access between each preference test. Our results demonstrate that continuous acute and long-term sugar access induces a consummatory suppression effect on S-EtOH intake, particularly in adult rats, irrespective of sex. This effect becomes more pronounced with more extended periods of exposure to sugar, leading to a higher prevalence of low consumers. Notably, when sugar access was restricted after high familiarization, the suppression effect in adolescent male rats was reduced. Under these conditions, the rats appeared to be more susceptible to developing a preference for S-EtOH consumption. Furthermore, our longitudinal observations reveal that sugar access or restriction conditions during the transition from adolescence to adulthood play a crucial role in shaping S-EtOH consumption patterns in adulthood.


Subject(s)
Alcohol Drinking , Ethanol , Rats, Wistar , Animals , Male , Female , Rats , Ethanol/pharmacology , Ethanol/administration & dosage , Alcohol Drinking/psychology , Sex Characteristics , Age Factors , Consummatory Behavior/drug effects , Aging/drug effects
5.
An. pediatr. (2003. Ed. impr.) ; 100(4): 268-274, abril 2024. ilus
Article in Spanish | IBECS | ID: ibc-232097

ABSTRACT

Durante el embarazo, los cambios fisiológicos en la respuesta inmunitaria favorecen que las gestantes sean más susceptibles a infecciones graves, tanto para ellas como para el feto, el recién nacido y el lactante. Todas las mujeres deberían entrar en el período reproductivo con su calendario vacunal correctamente cumplimentado, sobre todo en lo que respecta a enfermedades como tétanos, hepatitisB, sarampión, rubeola y varicela. Además de las vacunas recomendadas, en situaciones de riesgo las vacunas inactivadas podrían ser administradas en aquellas mujeres que no estuvieran correctamente inmunizadas con anterioridad, mientras que las atenuadas están contraindicadas.A pesar de que la vacunación durante el embarazo es una medida preventiva muy importante, y de las recomendaciones de autoridades sanitarias, sociedades científicas y profesionales sanitarios, las coberturas vacunales son claramente mejorables, especialmente en lo que respecta a gripe y COVID-19, por lo que todo profesional sanitario que atienda a la embarazada debe ser proactivo en aconsejarlas.La Asociación Española de Pediatría (AEP), a través de su Comité Asesor de Vacunas (CAV), y la Sociedad Española de Ginecología y Obstetricia (SEGO) recomiendan las siguientes vacunaciones durante la gestación: frente a gripe y COVID-19, en cualquier trimestre del embarazo, y durante el puerperio (hasta los 6meses) en aquellas que no hubieran sido vacunadas durante la gestación; frente a tosferina con Tdpa, entre las 27 y 36 semanas de gestación (el CAV-AEP da preferencia entre las 27 y 28 semanas); y frente al VRS con RSVPreF, entre las 24 y 36 semanas de gestación, de preferencia entre las 32 y 36 semanas. (AU)


During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitisB, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated.Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines.The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines (CAV), and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36. (AU)


Subject(s)
Humans , Pregnancy , Vaccination , Whooping Cough , Influenza, Human , Severe Acute Respiratory Syndrome
6.
Clin Appl Thromb Hemost ; 30: 10760296241238211, 2024.
Article in English | MEDLINE | ID: mdl-38566607

ABSTRACT

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.


Subject(s)
Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Humans , Venous Thromboembolism/drug therapy , Prospective Studies , Anticoagulants/therapeutic use , Pulmonary Embolism/drug therapy , Risk Factors , Biomarkers , Recurrence
7.
An Pediatr (Engl Ed) ; 100(4): 268-274, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38565447

ABSTRACT

During pregnancy, physiological changes in the immune response make pregnant women more susceptible to serious infection, increasing the risk for the mother as well as the foetus, newborn and infant. All women should be correctly and fully vaccinated as they enter their reproductive years, especially against diseases such as tetanus, hepatitis B, measles, rubella and varicella. In addition to the recommended vaccines, in risk situations, inactivated vaccines could be administered to women who were not correctly vaccinated before, while attenuated vaccines are contraindicated. Despite the fact that vaccination during pregnancy is a very important preventive measure and the existing recommendations from public health authorities, scientific societies and health professionals, the vaccination coverage could clearly be improved, especially against influenza and SARS-CoV-2, so any health professional involved in the care of pregnant women should proactively recommend these vaccines. The Spanish Association of Pediatrics (AEP), through its Advisory Committee on Vaccines, and the Spanish Society of Gynaecology and Obstetrics (SEGO) recommend vaccination against the following diseases during pregnancy: against influenza and COVID-19, in any trimester of pregnancy and during the postpartum period (up to 6 months post birth) in women not vaccinated during pregnancy; against pertussis, with the Tdap vaccine, between weeks 27 and 36 of gestation (in the CAV-AEP recommendations, preferably between weeks 27 and 28); and against RSV, with RSVPreF, between weeks 24 and 36 of gestation, preferably between weeks 32 and 36.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Vaccination , Humans , Pregnancy , Female , Vaccination/standards , Pregnancy Complications, Infectious/prevention & control , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Influenza, Human/prevention & control , Influenza Vaccines/administration & dosage
8.
Life (Basel) ; 14(3)2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38541744

ABSTRACT

Lycium barbarum, known as goji berry or wolfberry, is a fruit long associated with health benefits, showing a plethora of effects ranging from antioxidant, anticancer, anti-inflammatory, and immunomodulatory effects. Its potential is attributed to the significant presence of polysaccharides, glycopeptides, polyphenols, flavonoids, carotenoids, and their derivatives. These compounds effectively counteract the action of free radicals, positively influencing cellular balance and intracellular signaling, contributing to overall cell health and function acting on multiple molecular pathways. Several fractions extracted from goji berries demonstrate antitumor properties, particularly effective against breast cancer, without showing cytotoxic effects on normal human cells. Hence, the review explored the fundamental traits of bioactive elements in Lycium barbarum and their potential in cancer treatment and, specifically, breast cancer. It focused on elucidating wolfberry's influenced biochemical pathways, its synergism with anticancer drugs, and its potential to alleviate the side effects associated with existing cancer treatments.

9.
Ugeskr Laeger ; 186(13)2024 03 25.
Article in Danish | MEDLINE | ID: mdl-38533859

ABSTRACT

Cognitive dysfunction is a well-known consequence of epilepsy in children. This review summarizes cognitive difficulties presenting in different types of childhood epilepsy. The possibility of screening and monitoring cognitive dysfunction is desirable to provide optimal support and treatment. The clinical test tool EpiTrack Junior is introduced. It was developed for screening and continuous monitoring of cognitive function in children with epilepsy.


Subject(s)
Cognitive Dysfunction , Epilepsy , Child , Humans , Anticonvulsants/therapeutic use , Neuropsychological Tests , Epilepsy/drug therapy , Cognitive Dysfunction/drug therapy , Cognition
10.
Int J Mol Sci ; 25(3)2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38338894

ABSTRACT

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.


Subject(s)
Extracellular Vesicles , MicroRNAs , Retinal Degeneration , Humans , Retina/metabolism , Retinal Degeneration/metabolism , Extracellular Vesicles/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Oxidative Stress
11.
Cureus ; 16(1): e52329, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38361685

ABSTRACT

Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.

12.
Cell ; 187(3): 659-675.e18, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38215760

ABSTRACT

The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show that NDUFA6/nuo-3(G60D) or hypoxia directly restores complex I forward activity, with downstream rescue of ETC flux and, in some cases, complex I levels. Additional screens identify residues within the ubiquinone binding pocket as being required for the rescue by NDUFA6/nuo-3(G60D) or hypoxia. This reveals oxygen-sensitive coupling between an accessory subunit and the quinone binding pocket of complex I that can restore forward activity in the same manner as hypoxia.


Subject(s)
Caenorhabditis elegans , Electron Transport Complex I , Hypoxia , Animals , Mice , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Electron Transport Complex I/metabolism , Hypoxia/genetics , Hypoxia/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Oxygen/metabolism
13.
Am J Med Genet A ; 194(5): e63530, 2024 May.
Article in English | MEDLINE | ID: mdl-38197511

ABSTRACT

MPZL2-related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty-five previously reported patients had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2-related hearing loss. A rare missense likely pathogenic variant [NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp)] located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later-onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2-related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.


Subject(s)
Cell Adhesion Molecules , Hearing Loss, Sensorineural , Humans , Cell Adhesion Molecules/genetics , Deafness/genetics , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Mutation, Missense/genetics , Pedigree , Phenotype
14.
Healthcare (Basel) ; 12(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255051

ABSTRACT

Introduction: The COVID-19 pandemic caused an international health emergency situation where nursing took on a fundamental role. The high number of patients in hospital ICUs led to a shift in nurses' working conditions and workload. Objective: The objective of this study was to describe the experiences of nurses who worked in ICUs during the acute phase of the COVID-19 pandemic. Methodology: A qualitative, descriptive study was carried out, with the participation of 21 nurses who worked in the ICU during the pandemic. Data collection took place between May and July 2021 through 21 in-depth interviews. Results: Three main themes emerged: (1) COVID-19 in ICUs: nurses on the frontline. (2) United against adversity: teamwork. (3) New optics of critical care and the nursing profession. COVID-19 was perceived with harshness, and the lack of knowledge about the virus generated confusion, anxiety and fear due to the risk of transmission to family members and relatives. The pandemic marked a shift in the management of human, material and economic resources. Novice nurses learned critical care at an accelerated pace, with significant physical and psychological strain. Expert nurses carried the burden of training new nurses. Although there were tense situations, experiencing these adverse situations as a team led to feelings of increased belonging, togetherness and professional bonding for nurses. While the participants noted an increase in motivation to continue in their profession, they also had a feeling of not having been cared for as they deserve by healthcare institutions.

15.
Children (Basel) ; 11(1)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38255423

ABSTRACT

BACKGROUND: Adolescence is a crucial time in the development of young people's identity, and sexuality is a key issue. Comprehensive sex education provides the knowledge and skills to help adolescents protect their sexual and reproductive health and rights. Policies on sex education in secondary schools are highly influential in the development of quality programmes that support comprehensive sex education. The aim of this study was to explore, describe and understand adolescents' experiences of sex education. METHODS: A qualitative study based on Gadamer's phenomenology was used. Two focus groups and four in-depth interviews were conducted with 12 private school students, followed by inductive data analysis using ATLAS.ti software 9.0. RESULTS: Two main themes were identified in the analysis: (1) sex education is a challenge for secondary schools and (2) student expectations of sex education. CONCLUSION: It is essential for adolescents to have access to comprehensive sex education that is adapted to the different stages of their development, is provided by specialised teachers, and involves their families in the process.

16.
Int J Psychol ; 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38174827

ABSTRACT

The present study examined the association of mothers' and fathers' individualism, collectivism and conformity values with parenting behaviours and child adjustment during middle childhood in an Italian sample. Children (n = 194; 95 from Naples and 99 from Rome; 49% girls) were 10.93 years old (SD = .61) at the time of data collection. Their mothers (n = 194) and fathers (n = 152) also participated. Mother and father reports were collected about parental individualism and collectivism, conformity values, warmth, family obligations expectations and their children's internalising and externalising problems. Child reports were collected about their parents' warmth, psychological control, rules/limit-setting, family obligations expectations and their own internalising and externalising behaviours. Multiple regressions predicted each of the parenting and child adjustment variables from the value variables, controlling for child gender and parent education. Results showed that maternal collectivism was associated with high psychological control, parental collectivism was associated with high expectations regarding children's family obligations and fathers' conformity values were associated with more child internalising behaviours. Overall, the present study shed light on how parents' cultural values are related to some parenting practices and children's internalising problems in Italy.

17.
Geriatr Nurs ; 55: 362-367, 2024.
Article in English | MEDLINE | ID: mdl-38171187

ABSTRACT

The objective of this research was to analyze the risk of adverse effects in patients older than 65 years with dementia and in concomitant treatment with antidementia and antipsychotic drugs and who are cared for by community nurses. A retrospective cross-sectional descriptive study was carried out. A total of 332 patients who were cared for by primary care teams participated. Most of the patients were women, totally dependent for the basic activities of daily living and residing in the family home. They were polymedicated and there was poor therapeutic adherence. The risk of adverse effects was higher in polymedicated patients who had been taking antipsychotics for longer periods and in those who had a main caregiver. However, those patients who had been assessed by the community nurse were protected from suffering adverse effects. This study demonstrates how integrated and continuous nursing care can reduce adverse effects in this type of patient.


Subject(s)
Antipsychotic Agents , Dementia , Humans , Female , Aged , Male , Antipsychotic Agents/adverse effects , Independent Living , Cross-Sectional Studies , Retrospective Studies , Activities of Daily Living
18.
Eur J Med Chem ; 266: 116128, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38232463

ABSTRACT

In this paper we present the design, synthesis, and biological evaluation of a new series of peptidomimetics acting as potent anti-SARS-CoV-2 agents. Starting from our previously described Main Protease (MPro) and Papain Like Protease (PLPro) dual inhibitor, CV11, here we disclose its high inhibitory activity against cathepsin L (CTSL) (IC50 = 19.80 ± 4.44 nM), an emerging target in SARS-CoV-2 infection machinery. An in silico design, inspired by the structure of CV11, led to the development of a library of peptidomimetics showing interesting activities against CTSL and Mpro, allowing us to trace the chemical requirements for the binding to both enzymes. The screening in Vero cells infected with 5 different SARS-CoV-2 variants of concerns, highlighted sub-micromolar activities for most of the synthesized compounds (13, 15, 16, 17 and 31) in agreement with the enzymatic inhibition assays results. The compounds showed lack of activity against several different RNA viruses except for the 229E and OC43 human coronavirus strains, also characterized by a cathepsin-L dependent release into the host cells. The most promising derivatives were also evaluated for their chemical and metabolic in-vitro stability, with derivatives 15 and 17 showing a suitable profile for further preclinical characterization.


Subject(s)
COVID-19 , Peptidomimetics , Chlorocebus aethiops , Humans , Animals , Cathepsin L , SARS-CoV-2 , Peptidomimetics/pharmacology , Protease Inhibitors/pharmacology , Vero Cells , Peptide Hydrolases , Antiviral Agents/pharmacology , Molecular Docking Simulation
19.
Nutr Metab Cardiovasc Dis ; 34(1): 177-187, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37949715

ABSTRACT

BACKGROUND AND AIMS: To investigate the efficacy and feasibility of three different 8 h time-restricted eating (TRE) schedules (i.e., early, late, and self-selected) compared to each other and to a usual-care (UC) intervention on visceral adipose tissue (VAT) and cardiometabolic health in men and women. METHODS AND RESULTS: Anticipated 208 adults (50% women) aged 30-60 years, with overweight/obesity (25 ≤ BMI<40 kg/m2) and with mild metabolic impairments will be recruited for this parallel-group, multicenter randomized controlled trial. Participants will be randomly allocated (1:1:1:1) to one of four groups for 12 weeks: UC, early TRE, late TRE or self-selected TRE. The UC group will maintain their habitual eating window and receive, as well as the TRE groups, healthy lifestyle education for weight management. The early TRE group will start eating not later than 10:00, and the late TRE group not before 13:00. The self-selected TRE group will select an 8 h eating window before the intervention and maintain it over the intervention. The primary outcome is changes in VAT, whereas secondary outcomes include body composition and cardiometabolic risk factors. CONCLUSION: This study will determine whether the timing of the eating window during TRE impacts its efficacy on VAT, body composition and cardiometabolic risk factors and provide insights about its feasibility.


Subject(s)
Cardiovascular Diseases , Intra-Abdominal Fat , Adult , Male , Humans , Female , Body Composition , Cardiometabolic Risk Factors , Educational Status , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Fasting , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
20.
Clin. appl. thromb. hemost ; 30: 1-8, 2024. ilus, tab
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1554570

ABSTRACT

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.


Subject(s)
Humans , Biomarkers , Venous Thromboembolism/drug therapy , Anticoagulants/therapeutic use , Pulmonary Embolism/drug therapy , Recurrence , Prospective Studies , Venous Thrombosis
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