Cognitive Function and Atrial Fibrillation: From the Strength of Relationship to the Dark Side of Prevention. Is There a Contribution from Sinus Rhythm Restoration and Maintenance?

Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia with an increasing prevalence over time mainly because of population aging. It is well established that the presence of AF increases the risk of stroke, heart failure, sudden death, and cardiovascular morbidity. In the last two decades several reports have shown an association between AF and cognitive function, ranging from impairment to dementia. Ischemic stroke linked to AF is a well-known risk factor and predictor of cognitive decline. In this clinical scenario, the risk of stroke might be reduced by oral anticoagulation. However, recent data suggest that AF may be a predictor of cognitive impairment and dementia also in the absence of stroke. Cerebral hypoperfusion, reduced brain volume, microbleeds, white matter hyperintensity, neuroinflammation, and genetic factors have been considered as potential mechanisms involved in the pathogenesis of AF-related cognitive dysfunction. However, a cause-effect relationship remains still controversial. Consequently, no therapeutic strategies are available to prevent AF-related cognitive decline in stroke-free patients. This review will analyze the potential mechanisms leading to cognitive dysfunction in AF patients and examine the available data on the impact of a sinus rhythm restoration and maintenance strategy in reducing the risk of cognitive decline

Hypoxic induced decrease in oxygen consumption in Cuttlefish (Sepia officinalis) is associated with minor increases in mantle octopine but no changes in markers of protein turnover

The common cuttlefish (Sepia officinalis), a dominant species in the north-east Atlantic ocean and Mediterranean Sea, is potentially subject to hypoxic conditions due to eutrophication of coastal waters and intensive aquaculture. Here we initiate studies on the biochemical response to an anticipated level of hypoxia. Cuttlefish challenged for 1 h at an oxygen level of 50% dissolved oxygen saturation showed a decrease in oxygen consumption of 37% associated with an 85% increase in ventilation rate. Octopine levels were increased to a small but significant level in mantle, whereas there was no change in gill or heart. There were no changes in mantle free glucose or glycogen levels. Similarly, the hypoxic period did not result in changes in HSP70 or polyubiquinated protein levels in mantle, gill, or heart. As such, it appears that although there was a decrease in metabolic rate there was only a minor increase in anaerobic metabolism as evidenced by octopine accumulation and no biochemical changes that are hallmarks of alterations in protein trafficking. Experiments with isolated preparations of mantle, gill, and heart revealed that pharmacological inhibition of protein synthesis could decrease oxygen consumption by 32 to 42% or Na+/K+ ATPase activity by 24 to 54% dependent upon tissue type. We propose that the decrease in whole animal oxygen consumption was potentially the result of controlled decreases in the energy demanding processes of both protein synthesis and Na+/K+ ATPase activity.info:eu-repo/semantics/publishedVersio

Percutaneous Left Atrial Appendage Occlusion: An Emerging Option in Patients with Atrial Fibrillation at High Risk of Bleeding

Atrial fibrillation (AF) is a common cardiac arrhythmia with an estimated prevalence of 1% in the general population. It is associated with an increased risk of ischemic stroke, silent cerebral ischemia, and cognitive impairment. Due to the blood flow stasis and morphology, thrombus formation occurs mainly in the left atrial appendage (LAA), particularly in the setting of nonvalvular AF (NVAF). Previous studies have shown that >90% of emboli related to NVAF originate from the LAA, thus prevention of systemic cardioembolism is indicated. According to the current guidelines, anticoagulant therapy with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), represents the standard of care in AF patients, in order to prevent ischemic stroke and peripheral embolization. Although these drugs are widely used and DOACs have shown, compared to VKAs, non-inferiority for stroke prevention with significantly fewer bleeding complications, some issues remain a matter of debate, including contraindications, side effects, and adherence. An increasing number of patients, indeed, because of high bleeding risk or after experiencing life-threatening bleedings, must take anticoagulants with extreme caution if not contraindicated. While surgical closure or exclusion of LAA has been historically used in patients with AF with contradictory results, in the recent years, a novel procedure has emerged to prevent the cardioembolic stroke in these patients: The percutaneous left atrial appendage occlusion (LAAO). Different devices have been developed in recent years, though not all of them are approved in Europe and some are still under clinical investigation. Currently available devices have shown a significant decrease in bleeding risk while maintaining efficacy in preventing thromboembolism. The procedure can be performed percutaneously through the femoral vein access, under general anesthesia. A transseptal puncture is required to access left atrium and is guided by transesophageal echocardiography (TEE). Evidence from the current literature indicates that percutaneous LAAO represents a safe alternative for those patients with contraindications for long-term oral anticoagulation. This review summarizes scientific evidences regarding LAAO for stroke prevention including clinical indications and an adequate patient selection

Presença de Dermatite Atópica em jovens e adultos com estresse psíquico: uma revisão sistemática: Presence of Atopic Dermatitis in young people and adults with psychological stress: a systematic review

O objetivo desse estudo é demonstrar a influência do estresse psíquico em pacientes jovens e adultos com dermatite atópica. A estratégia de busca para o presente artigo teve como base dados advindos do Portal da Biblioteca Virtual em Saúde - BVS: por meio de descritores “jovens e adultos, dermatite atópica, estresse psíquico” e o operador booleano “AND", aliado com os critérios de inclusão para busca, referente à textos completos nos últimos 5 anos. Dentre os 46 artigos obtidos inicialmente, apenas 12 seguiram os critérios inclusos, 5 foram excluídos baseado em seu título/resumo, resultando em 7 artigos inclusos. Dessa forma, foi de fato demonstrada uma relação de influência entre o estresse e jovens adultos com diagnóstico de dermatite atópica. Estes mostram uma tendência à somatização, como o desenvolvimento de depressão e ansiedade. O estresse também demonstrou afetar a severidade da doença, visto que contribui para o desencadeamento do ciclo vicioso de coceira, característico da dermatite atópica.                          &nbsp

Implementation of infection prevention and control components in Italian hospitals based on a nationwide survey on behalf of INSIEME project

We aim to assess the state-of-the-art of Infection Prevention and Control (IPC) practices and their results in Italian healthcare facilities 6 years after the kick-off of the new National Plan for the Control of Antibiotic Resistance (PNCAR). This was a multicenter, cross-sectional, observational study conducted between January 1st, and December 31st, 2023, among Italian hospitals. Survey questions were readapted from the WHO IPC assessment framework (IPCAF), PNCAR and INSIEME group proposals, resulting in 155 questions grouped into six sections: IPC program, surveillance, control activities for healthcare-associated infections, antimicrobial stewardship (AMS) strategies, IPC training and education, and monitoring indicators. Thirty-eight acute care Hospitals completed the survey (response rate: 30%): 26.3% of hospitals did not define an annual program and 34.2% an AMS task force. Periodic microbiology reports were available for 57.9%, hospital alcohol-based hand rubs consumption per 1000 bed-days in 42.1% and defined daily dose of antimicrobials per 100 bed-days in 55.3% hospitals with a significant difference between Northern and Southern regions (90.9% vs 22.2%; P = 0.006). Active monitoring of hand hygiene and contact isolation compliance was implemented in only half of the hospitals. Structured HAI surveillance systems were implemented in fewer than 20% of hospitals. Components on IPC implementation activity, such as no-touch sanitizing systems, checklist for environmental cleaning, informatic flags, bundles for pathogens revealed the lowest score. The appropriateness of antibiotic therapy prescribing was assessed in 73.7% of facilities. Only 42.1% of hospitals had budget goals. This survey provides a baseline assessment and identifies key barriers to the implementation of IPC programs across Italian acute care hospitals. The findings highlight priority areas for intervention and will inform the next phase of the INSIEME project, which aims to develop and implement tailored strategies that address the specific needs of healthcare workers and institutions nationwide

Formulation of a Kit for the Preparation of 111In-BzDTPA-NLS-trastuzumab Injection under Good Manufacturing Practices (GMP): An Auger Electron-emitting Radioimmunotherapeutic Agent for HER2-positive Breast Cancer

BACKGROUND: To advance 111In-BzDTPA-NLS-trastuzumab to a Phase I/II clinical trial, studies were conducted to develop a kit under GMP conditions to prepare clinical quality 111In-BzDTPA-NLS-trastuzumab injection. METHODS: Trastuzumab was buffer-exchanged into 0.1 M NaHCO3, then reacted with 10-fold molar excess of BzDTPA. The ICs were then buffer-exchanged into 0.1 M NaPO4 with 0.01% PS20. Purified BzDTPA-trastuzumab was reacted with 5-fold molar excess of sulfo-SMCC in 0.1 M NaPO4 with 0.01% PS20. Following re-purification, the ICs were reacted with 60-fold molar excess of NLS peptides. The BzDTPA-NLS-trastuzumab ICs were buffer-exchanged into 0.05 M NH4Ac with 0.01% PS20. Unit dose kits meeting specifications for pharmaceutical quality were prepared. MicroSPECT/CT was performed in mice with SK-OV-3 human ovarian cancer xenografts. RESULTS: Three kits that met specifications for pharmaceutical quality were manufactured. Tumor xenografts were imaged by microSPECT/CT. CONCLUSION: Careful selection of reaction conditions was required to obtain kits that met all specifications.M.Sc

Formulation of a Kit for the Preparation of 111In-BzDTPA-NLS-trastuzumab Injection under Good Manufacturing Practices (GMP): An Auger Electron-emitting Radioimmunotherapeutic Agent for HER2-positive Breast Cancer

BACKGROUND: To advance 111In-BzDTPA-NLS-trastuzumab to a Phase I/II clinical trial, studies were conducted to develop a kit under GMP conditions to prepare clinical quality 111In-BzDTPA-NLS-trastuzumab injection. METHODS: Trastuzumab was buffer-exchanged into 0.1 M NaHCO3, then reacted with 10-fold molar excess of BzDTPA. The ICs were then buffer-exchanged into 0.1 M NaPO4 with 0.01% PS20. Purified BzDTPA-trastuzumab was reacted with 5-fold molar excess of sulfo-SMCC in 0.1 M NaPO4 with 0.01% PS20. Following re-purification, the ICs were reacted with 60-fold molar excess of NLS peptides. The BzDTPA-NLS-trastuzumab ICs were buffer-exchanged into 0.05 M NH4Ac with 0.01% PS20. Unit dose kits meeting specifications for pharmaceutical quality were prepared. MicroSPECT/CT was performed in mice with SK-OV-3 human ovarian cancer xenografts. RESULTS: Three kits that met specifications for pharmaceutical quality were manufactured. Tumor xenografts were imaged by microSPECT/CT. CONCLUSION: Careful selection of reaction conditions was required to obtain kits that met all specifications.M.Sc

Environmental Carcinogenic Factors in Relation to Public Health

The public health problems relevant for the general population which are raised by environmental contaminations with carcinogenic factors are reviewed. The discussion includes ionizing radiations, drugs, air pollution and tobacco smoke. The recent Italian legislation on air pollution control and the Italian situation concerning prevention of cigarette smoking are commented in detail. </jats:p