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SommarioIl Comitato Olimpico Internazionale (CIO) consente alle atlete transgender di gareggiare nelle divisioni femminili se i loro livelli di testosterone sierico sono inferiori a 10 nmol/L dal almeno un anno. Tuttavia, questo valore è nettamente superiore rispetto alle donne cisgender. Gli elevati livelli di testosterone e i loro effetti fisiologici determinano un vantaggio nelle competizioni sportive. La terapia ormonale di affermazione di genere riduce i livelli di testosterone circolante e determina alcune variazioni nella fisiologia del testosterone nelle donne transgender con conseguente modifica delle prestazioni fisiche di queste atlete. Scopo di questa Rassegna è la valutazione dei cambiamenti indotti dalla terapia ormonale e l’analisi degli effetti irreversibili del testosterone e di come essi possano influire sulle capacità fisiche e atletiche di donne transgender, con lo scopo finale di rendere lo sport inclusivo ed equo per tutti gli atleti.

Canine parvovirus (CPV-2) modified-live virus vaccine strain can replicate in lymphoid tissues and intestinal mucosa after administration, being shed through canine faeces. Detection of vaccine strains has been reported in the bloodstream and faeces, potentially interfering with molecular diagnostic tests. The persistence of these strains in canine tissues has not yet been described. With this aim, canine tissues were tested during a molecular survey to screen for the presence of canine enteric viruses. Tissue samples from 165 dead dogs were tested by a conventional PCR assay. Positive samples and five commercial vaccines were subjected to sequence analysis. Vaccinal strains were detected and virus load was measured by using a set of real-time PCR assays using minor-groove binder (MGB) probes. Seventy-five dogs (45.4%) tested positive for CPV-2. Strains from 70 dogs were characterised as field variants. The presence of CPV sequences of vaccine origin was observed in the spleen, intestine, and mesenteric lymph nodes of five young dogs. Vaccinal strains were detected from 12 to 24 days after the last vaccine administration. Viral loads comprised between 6.3 × 10

Differential diagnosis between Parkinson’s disease (PD) and corticobasal syndrome (CBS) could be challenging at the early stage, due to the asymmetric onset of both diseases. Despite the clinical overlap, the anatomical circuits involved in these disorders are different. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) and cortical thickness (CTh) in drug-naïve PD and CBS patients for characterizing pathophysiological mechanisms underlying these conditions. Patients with a clinically probable diagnosis of PD and possible CBS were recruited. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100–150–200–300–400–500–750 ms. Asymmetry index (AI) of R2BRRC for each ISI was computed. Patients underwent a structural brain MRI and hemisphere CTh and AI of MRI was calculated. Fourteen drug-naïve PD patients and 10 patients with early CBS diagnosis were enrolled. R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100 and 150 ms (p

Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT.The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected.One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities.In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

Cigarette smoking is the main risk factor for head and neck cancer (HNC) and many HNC patients are active smokers at diagnosis. We conducted a systematic literature review and meta-analysis to quantify the survival impact of smoking cessation at or around the time of HNC diagnosis. We searched studies published until December 31, 2021, and used random-effects meta-analysis to pool study-specific estimates into summary hazard ratio (SHR) and corresponding 95% confidence intervals (CI). Sixteen studies were published between 1983 and 2021, and over 2300 HNC patients were included. Studies were diverse in terms of design, patients, tumours and treatment characteristics, and criteria used to discriminate quitters from continued smokers. HNC patients who quit smoking at or around diagnosis had significantly better overall survival than continued smokers (SHR 0.80, 95% CI 0.70-0.91, n studies = 10). A beneficial effect of post-diagnosis smoking cessation was suggested for other survival endpoints as well, but the results were based on fewer studies (n = 5) and affected by publication bias. Cessation counselling should be offered to all smokers who start a diagnostic workup for HNC and should be considered standard multidisciplinary oncological care for HNC patients. PROSPERO registration number CRD42021245560.

SommarioL’infertilità maschile, caratterizzata dall’alterazione dei parametri spermatici convenzionali e/o biofunzionali, viene riscontrata, da sola o in associazione con quella femminile, in circa il 50% dei casi di infertilità di coppia. Una causa genetica si riscontra in circa il 15% dei pazienti con azoospermia o oligozoospermia. Nonostante un approccio diagnostico approfondito, si stima però che la causa dell’infertilità rimane sconosciuta in una grande percentuale dei partner maschili delle coppie infertili. Recentemente, alcune evidenze hanno suggerito l’esistenza di nuove cause genetiche responsabili di alterazioni della spermatogenesi. Lo scopo di questa Rassegna è quello di valutare le evidenze relative alle alterazioni della spermatogenesi di natura genetica, rivedendo i dati disponibili sia nei modelli animali che nell’uomo. I dati di tale revisione della letteratura ci hanno permesso di suggerire l’uso di un pannello che comprende oltre 60 geni nell’iter diagnostico dei pazienti con alterazioni dei parametri spermatici di natura idiopatica. Alcuni di questi geni sembrerebbero associarsi a uno specifico quadro istologico testicolare. Se confermate, queste evidenze potrebbero in futuro avere un ruolo importante nell’iter decisionale relativo alla gestione del paziente infertile.

Background P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. Aim To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. Methods The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. Results Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. Conclusion This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

A new four-parameters family of constitutive functions for spherically symmetric elastic bodies is introduced which extends the two-parameters class of polytropic fluid models widely used in several applications of fluid mechanics. The four parameters in the polytropic elastic model are the polytropic exponent $\gamma$, the bulk modulus $\kappa$, the shear exponent $\beta$ and the Poisson ratio $\nu\in (-1,1/2]$. The two-parameters class of polytropic fluid models arises as a special case when $\nu=1/2$ and $\beta=\gamma$. In contrast to the standard Lagrangian approach in elasticity theory, the polytropic elastic model in this paper is formulated directly in physical space, i.e., in terms of Eulerian state variables, which is particularly useful for the applications e.g. to astrophysics where the reference state of the bodies of interest (stars, planets, etc.) is not observable. After discussing some general properties of the polytropic elastic model, the steady states and the homologous motion of Newtonian self-gravitating polytropic elastic balls are investigated. It is shown numerically that static balls exist when the parameters $\gamma,\beta$ are contained in a particular region $\mathcal{O}$ of the plane, depending on $\nu$, and proved analytically for $(\gamma,\beta)\in\mathcal{V}$, where $\mathcal{V}\subset\mathcal{O}$ is a disconnected set which also depends on the Poisson ratio $\nu$. Homologous solutions describing continuously collapsing balls are constructed numerically when $\gamma=4/3$. The radius of these solutions shrinks to zero in finite time, causing the formation of a center singularity with infinite density and pressure. Expanding self-gravitating homologous elastic balls are also constructed analytically for some special values of the shear parameter $\beta$., Comment: 40 pages, 5 figures

Introduction Temporary spacers used in the staged revision of a hip prosthetic joint infection (PJI) have been associated with several mechanical complications with very variable reported general complications rates up to 73%. The aim of this systematic review was to assess the mechanical complications associated with hip antibiotic-loaded spacers when treating periprosthetic hip PJI. Methods Through an electronic systematic search of PubMed, articles reporting mechanical complications of spacers used in the treatment of hip PJI were reviewed. Dislocations, spacer fracture, femoral fractures, and acetabular lysis rates were evaluated. Results Forty studies were included. Standardized molded spacers had a significantly higher weighted mean of total mechanical complication rates (37.2%) when compared to standardized preformed spacers (13.8%, p = 0.039), while no significant difference was found between molded spacers and manually shaped spacers. Spacer dislocation was the most frequent complication. No significant difference in mechanical complication rate was found between spacers with and without any metallic component. Conclusions Spacer placement in chronic PJI of the hip with bone and soft-tissue defects is challenging and bears a high risk of mechanical failures and progressive bone loss during the interim period. A careful patient selection for spacer implantation is mandatory.

The healthcare is often considered one of the sectors most prone to corruption, and transparency policies have been proposed in several countries to fight bribery and corruption. Indeed, the transparency of public bodies potentially plays a relevant role in preventing misbehaviour and favouring accountability. This study contributes to a broader understanding of the role of transparency in the healthcare sector using Italy as a case study. For this purpose, we first built a composite indicator to assess the differences in transparency, performance, and integrity between Italian local health authorities (LHAs) retrieving the administrative data available on their websites. Then, we used both non-parametric method and multivariate regression to explore the relationship between the performance of different expenditure functions (total production costs, administrative costs, and medical and non-medical-related service costs) at the LHA level and the transparency index. Our results show a wide difference in transparency, performance, and integrity among LHAs that does not always follow the classic north–south divide in Italy. In addition, we find results consistent with the idea that transparency is generally associated with a better capability of LHAs in the containment of healthcare expenditure while imposing larger administrative burdens. Overall, reforms promoting transparency impose administrative costs, which policymakers should bear in mind to develop less burdensome transparency measures, as they might not be a ‘free lunch’.

Demands on neural interfaces in terms of functionality, high spatial resolution, and longevity have recently increased. These requirements can be met with sophisticated silicon-based integrated circuits. Embedding miniaturized dice in flexible polymer substrates significantly improves the adaptation to the mechanical environment in the body and thus the systems’ structural biocompatibility as well as the ability to cover larger areas of the brain. This work addresses main challenges in developing a hybrid chip-in-foil neural implant. Assessments were related to: first, the mechanical compliance to the recipient tissue that allows a long-term application, and second, the suitable design that allows the implant’s scaling and modular adaptation of chip arrangement. Finite element model studies were performed to identify design rules regarding die geometry, interconnect routing, and positions for contact pads on dice. Providing edge fillets in the die base shape was an effective measure to improve die-substrate integrity and increase the area available for contact pads. Furthermore, the routing of interconnects in the immediate vicinity of die corners should be avoided, as the substrate in these areas is prone to mechanical stress concentration. Contact pads on dice should be placed with a clearance from the die rim to avoid delamination when the implant is conformed to a curvilinear body. A microfabrication process was developed to transfer, align and electrically interconnect multiple dice into conformable polyimide-based substrates. The process enabled arbitrary die shape and size and independent target positions on the conformable substrate from the die position on the fabrication wafer.

International audience; Near-surface axial tensile residual stresses (from manufacturing) are reportedly detrimental to the yield strength of cold-drawn wires. Therefore, a reliable evaluation of their magnitude is necessary. The size and geometry of electrical wires can pose challenges for experimental measurement of those residual stresses. For that reason, the finite element analysis can prove useful. However, great care must be taken with the right choice of strain hardening law for a sound assessment of residual stresses. Given the complex loading condition during cold drawing, cyclic loading arises through the wire cross section even in single-pass drawing. As a result, it is of crucial importance to account for associated backstresses. The current study makes a comparison between two different hardening laws’ prediction of axial residual stress profiles in numerically cold-drawn Cu–Al composite wires of various Al volume fractions. The impact of die geometry on this prediction was also examined for a 25%Al-wire. To that end, a combined isotropic-kinematic law and a pure isotropic constitutive equation were considered. The results imply a possible overestimation of residual stresses by the pure isotropic model at relatively low Al volume fractions. The difference between the maximum magnitudes of tensile or compressive residual stresses (predicted by the two models) could be as large as about 100 MPa (larger than the yield strength of the starting materials). Furthermore, the tooling geometry minimally affects the prediction of the hardening models. In conclusion, backstresses are not to be overlooked for accurate estimations of drawing residual stresses at low Al volume fractions.

In this paper we investigate the property of engulfing for H-convex functions defined on the Heisenberg group $${\mathbb {H}^n}$$ H n . Starting from the horizontal sections introduced by Capogna and Maldonado (Proc Am Math Soc 134:3191–3199, 2006) , we consider a new notion of section, called $${\mathbb {H}^n}$$ H n -section, as well as a new condition of engulfing associated to the $${\mathbb {H}^n}$$ H n -sections, for an H-convex function defined in $$\mathbb {H}^n.$$ H n . These sections, that arise as suitable unions of horizontal sections, are dimensionally larger; as a matter of fact, the $${\mathbb {H}^n}$$ H n -sections, with their engulfing property, will lead to the definition of a quasi-distance in $${\mathbb {H}^n}$$ H n in a way similar to Aimar et al. in the Euclidean case (J Fourier Anal Appl 4:377–381, 1998). A key role is played by the property of round H-sections for an H-convex function, and by its connection with the engulfing properties.

The association between dyslipidemia and cognitive performance in Parkinson’s disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29–9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = − 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17–0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18–0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.