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A 40-year-old Down patient without previous cardiological history was admitted to our institution for dyspnoea after COVID-19 vaccine. CT scan revealed a pulmonary thromboembolism. One week later, he developed neurological impairment and CT scan evidenced a left parietal ischaemic lesion. Concomitantly, he underwent echocardiography showing an atrioventricular septal defect typically associated to Down syndrome and never diagnosed earlier. The diagnosis of paradoxical embolisation was then supposed. Echocardiography also revealed a severe right heart section dilatation, with bidirectional shunt on the septal defects and systemic right heart pressure. Down patients affected by CHD are more prone to develop pulmonary vasculopathy than non-syndromic patients. In this case, the pulmonary vasculopathy was further exacerbated by the pulmonary embolism and by the late diagnosis of CHD. Finally, an appropriate timely diagnosis of atrioventricular septal defect could potentially avoid the neurological complication in this patient.

The Hamamatsu R14374-02 3-inch photomultiplier tube is an improved version of the previous R12199-02 model. It will be used for the completion of the KM3NeT neutrino telescope. Five hundred photomultipliers have been characterized for dark count rate, timing spread, and spurious pulses. The quantum efficiency, the gain and the peak-to-valley ratio have also been measured for a sub-sample of two hundred PMTs in order to determine parameter values needed as input to numerical simulations of the detector.

The Hamamatsu R14374-02 3-inch photomultiplier tube is an improved version of the previous R12199-02 model. It will be used for the completion of the KM3NeT neutrino telescope. Five hundred photomultipliers have been characterized for dark count rate, timing spread, and spurious pulses with a dedicated dark box apparatus.The results are compared with the model R12199 used in the first phase of construction of KM3NeT.

BackgroundInternational Federation of Gynecology and Obstetrics (FIGO) grade is a crucial factor in the current system for the risk stratification of endometrial endometrioid carcinoma (EC). The Cancer Genome Atlas (TCGA) demonstrated four molecular prognostic subgroups for EC: POLE (good prognosis), microsatellite-instable (MSI, intermediate prognosis), copy-number-high (CNH, poor prognosis), and copy-number-low (CNL, variable prognosis).ObjectiveTo assess how the prevalence of the TCGA molecular subgroups changes from low-grade (G1-2) to high-grade (G3) EC, to understand how it may affect the current risk-assessment system.MethodsA systematic review and meta-analysis was carried out by searching seven electronic databases from January 2013 to September 2019 for studies assessing the TCGA classification G1–2 and G3 EC. Pooled prevalence of the TCGA subgroups was calculated in EC. The association of each subgroup with grade was assessed using odds ratio (OR), with a significant p value < 0.05.ResultsNine studies with 3185 patients were included. G3 EC showed significantly higher prevalence of the POLE subgroup (12.1% vs 6.2%; OR = 2.13; p = 0.0001), of the MSI subgroup (39.7% vs 24.7%; OR = 2.15; p = 0.0003) and of the CNH subgroup (21.3% vs 4.7%; OR = 5.25; p < 0.00001), and significantly lower prevalence of the CNL subgroup (28% vs 63.5%; OR = 0.2; p < 0.00001) than G1–2 EC.ConclusionThe prevalence of the TCGA subgroups is not in accordance with the prognostic value of FIGO grade, indicating that the current risk stratification of EC will be heavily affected by molecular signature.

Background and Objectives: The type of instrumentation used during laparoscopic surgery might impact on the learning curve of resident surgeons. The aim of this study was to investigate differences in operator satisfaction and surgical outcomes between tissue sealers and classic bipolar instruments during gynecological laparoscopies performed by residents. Materials and Methods: A prospective cohort study conducted at two tertiary university hospitals between March 2019 and March 2021, on consecutive procedures: salpingo-oophorectomies (Group 1) and salpingectomies (Group 2), subdivided according to the utilized device: radiofrequency tissue sealers (Groups A1 and A2) or bipolar forceps (Groups B1 and B2). Results: 80 procedures were included. Concerning salpingo-oophorectomies, better visibility (8.4 ± 0.8 vs. 7.3 ± 0.9; p = 0.03), reduced difficulty (5.4 ± 1.2 vs. 7.0 ± 1.4; p = 0.02), improved overall satisfaction (9.2 ± 0.4 vs. 7.6 ± 1.0; p = 0.02) and reduced procedure time (7.8 ± 3.4 vs. 12.6 ± 3.1; p = 0.01) were reported by residents using tissue sealers. Intraoperative blood loss (12.2 ± 4.7 mL vs. 33.2 ± 9.7 mL; p = 0.01) and 24 h postoperative pain (4.5 ± 1.1 vs. 5.7 ± 1.8; p = 0.03) were lower in group A1 than B1. For salpingectomies, a significant reduction in duration was found in A2 compared to B2 (7.2 ± 3.4 min vs. 13.8 ± 2.2 min; p = 0.02). Tissue sealers enhanced visibility (8.1 ± 1.1 vs. 6.7 ± 1.4; p = 0.01), difficulty (6.5 ± 1.1 vs. 7.5 ± 0.9; p = 0.04) and improved satisfaction (9.3 ± 0.5 vs. 7.5 ± 0.6; p = 0.01). Moreover, hemoglobin loss and postoperative pain were reduced in A2 relative to B2 [(8.1 ± 4.2 % vs. 4.5 ± 1.1%; p = 0.02) and (5.1 ± 0.9 vs. 4.1 ± 0.8; p = 0.03), respectively] Conclusions: The use of sealing devices by residents was related to reduced difficulty as well improved visibility and overall satisfaction, with improved surgical outcomes.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our understanding of the disease. Recent investigations have unveiled the capacity of viral oncoproteins to influence epigenetic changes within HPV-related tumors, and conversely, these tumors exert an influence on the surrounding epigenetic landscape. Given the escalating occurrence of HPV-triggered tumors and the deficiency of efficacious treatments, substantial challenges emerge. A promising avenue to address this challenge lies in epigenetic modulators. This review aggregates and dissects potential epigenetic modulators capable of combatting HPV-associated infections and diseases. By delving into these modulators, novel avenues for therapeutic interventions against HPV-linked cancers have come to the fore.

Background V-betaLH is a common genetic variant of LH caused by two polymorphic base changes in the beta subunit gene, altering the amino acid sequence (Trp8Arg and Ile15Thr). In a previous-preliminary trial performed in women undergoing IVF, it was demonstrated that carriers of v-betaLH show sub-optimal ovarian response to a standard long GnRH-agonist down -regulation protocol when stimulated with pure recombinant FSH (r-hFSH). The aim of this study was to confirm the hypothesis that women with v-betaLH display hypo-sensitivity to exogenous FSH in a larger IVF population and to explore the frequency of this variant in a Danish female population. Methods In the present study, the effect of v-betaLH was retrospectively investigated in a larger series of women undergoing controlled ovarian stimulation (COS) and, for the first time, in a Danish IVF population. A total of 220 normogonadotrophic women following a long GnRH-agonist down-regulation protocol received an individualized dose of r-hFSH (100 IU and 375 IU s.c. daily) according to antral follicle count, baseline FSH, body mass index and age. The LH genotype was assessed in all patients by immunofluorometric assay. Results V-betaLH was present in 11% of patients, whereas the allelic frequency was 12%. The study population was divided into two groups according to their LH genotype. Group A consisted of 196 wt/wt women. Group B included 24 individuals with v-betaLH (21 heterozygous and 3 homozygous). No statistically significant differences in the mean number of oocytes retrieved, fertilization rate and pregnancy rate per cycle were observed between groups. However, Group B received a significantly higher cumulative-dose of r-hFSH than Group A (2435.86 +/− 932.8 IU versus 1959.8 +/− 736.45 p  = 0.048). When one-way ANOVA in a within design was applied, the LH genotype had a statistically significant effect ( p  < 0.01) on the cumulative dose of r-hFSH, showing a progressive increase from wt/wt (1959.8 +/− 736.45 IU) to v-betaLH hetero- (2267.5 +/− 824.3) and homozygotic women (3558.3 +/− 970.9). Conclusions These results confirm that carriers exhibit hypo-sensitivity to exogenous FSH during COS, documenting that the frequency of v-betaLH in Denmark is similar to a number of European countries.

Background Several studies have shown that exposure to benzene is associated to menstrual disorders, miscarriages and other disorders of the reproductive system. We performed an observational prospective pilot study to evaluate if levels of benzene in follicular fluid were correlated with response to controlled ovarian stimulation. Method Thirty-four normogonadotrophic women undergoing IVF were enrolled. Intra-follicular benzene levels were evaluated by chromatography/mass spectrometry. Based on median benzene level, we divided the study population in two groups: Group A with a “low” intra-follicular benzene concentration ( n  = 19, benzene <0.54 ng/mL) and Group B with a “high” intra-follicular benzene concentration ( n  = 15, benzene ≥ 0.54 ng/mL). The ovarian response to gonadotrophins and the outcome of IVF were analyzed in the two groups. Results The two groups did not differ in terms of demographic or anthropometric characteristics. Group B had significantly higher basal FSH levels, lower estradiol peak concentration, and fewer oocytes retrieved and embryos transferred (p < 0.05). Number of gonadotrophin vials, length of controlled ovarian stimulation and ongoing pregnancy rate were similar in the two groups. Conclusion In conclusion, ovarian response to endogenous and exogenous gonadotrophins appeared to be influenced by intra-follicular benzene levels.

l -2-Hydroxyglutaric aciduria ( l -2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. l -2-HGA is caused by mutations in the l -2-HGDH gene which most probably encodes for a l -2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting l -2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the l -2-HGDH gene found for the first time in an Italian patient affected by l -2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the l -2-HGDH gene cause l -2-HGA.

We report optical evidence of cesium (Cs) evaporation from a bialkali (SbKCs) photo-cathode during controlled heating of a photomultiplier tube (PMT). A DFB laser scanned across the 852.113 nm Cs D2 line reveals absorption features only above 60 degrees Celsius, indicating thermal desorption. The absorption correlates with temperature and offers a non-invasive method to monitor photocathode degradation in sealed detectors.