Male Infertility Diagnosis: Improvement of Genetic Analysis Performance by the Introduction of Pre-Diagnostic Genes in a Next-Generation Sequencing Custom-Made Panel

Background: Infertility affects about 7% of the general male population. The underlying cause of male infertility is undefined in about 50% of cases (idiopathic infertility). The number of genes involved in human spermatogenesis is over two thousand. Therefore, it is essential to analyze a large number of genes that may be involved in male infertility. This study aimed to test idiopathic male infertile patients negative for a validated panel of “diagnostic” genes, for a wide panel of genes that we have defined as “pre-diagnostic.” Methods: We developed a next-generation sequencing (NGS) gene panel including 65 pre-diagnostic genes that were used in 12 patients who were negative to a diagnostic genetic test for male infertility disorders, including primary spermatogenic failure and central hypogonadism, consisting of 110 genes. Results: After NGS sequencing, variants in pre-diagnostic genes were identified in 10/12 patients who were negative to a diagnostic test for primary spermatogenic failure (n = 9) or central hypogonadism (n = 1) due to mutations of single genes. Two pathogenic variants of DNAH5 and CFTR genes and three uncertain significance variants of DNAI1, DNAH11, and CCDC40 genes were found. Moreover, three variants with high impact were found in AMELY, CATSPER 2, and ADCY10 genes. Conclusion: This study suggests that searching for pre-diagnostic genes may be of relevance to find the cause of infertility in patients with apparently idiopathic primary spermatogenic failure due to mutations of single genes and central hypogonadism

Residues of 165 pesticides in citrus fruits using LC-MS/MS: a study of the pesticides distribution from the peel to the pulp

Abstract A sensitive LC–ESI-MS/MS method was developed for the determination of 165 pesticides in 50 citrus fruit samples collected in Sicily. Moreover, an evaluation of pesticides levels in the citrus layers (peel, albedo, and pulp) was carried out. The method presented acceptable trueness, precision, and linearity with LOQ of 5 μg/kg. The results obtained showed a high frequency of fungicides class pesticides in all the citrus samples examined (>95%) with the highest concentrations in the peel (4468 µg/Kg). A significant difference of concentrations was found between the layers of the citrus fruits analysed (p < 0.05). In particular, the peel and albedo present higher pesticides significantly higher than the pulp. Our findings confirming the widespread use of these substances in citrus cultivation and suggesting the importance of pesticides analysis in all the citrus fruit layers separately, considering the different interactions between the physicochemical characteristics of the matrices and the pesticides

Synthesis and pharmacological activity of 4-carbamoyl-6-beta-thienyl-4,5-dihydropyridazin-3-(2H)ones

A new series of 4-carbamoyl-6-beta-thienyl-4,5-dihydropyridazin-3-(2H)ones 4a-g have been synthesized and tested for their anti-inflammatory and analgesic properties. Among the tested compounds, only 4f at 1 mmole/Kg showed antiinflammatory activity that was comparable with that of indomethacin (5 mg/Kg) though of shorter duration. Compounds 4a, 4e and especially 4g at 0.2 mmoles/Kg displayed relevant analgesic activity, 4g being the most potent derivative in the writhing test. Compounds 4c and 4g were found to possess analgesic activity also in the hot plate test

Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism

Mutations in GBA1, the gene encoding the lysosomal enzyme β-glucocerebrosidase (GCase), which cause Gaucher's disease, are the most frequent genetic risk factor for Parkinson's disease (PD). Here, we employ global proteomic and single-cell genomic approaches in stable cell lines as well as induced pluripotent stem cell (iPSC)-derived neurons and midbrain organoids to dissect the mechanisms underlying GCase-related neurodegeneration. We demonstrate that GCase can be imported from the cytosol into the mitochondria via recognition of internal mitochondrial targeting sequence-like signals. In mitochondria, GCase promotes the maintenance of mitochondrial complex I (CI) integrity and function. Furthermore, GCase interacts with the mitochondrial quality control proteins HSP60 and LONP1. Disease-associated mutations impair CI stability and function and enhance the interaction with the mitochondrial quality control machinery. These findings reveal a mitochondrial role of GCase and suggest that defective CI activity and energy metabolism may drive the pathogenesis of GCase-linked neurodegeneration

Water planning and management in the Cornia river plain by means of the gis-integrated freewat platform

Coastal aquifer, Cornia valley, Tuscany, Managed Aquifer Recharge, FREEWAT platform

Using flood water in Managed Aquifer Recharge schemes as a solution for groundwater management in the Cornia valley (Italy)

The lower Cornia valley aquifer system (Tuscany, Italy) provides the only source of water for drinking, irrigation, industrial purposes and it also contributes to the water needs of the nearby Elba island. Since 60 years, intensive exploitation of groundwater resulted in consistent head lowering and water balance deficit, causing subsidence, reduction of groundwater dependent ecosystems, and salinization of freshwater resources. Rebalancing the water budget of the hydrologic system is the main objective of the LIFE REWAT project (sustainable WATer management in the lower Cornia valley through demand REduction, aquifer Recharge and river REstoration; http://www.liferewat.eu). Here, five demonstration measures (river restoration; Managed Aquifer Recharge; reuse of treated wastewater for irrigation; high irrigation efficiency scheme; leakage management in water distribution systems) are set in place for promoting water resource management, along with capacity building and participatory actions. A pilot Managed Aquifer Recharge (MAR) infiltration basin for using flood-water was designed and set in operation in Suvereto, testing the new-issued Italian regulation on artificial recharge of aquifers (DM 100/2016). The infiltration basin is located at a pre-existing topographical low near the Cornia River. The river, having intermittent flow, provides the recharge water during high flow periods, including floods, and when discharge is above the minimum ecological flow. The infiltration basin is set in a groundwater recharge area where the aquifer is constituted by gravel and sands. A preliminary project and an executive one were prepared and discussed with the relevant authorities, following one-year long monthly monitoring of surface- and ground-water. The project was supported by a groundwater flow modelling-based approach using the FREEWAT platform (www.freewat.eu). The facility consists of the following elements: i) intake work on the River Cornia; ii) the inlet structure control system, managed by quality (mass spectrometer defining surface water spectral signature) and level probes, and allowing pumping into the facility at predefined head and chemical quality thresholds; iii) a sedimentation basin; iv) the infiltration area (less than 1 ha large); v) the operational monitoring system, based on a network of piezometers where both continuous data (head, T, EC, DO) are gathered and discrete measurements/sampling performed. The cost of construction of the plant is about 300000 C well below the cost of a surface water reservoir for a similar storage. Depending on the climatic conditions, the estimated volume of diverted surface water may vary between 300000 m3/year and 2 Mm3/year. Being the facility a pilot one, diverted water discharge ranges between 20 to 50 l/s. Minimal site development and modification was required, resulting in a no-impact water-work, while providing ecosystem benefits by reconnecting and inundating former abandoned riverbeds. The effectiveness of such pilot may demonstrate the potential for Flood-MAR schemes to increase water availability in scarcity prone areas

Dietary intake of animal and plant proteins and risk of all cause and cause-specific mortality: The Epic-Italy cohort

BACKGROUND: To examine the associations of animal and plant protein intake with all-cause, cardiovascular and cancer mortality risk in middle-aged Italian men and women with substantially lower animal protein intake than North Americans. METHODS AND RESULTS: Food consumption was assessed by validated Epic semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex, and adjusted for confounders, estimated associations of animal and plant protein consumption with mortality for all causes, cardiovascular disease, and cancer. After a median follow-up of 15.2 years, 2,449 deaths were identified in 45,009 participants. No significant association between intake of total, animal or plant protein and mortality was found in the fully adjusted models. Substitution of plant protein for animal protein was inversely associated with cardiovascular mortality (HR, 0.47; 95% CI, 0.24–0.92) only in people with at least 1 unhealthy lifestyle risk factor and poor adherence to a Mediterranean diet. Participants in the highest quintile group of animal protein intake had higher glucose, total and LDL cholesterol levels than those in the lowest quintile. In contrast, higher plant protein intake was negatively associated with fasting insulin and cholesterol, despite higher BMI, physical inactivity and starch consumption. CONCLUSIONS: Replacing plant protein for animal protein was associated with lower cardiovascular mortality among individuals with unhealthy lifestyle risk factors. High animal but not plant protein intake is associated with impaired fasting glucose and hypercholesterolemia, despite lower calorie and carbohydrate intake, suggesting that protein source plays crucial roles in modulating cardiometabolic health independently of body weight

Treating People With Epilepsy in Rural Low-Income Countries Is Feasible. Observations and Reflections From a “Real Life Experience” After a Long Lasting Intervention in the Rural Chaco

Introduction: Epilepsy represents an important public health issue, in particular in low and middle-income countries where significant disparities are present in the care available for patients with epilepsy. Treatment cost and unavailability of drugs represent important barriers in treating people with epilepsy especially in rural setting. Aim of the study was to evaluate, by means of routine data, the current real-life clinical practice in epilepsy in the rural communities of the Plurinational State of Bolivia. Treatment activity followed educational campaigns and an anthropological fieldwork over more than 20 years.Material and Methods: Medical records of people with epilepsy (PWE) living in the rural communities of the Bolivian Chaco who received antiepileptic drugs (AEDs), from 2012 to 2016, and were followed-up for at least 1 year were analyzed. Treatment delivery and follow up visits were managed by a neurologist with the support of rural health care workers.Results: From 2012 to 2016, 157 PWE (76 men with a mean age of 24.2 ± 15.7) have been included in the study. Structural epilepsy was the most common type, recorded in 54 cases (34.4%) and the most common reported causes were perinatal factors, present in 11 subjects (20.0%). Almost all patients presented epilepsy with generalized tonic-clonic seizures (91.4%). The most common AED prescribed was phenobarbital followed by carbamazepine. During the follow-up, a dramatic seizures reduction was observed, with 31 subjects (19.7%) being seizures-free at the last follow-up. However, 48 subjects (30.6%) did not assume the medication regularly and 10 interrupted the drug intake. More than 20% of PWE did not receive any financial supports for AEDs. During the follow-up period 10 patients died but only in one case the death was probably caused by epilepsy.Conclusion: Our study demonstrated that PWE in rural areas of the Bolivian Chaco are willing to seek medical attention and to receive antiepileptic treatment. However, improvement in care is needed to assure compliance to AED treatment, including activity to increase awareness toward epilepsy among community members and health staff of the rural communities and to guarantee the coverage of treatment costs and drug supply

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016–September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy

Integration of art and technology in personalized radiation oncology care: Experiences, evidence, and perspectives

Cancer diagnoses expose patients to traumatic stress, sudden changes in daily life, changes in the body and autonomy, with even long-term consequences, and in some cases, to come to terms with the end-of-life. Furthermore, rising survival rates underline that the need for interventions for emotional wellbeing is in growing demand by patients and survivors. Cancer patients frequently have compliance problems, difficulties during treatment, stress, or challenges in implementing healthy behaviors. This scenario was highlighted during the COVID-19 emergency. These issues often do not reach the clinical attention of dedicated professionals and could also become a source of stress or burnout for professionals. So, these consequences are evident on individual, interpersonal, and health system levels. Oncology services have increasingly sought to provide value-based health care, considering resources invested, with implications for service delivery and related financing mechanisms. Value-based health care can improve patient outcomes, often revealed by patient outcome measures while seeking balance with economical budgets. The paper aims to show the Gemelli Advanced Radiation Therapy (ART) experience of personalizing the patients' care pathway through interventions based on technologies and art, the personalized approach to cancer patients and their role as “co-stars” in treatment care. The paper describes the vision, experiences, and evidence that have guided clinical choices involving patients and professionals in a co-constructed therapeutic pathway. We will explore this approach by describing: the various initiatives already implemented and prospects, with particular attention to the economic sustainability of the paths proposed to patients; the several pathways of personalized care, both from the patient's and healthcare professional perspective, that put the person's experience at the Gemelli ART Center. The patient's satisfaction with the treatment and economic outcomes have been considered. The experiences and future perspectives described in the manuscript will focus on the value of people's experiences and patient satisfaction indicators, patients, staff, and the healthcare organization