Immunohistochemical evaluation of aquaporin-4 and its correlation with CD68, IBA-1, HIF-1α, GFAP, and CD15 expressions in fatal traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance

Need of orthogonal approaches in neurological disease modeling in mouse

Over the years, advancements in modeling neurological diseases have revealed innovative strategies aimed at gaining deeper insights and developing more effective treatments for these complex conditions. However, these progresses have recently been overshadowed by an increasing number of failures in clinical trials, raising doubts about the reliability and translatability of this type of disease modeling. This mini-review does not aim to provide a comprehensive overview of the current state-of-the-art in disease mouse modeling. Instead, it offers a brief excursus over some recent approaches in modeling neurological diseases to pinpoint a few intriguing strategies applied in the field that may serve as sources of inspiration for improving currently available animal models. In particular, we aim to guide the reader toward the potential success of adopting a more orthogonal approach in the study of human diseases

Hepatitis B Surface Antigen Seropositive Men in Serodiscordant Couples: Effects on the Assisted Reproductive Outcomes

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Safety and efficacy of burosumab in improving phosphate metabolism, bone health, and quality of life in adolescents with X-linked hypophosphatemic rickets

Background and objective: X-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (PHEX) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia. Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions. Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few. In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy. Methods: Five Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH)2D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities. Results: At entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH)2D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH)2D levels, and in TmP/GFR values (P < 0.05 - P < 0.0001). Serum ALP levels significantly declined (P < 0.05) to normal values. No changes of serum calcium and PTH levels (P[dbnd]NS) were found during burosumab. PROs significantly improved (P < 0.02 - P < 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH)2D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened with a significant reduction in quality of life. These consequences were not observed in the patient who continued burosumab treatment. Discussion: Our data showed that conventional treatment improved only in part the signs and symptoms of XLH. Burosumab was well tolerated and was effective in improving phosphate metabolism, bone health, and PROs. All the benefits of burosumab were lost after its discontinuation. These results suggested that continuing burosumab is required to achieve and maintain the clinical benefits of the treatment during the transition to young adulthood in patients with XLH

Characteristics of the health districts in Italy and their implication in primary health care policies: an analysis of socio‐demographic trends

The Health District (HD) is a critical component of Italy’s National Health Service, responsible for ensuring Primary Health Care (PHC) services in response to community health needs. The Italian government established a national strategic reform program, the National Recovery and Resilience Plan (PNRR), with a series of health interventions to reorganize the PHC setting (Ministerial Decree 77/2022). Our study aimed to provide a description of socio-demographic data and to assess the correlation between HDs, in order to suggest health intervention priorities in PHC reforms. We conducted a retrospective analysis using a cross-sectional record linkage of data from multiple sources to compare organizational and socio-demographic variables. A dataset was created with each of the 21 Italian Regions’ HDs data of population, land area, mean age, ageing index, old-age dependency ratio, birth rate and death rate. We then linked the HD data with the Inland Areas Project in order to categorize them from a socio-economic point of view. Our study identified comparable groups of HDs, considering demographical, socio-economic and geographical aspects. The study provides a baseline understanding of the Italian situation prior to the implementation of DM77. It also highlights that inhabitants number cannot be the only variable to take into account for the definition of Italian HDs organisation and PHC reform, providing intercorrelated variables that take into account geographic location, demographic data, and socio-economic aspects

Validation of the Italian version of the Apathy Evaluation Scale (AES-I) in institutionalized geriatric patients

Objectives: Apathy is a very common symptom in institutionalized elderly and represents a condition of both clinical and public health importance. The Apathy Evaluation Scale (AES) has been shown to be a valid and reliable tool for characterizing, quantifying and differentiating apathy in various health conditions. The aims of this study were to establish the validity and reliability of the Italian version of the AES, and to assess the severity of apathy in a sample of Italian institutionalized geriatric patients.Method: Data were collected from clinical interviews using the AES informant version (AES-I). Associations between measures of apathy and depression, cognitive functioning and perceived quality of life were evaluated, as well as the effect of the living environment on apathetic symptoms.Results: Multiple forms of reliability and validity (i.e. test-retest, internal consistency, discriminability of apathy rating from a standard measure of depression) were satisfied. Our results also show that the characteristics of the care setting may affect the severity of apathetic symptoms.Conclusions: The AES-I Italian version is a reliable and valid instrument for measuring apathy in Italian patients, also allowing a direct comparison with data gathered in other countries.

Tackling the Challenging Determination of Trace Elements in Ultrapure Silicon Carbide by LA-ICP-MS

The goal of accurately quantifying trace elements in ultrapure silicon carbide (SiC) with a purity target of 5N (99.999% purity) was addressed. The unsuitability of microwave-assisted acid digestion followed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis was proved to depend mainly on the contamination induced by memory effects of PTFE microwave vessels and by the purity levels of acids, even if highly pure ones were used in a clean environment. A new analytical protocol for the direct analysis of the solid material by laser ablation coupled with ICP-MS (LA-ICP-MS) was then exploited. Different samples were studied; the best results were obtained by embedding SiC (powders or grains) in epoxy resin. This technique has the great advantage of avoiding any source of external contamination, as grinding, pressing and sintering pretreatments are totally unnecessary. Two different laser wavelengths (266 and 193 nm) were tested, and best results were obtained with the 266 nm laser. The optimized protocol allows the determination of elements down to the sub-mg/kg level with a good accuracy level

Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs