Dose-Dependent Prevention of Fibrosis in Aorta of Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats by Combined Delapril and Indapamide treatment.

Combined treatment with the angiotensin-converting enzyme (ACE) inhibitor delapril and the diuretic indapamide prevented vascular damage in vital organs of salt-loaded stroke-prone spontaneously hypertensive rats (SHRsp). Whether the changes occurring after long-term hypertension could also be modulated in large arteries was investigated. Two-month-old SHRsp were salt loaded and treated with the drug regimen until they reached 50 +/- 10 mortality or around midlife. In a first experiment, delapril (12 mg/kg) and indapamide (1 mg/kg) were administered daily separately or in combination. In the second dose-finding experiment, delapril (6, 3, 1.5 mg/kg) and indapamide (0.5, 0.25, 0.125 mg/kg) in decreasing dose combinations were analyzed. Ultrastructural, histomorphometric, and biochemical studies were performed on the thoracic aorta. When compared with delapril (12 mg/kg) or indapamide (1 mg/kg) administered individually for 5 months, the combination 12 + 1 mg/kg was able to prevent the increase in extracellular matrix deposition observed in other treatment groups, as assessed by histomorphometry or 4-OH-proline biochemical determination. In the second experiment, a half-dose (delapril 6 mg/kg + indapamide 0.5 mg/kg) combination was similarly effective in counteracting fibrosis, but the other doses progressively failed. In the first experiment, the combination had a stabilizing effect on hypertension and stimulated diuresis. In the second experiment, arterial blood pressure values and sodium balance were not consistently affected by the treatments that antagonized fibrosis (i.e., delapril 6 mg/kg + indapamide 0.5 mg/kg and, less efficiently, delapril 3 mg/kg + indapamide 0.25 mg/kg). These results suggest that indapamide interacts with ACE inhibitors to limit aortic fibrosis independent of any well-established mechanism

Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB

The serpinopathies are human pathologies caused by mutations that promote polymerisation and intracellular deposition of proteins of the serpin superfamily, leading to a poorly understood cell toxicity. The dementia FENIB is caused by polymerisation of the neuronal serpin neuroserpin (NS) within the endoplasmic reticulum (ER) of neurons. With the aim of understanding the toxicity due to intracellular accumulation of neuroserpin polymers, we have generated transgenic neural progenitor cell (NPC) cultures from mouse foetal cerebral cortex, stably expressing the control protein GFP (green fluorescent protein), or human wild type, G392E or delta NS. We have characterised these cell lines in the proliferative state and after differentiation to neurons. Our results show that G392E NS formed polymers that were mostly retained within the ER, while wild type NS was correctly secreted as a monomeric protein into the culture medium. Delta NS was absent at steady state due to its rapid degradation, but it was easily detected upon proteasomal block. Looking at their intracellular distribution, wild type NS was found in partial co-localisation with ER and Golgi markers, while G392E NS was localised within the ER only. Furthermore, polymers of NS were detected by ELISA and immunofluorescence in neurons expressing the mutant but not the wild type protein. We used control GFP and G392E NPCs differentiated to neurons to investigate which cellular pathways were modulated by intracellular polymers by performing RNA sequencing. We identified 747 genes with a significant upregulation (623) or downregulation (124) in G392E NS-expressing cells, and we focused our attention on several genes involved in the defence against oxidative stress that were up-regulated in cells expressing G392E NS (Aldh1b1, Apoe, Gpx1, Gstm1, Prdx6, Scara3, Sod2). Inhibition of intracellular anti-oxidants by specific pharmacological reagents uncovered the damaging effects of NS polymers. Our results support a role for oxidative stress in the cellular toxicity underlying the neurodegenerative dementia FENIB

Improvements of Decision Support Systems for Public Administrations via a Mechanism of Co-creation of Value

This paper focuses on a possible improvement of knowledge-based decision support systems for human resource management within Public Administrations, using a co-creation of value's mechanism, according to the Service-Dominant Logic (SDL) paradigm. In particular, it applies ontology-driven data entry procedures to trigger the cooperation between the Public Administration itself and its employees. Advantages in such sense are evident: constraining the data entry process by means of the term definition ontology improves the quality of gathered data, thus reducing potential mismatching problems and allowing a suitable skill gap analysis among real and ideal workers competence profiles. The procedure foresees the following steps: analyzing organograms and job descriptions; modelling Knowledge, Skills and Attitudes (KSA) for job descriptions; transforming KSAs of job descriptions into a standard-based model with integrations of other characteristics; extracting information from Curricula Vitae according to the selected model; comparing profiles and roles played by the employees. The 'a priori' ontology-driven approach adequately supports the operations that involve both the Public Administration and employees, as for the data storage of job descriptions and curricula vitae. The comparison step is useful to understand if employees perform roles that are coherent with their own professional profiles. The proposed approach has been experimented on a small test case and the results show that its objective evaluation represents an improvement for a decision support system for the re-organization of Italian Public Administrations where, unfortunately often, people are engaged in activities that are not so close to their competences

Two cycles of Atosiban in preventing preterm birth in twin pregnancies

Twin gestation contributes significantly to perinatal morbidity and mortality related to high occurrence of preterm birth. We evaluated 202 women consecutively selected with twin pregnancies and threatened preterm labor. 98 women were threatened with a single cycle of Atosiban; 34% of them delivered before 34 weeks. The study group consisted of 104 patients submitted to a second cycle of Atosiban because of regular uterine contractions and or cervical length modifications occurred from 48 hours to 7 days and gestational age was prior to 32 week of gestation (group A). After the second cycle of Atosiban, 49 out of 104 patients received a treatment with a vaginal tablet of lactoferrin (group B). After the second cycle of Atosiban, 84% of patients of group A and 90% of patients of group B delivered after 34 weeks. The overall rate of delivery before 34 weeks in the studies groups was of 16%. In our experience, repeated cycles of Atosiban have shown effectiveness in delaying delivery in twin pregnancies. It seems logical to use an oxytocin receptor antagonist as first line drugs in twin pregnancies because of the increased risk of pulmonary edema

Novel pathogenic mechanisms of congenital insensitivity to pain with anhidrosis genetic disorder unveiled by functional analysis of neurotrophic tyrosine receptor kinase type 1/nerve growth factor receptor mutations.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disease characterized by absence of reaction to noxious stimuli and anhidrosis. The genetic bases of CIPA have remained long unknown. A few years ago, point mutations affecting both coding and noncoding regions of the neurotrophic tyrosine receptor kinase type 1 (NTRK1)/nerve growth factor receptor gene have been detected in CIPA patients, demonstrating the implication of the nerve growth factor/NTRK1 pathway in the pathogenesis of the disease. We have previously shown that two CIPA mutations, the G571R and the R774P, inactivate the NTRK1 receptor by interfering with the autophosphorylation process. We have extended our functional analysis to seven additional NTRK1 mutations associated with CIPA recently reported by others. Through a combination of biochemical and biological assays, we have identified polymorphisms and pathogenic mutations. In addition to the identification of residues important for NTRK1 activity, our analysis suggests the existence of two novel pathogenic mechanisms in CIPA: one based on the NTRK1 receptor processing and the other acting through the reduction of the receptor activity

Incidencia de la salud mental en la productividad laboral

Diversos estudios realizados actualmente en el mundo demuestran la relación existente entre los trastornos mentales no tratados con el ausentismo laboral, la baja productividad, el aumento de accidentes, los conflictos laborales y la mala relación con los compañeros de trabajo y con los jefes. Es por ello por lo que el propósito de esta investigación es analizar la incidencia de la salud mental en la productividad laboral. Para cumplir con este propósito, se asumió la metodología de un artículo de revisión, investigación documental de tipo monográfica. Obteniendo como resultado, que la salud mental es un componente básico de productividad personal y laboral. Trabajadores sanos son más productivos. La productividad y la calidad laboral van más allá de cumplir un horario, implica la intención y el propósito de lo que se hace, interviniendo directamente la motivación y el deseo. Al tener salud mental, existe un equilibrio entre lo que se espera, lo que se desea y lo que se tiene, aumentando la productividad no solo laboral sino en todos los ámbitos de la vida

Extracapsular femoral neck fractures treated with total hip arthroplasty: identification of a population with better outcomes

BACKGROUND: Femoral neck fractures (FNF) are associated to patient’s disability, reduced quality of life and mortality. None of the fixation devices commonly used for extracapsular (EC) FNF (i.e., dynamic hip screws (DHS) and intramedullary nails (IN)) is clearly superior to the other, especially in case of unstable fractures (31.A2 and 31.A3 according to AO/OTA classification). The aim of our study was to identify a sub-population of patients with EC fractures in which better outcomes could be obtainable using total hip arthroplasty (THA). METHODS: All patients with EC unstable fractures treated with THA were included in the present study. Demographic data, American Society of Anesthesiologists (ASA) score, hospitalization length, transfusion rate, implant-related complications and mortality rate were collected. Clinical outcomes were evaluated using the Oxford Hip Score (OHS), while patients’ general health status through the 12 Item Short Form questionnaires (SF-12). RESULTS: 30 patients (7 male; 23 female) with a mean age of 78.8 years were included. The 1-year mortality rate was 13.3%. The mean OHS was 27.5, while the mean SF-12 were 45.84 for the mental item and 41.6 for the physical one. Age was the only factor associated with the OHS and patients older than 75 years presented a 12- fold higher risk of developing bad outcomes. CONCLUSIONS: THA seems to be a viable option for unstable EC fractures, with good clinical outcomes, especially in patients younger than 75 years of age. The mortality rate associated with THA in EC fractures is low and anyway comparable with IN

Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs