The association between hypoparathyroidism and cognitive impairment: a systematic review.

CONTEXT AND PURPOSE: Hypocalcemia and low parathyroid hormone levels have been commonly suggested as factors able to induce central nervous system disturbances. However, evidences on the occurrence of cognitive impairment are limited or underestimated. The aim of this review is, therefore, to systematically summarize the available evidence concerning the occurrence of cognitive impairment among subjects suffering from idiopathic or secondary hypoparathyroidism. METHODS: A systematic selection of the available literature was performed by searching the online databases PubMed, Scopus and Web of Knowledge. RESULTS: The present systematic review included sixteen case report articles and one cross-sectional controlled study. Case reports were the most representative literature sources and involved ten women and seven men. The presence of cognitive impairment was mostly discussed in association with idiopathic hypoparathyroidism (HPT); five articles described the occurrence of cognitive impairment following postsurgical HPT. The case-controlled study reported a significant presence of peculiar cognitive deficits (e.g. reduced inhibitory control, impairment in visuo-spatial functioning among, and psychomotor retardation) among HPT subjects compared to healthy controls, with serum total calcium and its product with phosphorus as independent predictors of neuropsychological dysfunctions. CONCLUSION: Even though mostly based on single case reports, the presence of neuropsychological dysfunctions in the context of HPT appears to be a consistent core finding.

Carbapenem Consumption and Rate of carbapenemresistant gram-negative bacteria: results from the Sicilian Surveillance System.

Conclusion: The results of the present study highlight the need for comprehensive strategies targeting the appropriate use of antibiotics and infection control measures. Background: In the last decades, multidrug-resistant gram-negative bacteria have been increasing and they are involved in severe healthcare associated infections. In treating drug-resistant gram-negative bacterial infections, carbapenems are generally administered as a last choice. However, the rate of carbapenemresistant bacteria is constantly increasing the last years. The aim of the present study is to describe the relationship between the rate of carbapenem-resistant gram-negative bacteria and antibiotic consumption intensity. Study design: In 2017, the Sicilian Region implemented a regional surveillance system to describe and analyze consumption of antibiotics in hospital settings, as well as prevalence of antibiotic resistant microorganisms. Methods: Resistance data were retrospectively collected from routinary clinical antimicrobial susceptibility tests. Resistance rates (RRs) of carbapenems were calculated and Spearman's correlation analysis was performed to investigate the relationship between annual antibiotic consumption and rate of carbapenem resistance. Results: In 2015, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 43.9 %, and was positively correlated with beta-lactam consumption (R=0.529, p<0.01), and with carbapenem consumption (R=0.364, p<0.05). In 2016, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 53.8 %, and was positively correlated with carbapenem antibiotic consumption (R=0.364, p<0.05). In 2017, the overall prevalence of carbapenem-resistant Klebsiella pneumoniae isolates was 58.7 %, and was significantly positively correlated with carbapenem antibiotic consumption (R=0.427, p<0.05). In 2015, the overall prevalence of carbapenem-resistant Escherichia coli isolates was 6.5 %, and was significantly positively correlated with antibiotic consumption for the ATC class J01 (i.e., antibacterial for systemic use) (R=0.402, p<0.05).

Declines in Pediatric Bacterial Meningitis in the Republic of Benin Following Introduction of Pneumococcal Conjugate Vaccine: Epidemiological and Etiological Findings, 2011-2016.

BACKGROUND: Pediatric bacterial meningitis (PBM) remains an important cause of disease in children in Africa. We describe findings from sentinel site bacterial meningitis surveillance in children <5 years of age in the Republic of Benin, 2011-2016. METHODS: Cerebrospinal fluid (CSF) was collected from children admitted to Parakou, Natitingou, and Tanguieta sentinel hospitals with suspected meningitis. Identification of Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Neisseria meningitidis (meningococcus) was performed by rapid diagnostic tests, microbiological culture, and/or polymerase chain reaction; where possible, serotyping/grouping was performed. RESULTS: A total of 10 919 suspected cases of meningitis were admitted to the sentinel hospitals. Most patients were 0-11 months old (4863 [44.5%]) and there were 542 (5.0%) in-hospital deaths. Overall, 4168 CSF samples were screened for pathogens and a total of 194 (4.7%) PBM cases were confirmed, predominantly caused by pneumococcus (98 [50.5%]). Following pneumococcal conjugate vaccine (PCV) introduction in 2011, annual suspected meningitis cases and deaths (case fatality rate) progressively declined from 2534 to 1359 and from 164 (6.5%) to 14 (1.0%) in 2012 and 2016, respectively (P < .001). Additionally, there was a gradual decline in the proportion of meningitis cases caused by pneumococcus, from 77.3% (17/22) in 2011 to 32.4% (11/34) in 2016 (odds ratio, 7.11 [95% confidence interval, 2.08-24.30]). Haemophilus influenzae meningitis fluctuated over the surveillance period and was the predominant pathogen (16/34 [47.1%]) by 2016. CONCLUSIONS: The observed decrease in pneumococcal meningitis after PCV introduction may be indicative of changing patterns of PBM etiology in Benin. Maintaining vigilant and effective surveillance is critical for understanding these changes and their wider public health implications.

Appropriateness of perioperative antibiotic prophylaxis in two Italian hospitals: a pilot study.

BACKGROUND: Appropriate perioperative antibiotic prophylaxis has been shown to be an effective measure for preventing surgical site infections and to avoid complications including increased antimicrobial resistance. The objective of the present study was to evaluate the appropriateness of perioperative antibiotic prophylaxis in two Italian hospitals. STUDY DESIGN: In 2016 a survey was prospectively carried out at two hospitals (identified as A and B) and all patients who underwent a surgical operation were enrolled. METHODS: For each patient, perioperative antibiotic prophylaxis data were collected and appropriateness of perioperative antibiotic prophylaxis was assessed according to the national guidelines (SNLG-17, 2011). RESULTS: During the study period, 107 and 467 operations were included. Compliance to perioperative antibiotic prophylaxis according to indication was 72.3% (hospital A) and 77.9% (hospital B). Perioperative antibiotic prophylaxis was administered <60 min before the skin incision in 89.1% of surgical procedures in hospital A and in 78.4% in hospital B. In hospital A, the recommended molecule of antibiotic was correctly administered in 87.8% of surgeries (n= 36), while, in hospital B, the antibiotic was correctly administered only in 9.8% of surgeries. Antibiotic prophylaxis was not extended postoperatively or did not exceed 24 hours after the end of the surgery in 99% and 8.9% of the procedures in hospital A and B, respectively. CONCLUSION: Our study found an overall low compliance to perioperative antibiotic prophylaxis mainly regarding antibiotic choice and total duration of prophylaxis. The Italian Study Group of Hospital Hygiene - Italian Society of Hygiene, Preventive Medicine and Public Health, together with the National Association of Hospital Physician, promoted the implementation of the project "Choosing wisely - Hospital Hygiene", and, among the list of the 5 procedures with the highest evidence of inappropriateness, the timing and the duration of administration of perioperative antibiotic prophylaxis have been included and a multicenter study has been launched to evaluate the appropriateness of perioperative antibiotic prophylaxis components in all the participating Italian hospitals.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

PURPOSE: Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. METHODS: 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). RESULTS: In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). CONCLUSIONS: Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate.

OBJECTIVE: Vitamin D deficiency is widespread and often reported in subjects treated for osteoporosis. Optimal vitamin D repletion was previously shown to maximize the efficacy of anti-resorptive agents. To date, no information exists about the role of vitamin D in the response to strontium ranelate (SrR) treatment. The aim of our study was to investigate the BMD response to SrR in accordance with change of vitamin D status. METHODS: A retrospective analysis of 108 women receiving SrR for postmenopausal osteoporosis was carried out. Women were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were measured at baseline after 18-months. All participants were divided into two groups according to the median variation of 25(OH)D over the observation period. RESULTS: SrR was associated with improvement of BMD at lumbar spine (p < 0.0001) and to a non significant variation at femoral neck (p = 0.2). Only subjects with Δ25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p = 0.03). Change of BMD at femoral neck was positively associated with modification of ALP (r = 0.28, p = 0.01). This association was not maintained when considering only women with Δ25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple regression analysis, ALP change was the only predictor of femoral neck BMD modification (ß 0.13; SE 0.05; p = 0.01). CONCLUSION: Improvement of vitamin D status was associated with enhancement of BMD response to SrR in women with postmenopausal osteoporosis, in particular, at femoral neck.

Parkinsonism and severe hypothyroidism in an elderly patient: a case of lithium toxicity due to pharmacological interactions.

WHAT IS KNOWN AND OBJECTIVE: Hypothyroidism is a common clinical side effect of lithium treatment, whereas parkinsonism is a very rare adverse event. A number of case series of clinical signs of reversible and permanent parkinsonism due to lithium toxicity have been previously published, but never in association with hypothyroidism. We describe a rare clinical case of concurrent reversible parkinsonism and severe hypothyroidism due to lithium toxicity. CASE SUMMARY: The patient was a 74-year-old woman chronically treated with carbonate lithium (300 mg, twice daily) and clomipramine (75 mg, once daily); she also received valsartan (160 mg) plus hydrochlorothiazide (12·5 mg), once daily. The patient was visited after a 1-week history of progressively worsening and disabling parkinsonism. Laboratory tests showed elevated values of lithium and thyroid stimulating hormone (TSH) serum concentrations as well as reduced circulating thyroid hormone serum concentrations. Lithium treatment was discontinued; treatment with levothyroxine and saline solution i.v. was readily performed, and valsartan plus hydrochlorothiazide were replaced with amlodipine (5 mg, once daily). Within a few days, the patient showed a rapid improvement in overall clinical condition, but complete resolution of neurologic symptoms occurred only after about 5 months. WHAT IS NEW AND CONCLUSION: Lithium toxicity may present with concurrent hypothyroidism and parkinsonism. In the present case, interaction with valsartan and hydrochlorothiazide most likely played an important role. In patients who receive chronic therapy with lithium, prescribers should monitor lithium serum concentration both periodically and immediately at the onset of signs and symptoms, potentially related to lithium toxicity.

Access to medically-assisted procreation: the withdrawal of paternal consent in the maze of law n. 40/2004.

Abstract: The law (No.40/2004) stipulates that consent to Medically Assisted Procreation (MAP) remains irrevocable post ovum fertilization. Cryo-preservation introduces complexities, enabling embryo implantation requests after a couple's separation and the dissolution of the original parenthood plan. Constitutional Court Ruling No.161 in 2023 affirmed that the prohibition of revoking consent to MAP aligns with the Italian Constitution and the jurisprudence of the European Court of Human Rights. This delicate equilibrium of conflicting interests upholds human freedom, allowing consent revocation prior to ovocyte fertilization. Permitting revocation until implantation could inflict more significant harm: the infertile woman can in fact miss the opportunity to become a mother, impacting her psychophysical well-being and freedom of self-determination. Moreover, the embryo loses the chance to live, remaining in cryopreservation, which violates its dignity. Addressing this issue requires thorough communication by medical profession-als to inform couples about the limitations on consent revocation. An element of objectivity in terms of standards and evidence-based guidelines, from which norms must originate, is of utmost importance. Relying on broadly shared rules, especially at the international level, is vital in light of the unremitting scientific advances in MAP, as in other areas of medicine, which will open up new opportunities for which current legal/regulatory frameworks are inadequate.

Is there such a thing as an indispensable skills profile to be a good doctor? "Life skills" as essential capabilities in the medicoforensic professions.

Abstract: This writing aims to convey the essential nature and features of a cultural tool based on a set of skills and capabilities generally referred to as "life skills", which allow for the proper management (in the medical and medical-forensic professional realms) of daily situations in an effective and rewarding fashion. Such a process is based on individual tools such as communication, problem solving, stress management, self-control, the ability to make timely decisions, empathy, creativity and the opportunity to work in a multidisciplinary setting. Life skills include everything the professional should rely on in order to minimize the risks of a professional error, through the acquisition of knowledge and behavioral traits which constitute the fundamental, experience-based starting point. The chief objective of this commentary is to outline the scope of a straightforward discussion by specifically defining such skills; that in turn will make it possible to identify all the technical issues to address during the medical-diagnostic assessment, also from a medico-legal perspective, in order to frame the residual life skills and evaluate the possibilities of recovery and any disabilities, based on observation and interactions with each patient aimed at weighing their psychophysical performance.

Consequences of COVID-19 restrictions on adolescent mental health and drug abuse dynamics.

The COVID-19 pandemic has hit elderly people the hardest in terms of severity and mortality. However, it is also evident that children and adolescents have been significantly impacted and experienced major disruptions in their lives. The psychological, mental, and developmental repercussions have been major and have led to a reshaping of drug abuse dynamics and substance addiction. The authors have outlined a narrative review of the major issues affecting adolescents and their mental well-being by clarifying the lingering effects and pandemic aftermath, especially on drug abuse, developmental aspects, and behavioral addiction. The unique traits of adolescent risk factors have been outlined, in order to identify areas to be prioritized for future strategies. Possible repercussions on juvenile crime linked to social estrangedness and disrupted interactions have been briefly explored as well. All such aspects are highly meaningful and relevant from a medicolegal perspective as well. The looming mental health crisis involving youngsters will have to be confronted by fine-tuning and optimizing mental health care services, building on current experiences, raising awareness, and eliminating the stigma that often comes with mental issues. Healthcare systems should look at the current scenario as an opportunity to improve care delivery to eliminate access inequalities and stigmatization of mental issues and raise awareness for the benefit and well-being of all. Similarly, law enforcement, lawmakers, and the judiciary will have to account for such factors, too, as will economic policy-makers. In that regard, a set of defining criteria has been framed in order to provide a degree of objectivity when meeting the unique challenges of the pandemic for youth mental health, in a comprehensive and tailored fashion.

Does obesity really affect renal transplantation outcomes?

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with stage 5 chronic kidney disease (CKD). About 60% of CKD patients are overweight or obese at the time of kidney transplantation, and post-transplant obesity occurs in 50% of patients, with a weight gain of 10% in the first year and high risk of cardiovascular mortality. Obesity is associated with an increased risk of delayed graft function (DGF), acute rejection, surgical complications, graft loss and mortality. The aim of this study is to assess the clinical evolution of obese and overweight patients that have received a kidney transplant, based on short- and long-term complications associated with a higher BMI. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study was conducted with 104 kidney or pancreas-kidney transplant patients between March 2017 and December 2020, with a follow-up until April 2021. For comparative analysis, patients were grouped according to BMI. RESULTS: Mean age was of 56.65 years, 60.6% male and 39.4 % female. Overweight patients experienced prolonged surgeries, more surgical wound dehiscence, delayed graft function, hernias, proteinuria and more indications for renal biopsies. Additionally, obese patients displayed more DGF, indications for renal biopsies, proteinuria, development of diabetes mellitus, atrial fibrillation and needed prolonged hospital stays. CONCLUSIONS: Despite a high prevalence of comorbidity in the overweight and/or obese population, we found no reduction in patient and/or graft survival. However, longer follow-up is needed.

Radial head prosthesis disassembly: case report and medico-legal implications.

BACKGROUND: The aim of the treatment of radial head comminuted fractures is the restoration of anatomical normalcy to avoid the risk of several complications such as joint instability. Among the options for the treatment of such fractures, it is worth mentioning osteosynthesis, resection of the radial head or prosthetic replacement. In the presence of comminution or severe dislocation of the fracture's fragments, as in our patient's type III Mason fracture, prosthesis implantation is the treatment of choice. CASE REPORT: This clinical case reports a 22-year-old volleyball player, who during training suffered a comminuted fracture of the radial head, type III according to Mason's classification. A prosthesis was implanted. The post-operative course took place regularly. However, approximately three months after surgery, the patient experienced sudden pain and functional limitation following a normal elbow extension movement, so much so that he required medical attention in our emergency room. Following all the appropriate clinical-instrumental tests, a complete dissociation of the bipolar prosthesis of the radial head was found. CONCLUSIONS: Our clinical case shows the disassembly of a bipolar radial head prosthesis, a rather rare complication. From a medicolegal perspective, the patients should be aware of the increased risk of requiring further surgery after radial head replacement. When patients are thoroughly informed, they can cooperate and comply with indications more effectively, thus taking an active role in recovery management.

Kidney stones in renal transplant recipients: A systematic review.

INTRODUCTION: Lithiasis in renal graft recipients might be a dangerous condition with a potential risk of organ function impairment. EVIDENCE ACQUISITION: A systematic literature search was conducted through February 2023. The primary objective was to assess the incidence of lithiasis in kidney transplant (KT) recipients. The secondary objective was to assess the timing of stone formation, localization and composition of stones, possible treatment options, and the incidence of graft loss. EVIDENCE SYNTHESIS: A total of 41 non-randomized studies comprising 699 patients met our inclusion criteria. The age at lithiasis diagnosis ranged between 29-53 years. Incidence of urolithiasis ranged from 0.1-6.3%, usually diagnosed after 12 months from KT. Most of the stones were diagnosed in the calyces or in the pelvis. Calcium oxalate composition was the most frequent. Different treatment strategies were considered, namely active surveillance, ureteroscopy, percutaneous/combined approach, or open surgery. 15.73% of patients were submitted to extracorporeal shock wave lithotripsy (ESWL), while 26.75% underwent endoscopic lithotripsy or stone extraction. 18.03% of patients underwent percutaneous nephrolithotomy whilst 3.14% to a combined approach. Surgical lithotomy was performed in 5.01% of the cases. Global stone-free rate was around 80%. CONCLUSIONS: Lithiasis in kidney transplant is a rare condition usually diagnosed after one year after surgery and mostly located in the calyces and renal pelvis, more frequently of calcium oxalate composition. Each of the active treatments is associated with good results in terms of stone-free rate, thus the surgical technique should be chosen according to the patient's characteristics and surgeon preferences.

Cumulative morbidity of ureteroscopy for upper tract urothelial carcinoma.

OBJECTIVE: To assess complications after ureteroscopy (URS) for upper tract urothelial carcinoma (UTUC) management and to assess its postoperative cumulative morbidity burden using the Comprehensive Complication Index (CCI). MATERIALS AND METHODS: Single center retrospective study including patients submitted to URS for UTUC suspicion. URSs were both diagnostic and operative. Postoperative complications were recorded according to the EAU Guidelines and graded according to Clavien-Dindo Classification (CDC). The cumulative postoperative morbidity burden developed by patients experiencing multiple events was assessed using the CCI. Multivariable logistic regression (MLR) analyses identified factors independently associated with the development of any grade and major postoperative complications. RESULTS: Overall, 360 patients with UTUC suspicion were included with a total of 575 URSs performed. The cumulative number of all postoperative complications recorded was 111. In 86 (15%) procedures, patients experienced at least one postoperative complication, while 25 (4.3%) experienced more than one complication. Of these, 16 (14%) were severe (CDC ≥ IIIa). The most frequent type of complications were urinary (34%), bleeding (30%) and infectious (30%). The higher the CDC grade, the higher the median CCI, with a statistically significant increase in median CCI from CDC II to major complications. Patients who experienced intraoperative complications were at higher risk of developing any grade and major postoperative complications at MLR. CONCLUSIONS: Complications after ureteroscopy for UTUC are relatively uncommon events. Patients who experience intraoperative complications are at higher risk of developing postoperative complications. The comprehensive complication index appeared more representative of the cumulative postoperative morbidity rather than the Clavien-Dindo classification.

Compressive stress triggers fibroblasts spreading over cancer cells to generate carcinoma in situ organization.

At the early stage of tumor progression, fibroblasts are located at the outer edges of the tumor, forming an encasing layer around it. In this work, we have developed a 3D in vitro model where fibroblasts' layout resembles the structure seen in carcinoma in situ. We use a microfluidic encapsulation technology to co-culture fibroblasts and cancer cells within hollow, permeable, and elastic alginate shells. We find that in the absence of spatial constraint, fibroblasts and cancer cells do not mix but segregate into distinct aggregates composed of individual cell types. However, upon confinement, fibroblasts enwrap cancer cell spheroid. Using a combination of biophysical methods and live imaging, we find that buildup of compressive stress is required to induce fibroblasts spreading over the aggregates of tumor cells. We propose that compressive stress generated by the tumor growth might be a mechanism that prompts fibroblasts to form a capsule around the tumor.

Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene.

Griscelli disease (OMIM 214450) is a rare autosomal recessive disorder characterized by pigmentary dilution, variable cellular immunodeficiency and onset of acute phases of uncontrolled lymphocyte and macrophage activation, leading to death in the absence of bone-marrow transplantation. The pigmentary dilution is characterized by a diffuse skin pigmentation, silvery hair, large clumps of pigments in the hair shafts (Fig. 1) and an accumulation of melanosomes in melanocytes, with abnormal transfer of the melanin granules to the keratinocytes. Immunological abnormalities are characterized by absent delayed-type cutaneous hypersensitivity and an impaired natural-killer cell function. A similar disorder has been described in the dilute lethal mouse--which, however, differs by the occurrence of a severe neurological disorder. The dilute locus encodes myosin-Va, a member of the unconventional myosin family. Myosins bind actin and produce mechanical force through ATP hydrolysis. Some members of this family are thought to participate in organelle-transport machinery. Because of the phenotype resulting in the dilute mouse and because of their potential role in intracellular transport, unconventional myosin-encoding genes were regarded as candidate genes for Griscelli disease. Here we report that the Griscelli disease locus co-localizes on chromosome 15q21 with the myosin-Va gene, MYO5a, and that mutations of this gene occur in two patients with the disease. Griscelli disease is therefore a human equivalent of dilute expression in the mouse.

Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome.

Griscelli syndrome (GS, MIM 214450), a rare, autosomal recessive disorder, results in pigmentary dilution of the skin and the hair, the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes. Most patients also develop an uncontrolled T-lymphocyte and macrophage activation syndrome (known as haemophagocytic syndrome, HS), leading to death in the absence of bone-marrow transplantation. In contrast, early in life some GS patients show a severe neurological impairment without apparent immune abnormalities. We previously mapped the GS locus to chromosome 15q21 and found a mutation in a gene (MYO5A) encoding a molecular motor in two patients. Further linkage analysis suggested a second gene associated with GS was in the same chromosomal region. Homozygosity mapping in additional families narrowed the candidate region to a 3.1-cM interval between D15S1003 and D15S962. We detected mutations in RAB27A, which lies within this interval, in 16 patients with GS. Unlike MYO5A, the GTP-binding protein RAB27A appears to be involved in the control of the immune system, as all patients with RAB27A mutations, but none with the MYO5A mutation, developed HS. In addition, RAB27A-deficient T cells exhibited reduced cytotoxicity and cytolytic granule exocytosis, whereas MYO5A-defective T cells did not. RAB27A appears to be a key effector of cytotoxic granule exocytosis, a pathway essential for immune homeostasis.

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Beneficial effects of music in the healing process of traumatic injuries: perceptual control of suffering and possible abatement of disability conditions.

Abstract: Numerous scientific studies report that listening to music can beneficially affect physical and mental health, and even expedite the healing process of traumatic conditions. One of the most noteworthy positive effects of music lies in its ability to control stress and anxiety by lowering heart rate, blood pressure and blood cortisol levels. Furthermore, music can help improve mood especially in traumatized people who are faced with a wide range of negative emotions, reducing symptoms of depression and stimulating the production of dopamine in the brain, favorably inducing sleep quality, thanks to the their relaxing action. Listening to music can stimulate brain activity and improve short-term memory and concentration, having positive effects on the healing process of traumatic pathologies. Therefore, music should be considered a complementary treatment option for people facing treatment for traumatic pathologies, also stimulating the production of endorphins in the brain and intervening on pain control, resulting in positive effects on the quality of life of the traumatized. Furthermore, music can help people express their emotions and communicate with others, providing a way to connect with the world and share similar experiences, reducing social isolation and improving emotional well-being.

The core notion of euthanasia in its primordial beginnings.

Abstract: This article provides a brief review of the history of euthanasia, which has always been an ethical, social, legal and medical issue. Euthanasia, meaning "good death" refers to the practice of ending a life to relieve pain and distress. The term was already known in ancient Greece, from the time of Plato, who advocated the suppression of those who were not healthy "of body and soul". Completely different was the thinking of Hippocrates, who mentioned it in his oath, laying the foundation for modern medical ethics based on absolute respect for the person and human life. Recognizing the growing interest in the topic, this writing succinctly outlines the historical evolution of the concept of euthanasia limited to its origins.