Search Results (17)

Congenital hypogonadotropic hypogonadism (CHH) is a rare and heterogeneous genetic disorder with variable penetrance caused by GnRH deficiency, leading to delayed puberty and infertility. In 50–60% of cases, CHH is associated with non-reproductive abnormalities, most commonly anosmia/hyposmia (Kallmann syndrome, KS). Over 60 genes have been implicated in CHH pathogenesis. We aimed to perform genetic screening in a cohort of 14 patients (10 males, 4 females; mean age 22 ± 7.72 years) with suspected or diagnosed HH/KS. Genetic analysis was conducted using next-generation sequencing (NGS) with a custom panel of 46 candidate genes. Variant interpretation followed ACMG standards and guidelines. Multiple tools were used to predict the structural effects of variants on tertiary protein structure, assessing their pathogenicity. Novel variants were functionally characterized by qRT-PCR on mRNA extracted from peripheral leukocytes. NGS identified nine rare variants and four novel variants in genes previously associated with normosmic isolated HH (nHH) and/or KS (FGFR1, PROK2, TAC3R, DCC, WDR11, IL17RD, DUSP6, KAL1, FGF8, IL17RD and DCC). The variant in TAC3R (p.Trp275Ter) was pathogenic; variants in ANOS1 (c.541+1G>A), IL17RD (c.1303_1304dup, p.Lys436ThrfsTer58), and TAC3R (p.Lys361Ter) were likely pathogenic. Nine variants were classified as variants of uncertain significance (VUS). Our study identified a possible genetic cause in 71% of the CHH/KS cohort, emphasizing the importance of genetic screening and functional characterization of genetic variants in patients with a phenotypically and genetically heterogeneous disorder like CHH. Full article

The prevalence of skin aging and the request for effective treatments have driven dermatological research towards natural solutions. This study investigates the anti-aging efficacy of two bioactive natural polyphenols, Oleocanthal and Oleacein, in a skincare formulation. A single-blind, randomized clinical trial involved 70 participants, using a comprehensive exclusion criterion to ensure participant safety and study integrity. Participants applied the Oleocanthal and Oleacein 1% serum formulation twice daily for 30 days. The efficacy was objectively assessed using the VISIA^® Skin Analysis System at baseline, after 15 days, and after 30 days. Results indicated significant wrinkle reduction in most groups. For women aged 45–79 years, the mean change was −33.91% (95% CI: −46.75% to −21.07%). For men aged 20–44 years, it was −51.93% (95% CI: −76.54% to −27.33%), and for men aged 45–79 years, it was −46.56% (95% CI: −58.32% to −34.81%). For women aged 20–44 years, the change was −25.68% (95% CI: −63.91% to 12.54%), not statistically significant. These findings highlight the potential of EVOO-derived polyphenols in anti-aging skincare, particularly for older adults. This research paves the way for further exploration into natural compounds in dermatology, particularly for aging skin management. Full article

We compared the perioperative outcomes of open (ORC) vs. robot-assisted (RARC) radical cystectomy in the treatment of pT4a MIBC. In total, 212 patients underwent ORC (102 patients, Group A) vs. RARC (110 patients, Group B) for pT4a bladder cancer. Patients were prospectively followed and retrospectively reviewed. We assessed operative time, estimated blood loss (EBL), intraoperative and postoperative complications, length of stay, transfusion rate, and oncological outcomes. Preoperative features were comparable. The mean operative time was 232.8 vs. 189.2 min (p = 0.04), and mean EBL was 832.8 vs. 523.7 mL in Group A vs. B (p = 0.04). An intraoperative transfusion was performed in 32 (31.4%) vs. 11 (10.0%) cases during ORC vs. RARC (p = 0.03). The intraoperative complications rate was comparable. The mean length of stay was shorter after RARC (12.6 vs. 7.2 days, p = 0.02). Postoperative transfusions were performed in 36 (35.3%) vs. 13 (11.8%) cases (p = 0.03), and postoperative complications occurred in 37 (36.3%) vs. 29 (26.4%) patients in Groups A vs. B (p = 0.05). The positive surgical margin (PSM) rate was lower after RARC. No differences were recorded according to the oncological outcomes. ORC and RARC are feasible treatments for the management of pT4a bladder tumors. Minimally invasive surgery provides shorter operative time, bleeding, transfusion rate, postoperative complications, length of stay, and PSM rate. Full article

Background: West Nile virus (WNV) is an emerging mosquito-borne neurotropic virus, belonging to the Flaviviridae family and the Orthoflavivirus genus. The effective control of WNV requires a targeted preventive strategy that also needs the identification of the higher-risk populations. Hence, this study focused on a systematic literature review of WNV-acquired infection in work-related settings and the assessment of the exposure risks among different occupational categories. Methods: A comprehensive search was conducted to identify studies until September 2023 in multiple databases such as PubMed/MEDLINE, SCOPUS and Web of Science, according to the PRISMA 2020 statement. Risk of bias of collected papers was assessed by the ROB tool of the National Toxicology Program’s Office of Health Assessment and Translation handbook. Results: A total of 21 studies were included in the systematic review, out of which seventeen were observational studies and four were case reports. Workers identified as at higher risk for WNV infection were military workers, veterinarians, agricultural workers, farmers, and laboratory workers with contact with infected fluids or aerosols. Conclusions: The identification of higher-risk workers could facilitate active surveillance by occupational physicians, which could improve our understanding of the epidemiology of WNV and, in addition, could help tailor appropriate preventive recommendations, reducing the overall burden of disease in high-risk areas. Full article

Deep sequencing has revealed that the 16S rRNA gene composition of the human microbiome can vary between populations. However, when existing data are insufficient to address the desired study questions due to limited sample sizes, Dirichlet mixture modeling (DMM) can simulate 16S rRNA gene predictions from experimental microbiome data. We examined the extent to which simulated 16S rRNA gene microbiome data can accurately reflect the diversity within that identified from experimental data and calculate the power. Even when experimental and simulated datasets differed by less than 10%, simulation by DMM consistently overestimates power, except when using only highly discriminating taxa. Admixtures of DMM with experimental data performed poorly compared to pure simulation and did not show the same correlation with experimental data p-value and power values. While multiple replications of random sampling remain the favored method of determining the power, when the estimated sample size required to achieve a certain power exceeds the sample number, then simulated samples based on DMM can be used. We introduce an R-Package, MPrESS, to assist in power calculation and sample size estimation for a 16S rRNA gene microbiome dataset to detect a difference between populations. MPrESS can be downloaded from GitHub. Full article

Metabolites are intermediates or end products of biochemical processes involved in both health and disease. Here, we take advantage of the well-characterized Cooperative Health Research in South Tyrol (CHRIS) study to perform an exome-wide association study (ExWAS) on absolute concentrations of 175 metabolites in 3294 individuals. To increase power, we imputed the identified variants into an additional 2211 genotyped individuals of CHRIS. In the resulting dataset of 5505 individuals, we identified 85 single-variant genetic associations, of which 39 have not been reported previously. Fifteen associations emerged at ten variants with >5-fold enrichment in CHRIS compared to non-Finnish Europeans reported in the gnomAD database. For example, the CHRIS-enriched ETFDH stop gain variant p.Trp286Ter (rs1235904433-hexanoylcarnitine) and the MCCC2 stop lost variant p.Ter564GlnextTer3 (rs751970792-carnitine) have been found in patients with glutaric acidemia type II and 3-methylcrotonylglycinuria, respectively, but the loci have not been associated with the respective metabolites in a genome-wide association study (GWAS) previously. We further identified three gene-trait associations, where multiple rare variants contribute to the signal. These results not only provide further evidence for previously described associations, but also describe novel genes and mechanisms for diseases and disease-related traits. Full article

Objective: To assess whether varicocele affects testicular 25-hydroxylase activity. Methods: Twenty normozoospermic patients with bilateral varicocele (grade III according to the Dubin and Amelar classification) without indications to undergo varicocele repair (normal sperm parameters and testicular volume; no scrotal pain) were consecutively enrolled and followed-up for four years. Serum levels of parathyroid hormone (PTH), calcium, and 25-hydroxy-cholecalciferol [25(OH)D] along with serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), conventional sperm parameters, sperm DNA fragmentation (SDF) rate, and testicular volume (TV) were measured annually for three years. PTH, calcium, and 25(OH)D serum levels over time were compared with those of age- and body mass index (BMI)-matched control group of twenty varicocelectomized patients. Main results: Both intra- and between-group analyses showed that serum PTH levels increased significantly over time in parallel with a significant decline in 25(OH)D levels. Serum calcium levels did not change significantly. At the same time, signs of mild Leydig and Sertoli cell dysfunction were found, such as an increase in gonadotropins and decreased TT and VT. However, conventional sperm parameters and SDF rate did not change significantly. Conclusion: This prospective controlled study provides the first evidence of a negative impact of bilateral grade III varicocele on testicular 25-hydroxylase activity. Accordingly, the patients included in this study showed a significant increase in PTH and a decrease in 25(OH)D levels over time. Patients with varicocele deserve endocrinologic counseling. Full article

In this paper, we report a multiscale investigation of the compositional, morphological, structural, electrical, and optical emission properties of 2H-MoS₂ obtained by sulfurization at 800 °C of very thin MoO₃ films (with thickness ranging from ~2.8 nm to ~4.2 nm) on a SiO₂/Si substrate. XPS analyses confirmed that the sulfurization was very effective in the reduction of the oxide to MoS_2, with only a small percentage of residual MoO₃ present in the final film. High-resolution TEM/STEM analyses revealed the formation of few (i.e., 2–3 layers) of MoS₂ nearly aligned with the SiO₂ surface in the case of the thinnest (~2.8 nm) MoO₃ film, whereas multilayers of MoS₂ partially standing up with respect to the substrate were observed for the ~4.2 nm one. Such different configurations indicate the prevalence of different mechanisms (i.e., vapour-solid surface reaction or S diffusion within the film) as a function of the thickness. The uniform thickness distribution of the few-layer and multilayer MoS₂ was confirmed by Raman mapping. Furthermore, the correlative plot of the characteristic A_1g-E_2g Raman modes revealed a compressive strain (ε ≈ −0.78 ± 0.18%) and the coexistence of n- and p-type doped areas in the few-layer MoS₂ on SiO₂, where the p-type doping is probably due to the presence of residual MoO₃. Nanoscale resolution current mapping by C-AFM showed local inhomogeneities in the conductivity of the few-layer MoS₂, which are well correlated to the lateral changes in the strain detected by Raman. Finally, characteristic spectroscopic signatures of the defects/disorder in MoS₂ films produced by sulfurization were identified by a comparative analysis of Raman and photoluminescence (PL) spectra with CVD grown MoS₂ flakes. Full article

Background: Selenium (Se) is an essential component of selenoenzymes, which have catalytic and antioxidant functions. A low Se status has been reported in patients with chronic autoimmune thyroiditis (AT) who benefit from Se supplementation. The role of Se in male reproduction is still a matter of debate. Although Se and selenoenzymes ensure sperm viability and protect against increased oxidative stress, only a few studies have assessed the effects of the administration of Se alone on sperm parameters, providing contrasting results. Aim: The aim of this study was to assess the effects of oral Se supplementation on conventional sperm parameters and DNA fragmentation (SDF) in patients with AT of reproductive age with normal thyroid function. Patients and Methods: Only patients with AT and normal thyroid function were selected for this study. All included patients underwent oral Se supplementation at the dose of 83 µg once daily (Syrel^®, IBSA) for six months. Sperm conventional parameters, SDF, and thyroid function were assessed before and at the end of the treatment. Results: Twenty AT patients with normal weight were enrolled. After Se supplementation, they showed a higher sperm concentration, a higher percentage of sperm with progressive motility, and a higher percentage with normal morphology. They also had lower semen leukocyte concentration, and a lower percentage of spermatozoa with DNA fragmentation compared with pre-treatment values. Free-thyroxine serum levels increased significantly, whereas free triiodothyronine showed an upward trend. The thyroid-stimulating hormone did not change significantly. Conclusion: Se supplementation may represent a possible non-hormonal therapeutic choice for the treatment of male infertility, although further studies are needed to confirm this evidence. The possible thyroid hormone dependency of these findings needs to be clarified. Full article

Follicle-stimulating hormone (FSH) is a therapeutic option in patients with idiopathic oligozoospermia and normal FSH serum levels. However, few studies have evaluated which dose of FSH is more effective. The aim of this study was to compare the clinical efficacy of the two most frequently used FSH treatment regimens: 75 IU daily vs. 150 IU three times a week. Patients were retrospectively assigned to two groups. The first group (n = 24) was prescribed highly purified FSH (hpFSH) 75 IU/daily (Group A), and the second group (n = 24) was prescribed hpFSH 150 IU three times a week (Group B) for three months. Before and after treatment, each patient underwent semen analysis, evaluation of the percentage of DNA-fragmented spermatozoa, assessment of testicular volume (by ultrasonography), and measurement of FSH and total testosterone (TT) serum levels. Treatment with hpFSH significantly improved conventional sperm parameters. In detail, sperm concentration increased significantly after treatment only in Group A, whereas total sperm count, percentage of spermatozoa with progressive motility, normal morphology, or alive improved significantly in both groups. Interestingly, the percentage of sperm DNA fragmentation decreased significantly in both groups after treatment with hpFSH. FSH serum levels were expectably higher at the end of the treatment than before hpFSH was administered to both groups. Remarkably, TT serum levels only increased significantly in Group A. Finally, testicular volume was significantly higher in Group A after treatment, while it did not change significantly compared to baseline in Group B. The percentage of FSH responders did not differ significantly between the two groups (8/24 vs. 6/24). The daily administration of hpFSH 75 IU seems more effective than using 150 IU three times a week. However, this therapeutic scheme implies a higher number of injections and slightly higher costs. Full article

The University of Pavia owns an extensive real estate portfolio, largely consisting of historic buildings still hosting teaching and research activities. This implies a continuous challenge in keeping them efficient, sustainable and completely usable. Indeed, these heritage buildings, alongside an undeniable charm, bring with them deficiencies regarding safety, accessibility, energy efficiency, etc. This work presents an interdisciplinary strategy addressing the issues involved in the management of the multiple needs of conservation and use, complying with modern standards. The legal requirement of a seismic safety assessment was the occasion to launch a comprehensive review of the state of the University building heritage, considering together the different aspects involved, in a perspective of economic sustainability, combining preservation needs and valorisation. The steps of this strategy included a preliminary screening of all the buildings, by simple methods and tools. The aim was to gather homogeneous and comparable information, useful to identify critical structures and/or repeated issues, to allocate resources for deeper analyses and implementation. The case study of San Felice Palace, which presents emblematic features and deficiencies, is illustrated in more detail, with complete seismic safety and accessibility analyses leading to proposals of enhancement interventions. Full article

The focus of this study was to investigate the efficacy of applying boron-doped diamond (BDD) electrodes in an electrochemical advanced oxidation process, for the removal of the target compound diclofenac (DCF) in different water matrices. The reduction of DCF, and at the same time the formation of transformation products (TPs) and inorganic by-products, was investigated as a function of electrode settings and the duration of treatment. Kinetic assessments of DCF and possible TPs derived from data from the literature were performed, based on a serial chromatographic separation with reversed-phase liquid chromatographyfollowed by hydophilic interaction liquid chromatography (RPLC-HILIC system) coupled to ESI-TOF mass spectrometry. The application of the BDD electrode resulted in the complete removal of DCF in deionized water, drinking water and wastewater effluents spiked with DCF. As a function of the applied current density, a variety of TPs appeared, including early stage products, structures after ring opening and highly oxidized small molecules. Both the complexity of the water matrix and the electrode settings had a noticeable influence on the treatment process’s efficacy. In order to achieve effective removal of the target compound under economic conditions, and at the same time minimize by-product formation, it is recommended to operate the electrode at a moderate current density and reduce the extent of the treatment. Full article

Can the coffee berry borer (Hypothenemus hampei, or CBB) use host plants other than coffee for food and shelter? The use of fruits other than coffee has been reported. However, the validity of these reports depends on accurate identification of CBB, which is sometimes uncertain. In this study we sampled potential alternate hosts in coffee farms in Puerto Rico. Fruits with perforations were collected and examined for the presence of scolytid beetles (Coleoptera: Curculionidae: Scolytinae). Scolytids were identified by morphology and DNA barcoding of the COI gene. Association between the presence of Inga vera and Guarea guidonia trees and infestation rate of CBB in coffee fruits was evaluated. Food preference tests were performed in the laboratory. A total of 3563 beetles were found and 587 were identified as Hypothenemus spp.; of these, 85 identifications were confirmed by DNA barcoding. Twenty-seven of the beetles identified were H. hampei, mostly in I. vera fruits in periods between coffee crops. Most scolytids identified were H. obscurus. In preference tests, some CBB initially penetrated G. guidonia fruits, but eventually chose coffee. There was no evidence of feeding or reproduction in fruits of G. guidonia or Cajanus cajan. The results show that in Puerto Rico it is rare to find CBB in fruits of alternate hosts. The scarcity of coffee fruits in the off-season might cause some CBBs to take refuge in other fruits, but they did not feed or reproduce in them in laboratory tests. Understanding the refugia of CBB in the off-season may be useful for designing effective management strategies. Full article

(1) Background: This study aimed to compare the incidence of tactical principles, the percentage of successful tactical principles, and the network properties between higher and lower aerobic power in young football players during small-sided games. (2) Methods: Eighteen Under-17 Brazilian players were recruited. Firstly, they performed the Yo-Yo Intermittent Recovery Test Level 2, which was used to split them into two groups with higher and lower aerobic power. In the sequence, they played three vs three small-sided games within each group. The System of Tactical Assessment in Soccer was used to analyze the tactical behavior demonstrated by measuring the incidence of tactical principles and the percentage of successful principles, while the macro variables, density and clustering coefficient from social network analysis for team sports was used to analyze players’ interactions. (3) Results: No differences were reported for the incidence of tactical principles (p > 0.05, small or small-to-moderate effect sizes), the percentage of successful offensive principles (p = 0.122, small-to-moderate effect size), or the network variables (p > 0.05; small effect sizes). The lower aerobic power group demonstrated a higher percentage of successful defensive tactical principles (p = 0.043; small-to-moderate effect size). (4) Conclusions: We concluded that aerobic power has a limited impact on player behavior, indicating that players’ actions within a small-sided game are mostly constrained by other parameters. Full article

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) constitutes an emerging health problem for companion animals in veterinary medicine. Therefore, discovery of novel antimicrobial agents for treatment of Staphylococcus-associated canine infections is urgently needed to reduce use of human antibiotics in veterinary medicine. In the present work, we characterized the antimicrobial activity of the peptoid D2 against S. pseudintermedius and Pseudomonas aeruginosa, which is another common integumentary pathogen in dogs. Furthermore, we performed a structure–activity relationship study of D2, which included 19 peptide/peptoid analogs. Our best compound D2D, an all d-peptide analogue, showed potent minimum inhibitory concentrations (MICs) against canine S. pseudintermedius (2–4 µg/mL) and P. aeruginosa (4 µg/mL) isolates as well as other selected dog pathogens (2–16 µg/mL). Time–kill assays demonstrated that D2D was able to inhibit MRSP in 30 min at 1× MIC, significantly faster than D2. Our results suggest that at high concentrations D2D is rapidly lysing the bacterial membrane while D2 is inhibiting macromolecular synthesis. We probed the mechanism of action at sub-MIC concentrations of D2, D2D, the l-peptide analog and its retro analog by a macromolecular biosynthesis assay and fluorescence spectroscopy. Our data suggest that at sub-MIC concentrations D2D is membrane inactive and primarily works by cell wall inhibition, while the other compounds mainly act on the bacterial membrane. Full article