Effectiveness of near-infrared spectroscopy to predict the chemical composition of feces and total-tract apparent nutrients digestibility estimated with undigestible neutral detergent fiber or acid-insoluble ash in lactating buffaloes' feces.

Following a comparison of nutrient total-tract digestibility estimates in lactating buffaloes using single-point undigestible NDF (uNDF) or acid-insoluble ash (AIA) as internal markers, the potential of fecal near-infrared spectroscopy (NIRS) to provide calibration equations for the assessment of the chemical composition of feces and nutrient total-tract digestibility estimated with internal markers was explored. Chemical analyses were performed on 147 fecal samples from lactating buffaloes reared on 5 farms in central Italy (Naples). Each farm fed a silage-based TMR to the buffaloes, and the TMR was sampled in the 2 d before the fecal collection. The TMR and individual fecal samples were collected and analyzed for DM, OM, ash, AIA, ether extract (EE), starch, fiber fractions (amylase-treated NDF without residual ash [aNDFom], amylase-treated NDF inclusive of residual ash [aNDF], ADF without residual ash [ADFom], ADF, hemicellulose, cellulose, ADL, uNDF), N, CP and CP bound to aNDF (NDICP) and to ADF (ADICP). The uNDF content was determined through a 240-h in vitro fermentation and employed, together with AIA as markers, to estimate the total-tract apparent digestibility and total-tract digestibility of DM, OM, ash, N, CP, EE, aNDFom, aNDF, NDIP, ADFom, and ADF, ADIN, ADL, hemicellulose, cellulose, starch, NFC, and the B3 fraction of N (NB3). No correlation was found between DM and OM digestibility estimated with AIA and uNDF as internal markers. Weak correlations were detected for all the other nutients digestibilities, and strong correlations were observed for EE, ADFom, hemicellulose, NDIN, ADIN, NB3, NFC, and starch. The sample set (n = 147) was divided in a calibration set (n = 111) and a validation set (n = 36) to "train" and "validate" the fecal NIRS curve through an external validation process. An estimation usable for preliminary or initial evaluation was obtained for N, CP, and aNDF fecal content. An excellent prediction was obtained for total tract digestibility of ADIN (R2 = 0.90) when estimated with uNDF as the internal marker. The NIRS technology was not able to accurately predict all the other traits and the estimated nutrient digestibility of lactating buffalo diets from fecal spectra.

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people.

PURPOSE: Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety. METHODS: A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events. RESULTS: Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits' number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups. CONCLUSION: Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.

A short-term comparison of wheat straw and poplar wood chips used as litter in tiestalls on hygiene, milk, and behavior of lactating dairy cows.

A short-term study was conducted to compare the effect of using poplar wood chips (PWC) instead of wheat straw (WS) litter in dairy cows. A total of 38 lactating Holstein cows (204 ± 119 days in milk, 26.9 ± 6.5 kg of milk yield [MY]) were housed in a tiestall farm for a 10-d trial including 5 d of adaptation followed by 5 sampling days (from d 5 to 10). Cows were divided into 2 homogeneous groups: one group was bedded with WS, and the second with PWC. Both litter materials were provided in the amount of 7 kg/stall per d. Each group was composed of 3 subgroups of 6 or 7 cows; the subgroups were physically separated along the feeding line by wooden boards. During the sampling days, fecal composition, used litter composition, and bacterial count (Clostridium spp., Salmonella spp., Escherichia coli, Lactobacillus, and total bacterial count) were analyzed by subgroup twice a day. On d 1 and from d 5 to 10, udder hygiene score and cow cleanliness score were also evaluated individually twice a day. Meanwhile MY, milk hygiene (total bacterial count [TBC], coliform bacterial count [CBC], and spore-forming units [SFU]) and quality were measured and analyzed from 9 animals per group. Moreover, individual animal behavior (body position and behavioral traits) and subgroup dry matter intake were measured on d 9 and 10. Fecal dry matter did not differ between groups, PWC had the lowest used litter moisture and N content favoring the highest clean cow frequency, but also gave rise to the greatest used litter microbial contamination. The MY, milk quality, TBC, SFU, and CBC were similar. The lying behavior frequency was similar between groups. However, the PWC group showed the lowest sleeping frequency, the highest frequency of other behaviors (including discomfort signs), and the lowest dry matter intake. However, despite this apparent reduction in cow comfort, no biologically important differences were observed in this short-term study between cows on PWC and WS in milk production or hygiene.

Characterization and optimization of a ß detector for 18F radio-guided surgery.

Radio-Guided Surgery (RGS) is a nuclear medicine technique to support the surgeon during surgery towards a complete tumor resection. It is based on intraoperative detection of radiation emitted by a radio-pharmaceutical that bounds selectively to tumoral cells. In the past years, an approach that exploits ß- emitting radiotracers has been pursued to overtake some limitations of the traditional RGS based on γ emission. A particle detector dedicated to this application, demonstrating very high efficiency to ß- particles and remarkable transparency to photons, has been thus developed. As a by-product, its characteristics suggested the possibility to utilize it with ß+ emitting sources, more commonly in use in nuclear medicine. In this paper, performances of such detector on 18F liquid sources are estimated by means of Monte Carlo simulations (MC) and laboratory measurements. The experimental setup with a 18F saline solution comprised a "positron signal" spot (a 7 × 10 mm cylinder representing the tumor residual), and a surrounding "far background" volume, that represented for the detector an almost isotropic source of annihilation photons. Experimental results show good agreement with MC predictions, thus confirming the expected performances of the detector with 18F, and the validity of the developed MC simulation as a tool to predict the gamma background determined by a diffuse source of annihilation photons.

A network meta-analysis of the impact of feed-grade and slow-release ureas on lactating dairy cattle.

A network meta-analysis was conducted to determine the effects of feeding feed-grade urea (FGU) or slow-release urea (SRU) as a replacement for true protein supplements (control; CTR) in high-producing dairy cattle diets. Research papers were selected (n = 44) from experiments published between 1971 and 2021 based on the following criteria: dairy breed, detailed description of the isonitrogenous diets fed, provision of FGU or SRU (or both), high-yielding cows (>25 kg/cow per day), and results that included at least milk yield and composition, but data on nutrient intake, digestibility, ruminal fermentation profile, and N utilization were also considered. Most studies compared only 2 treatments, and a network meta-analysis approach was adopted to compare the effects among CTR, FGU, and SRU. Data were analyzed using a generalized linear mixed model network meta-analysis. Forest plots of milk yield were used to visualize the estimated effect size of treatments. Cows included in the study produced 32.9 ± 5.7 L/d of milk, 3.46 ± 5.0% of fat, and 3.11 ± 0.2% of protein with an intake of 22.1 ± 3.45 kg of dry matter. Average diet composition was 1.65 ± 0.07 Mcal of net energy for lactation, 16.4 ± 1.45% CP, 30.8 ± 5.91% neutral detergent fiber, and 23.0 ± 4.62% starch. Average supply of FGU was 209 g/cow per day, whereas the average supply of SRU was 204 g/cow per day. With some exceptions, feeding FGU and SRU did not affect nutrient intake and digestibility, N utilization, and milk yield and composition. However, the FGU reduced the acetate proportion (61.6 vs. 59.7 mol/100 mol) and the SRU reduced the butyrate proportion (12.4 vs. 11.9 mol/100 mol) compared with CTR. Ruminal ammonia-N concentration increased from 8.47 to 11.5 and 9.3 mg/dL in CTR, FGU, and SRU, respectively. Urinary nitrogen excretion increased from 171 to 198 g/d in CTR versus the 2 urea treatments, respectively. The use of moderate doses of FGU in high-producing dairy cows may be justified based on its lower cost.

Effects of the addition of non-fibre carbohydrates with different rumen degradation rates in dairy cow high-forage diets using the Rumen Simulation Technique.

Nutrient synchronisation of protein and carbohydrates is a promising practice to improve ruminal nutrient utilisation. However, dietary sources supplying these nutrients can vary in ruminal nutrient availability due to differing degradation rates, therefore potentially affecting utilisation of nitrogen (N). The effects of the addition of non-fibre carbohydrates (NFCs) with different rumen degradation rates in high-forage diets on ruminal fermentation, efficiency and microbial flow were investigated in vitro using the Rumen Simulation Technique (RUSITEC). Four diets were tested: control with 100% ryegrass silage (GRS) and substitution of 20% on a DM basis of ryegrass silage with corn grain (CORN), processed corn (OZ) or sucrose (SUC). The four diets were assigned to 16 vessels in two sets of RUSITEC apparatuses in a randomised block design over a 17 d experimental trial; 10 d consisted of adaptation and 7 d for sample collection. Rumen fluid was collected from four rumen-cannulated dry Holstein-Friesian dairy cows and was treated without mixing. Then, rumen fluid from each cow was used to inoculate four vessels, and diet treatments were randomly allocated to each one. This was repeated for all cows resulting in 16 vessels. The inclusion of SUC in ryegrass silage diets improved DM and organic matter digestibility. The only diet to significantly lower ammonia-N concentration compared with GRS was SUC. The outflows of non-ammonia-N, microbial-N, and efficiency of microbial protein synthesis were not affected by diet type. However, the efficiency of nitrogen utilisation was improved by SUC compared with GRS. This indicates that the inclusion of an energy source with a high rumen degradation rate in high-forage diets improves rumen fermentation, digestibility, and N utilisation. Specifically, this effect was observed for the more readily available energy source, SUC, compared with the more slowly degradable NFC sources, CORN and OZ.

Long-term trajectories of bone metabolism parameters and bone mineral density (BMD) in obese patients treated with metabolic surgery: a real-world, retrospective study.

PURPOSE: Potential negative effects of metabolic surgery on skeletal integrity remain a concern, since long-term data of different surgical approaches are poor. This study aimed to describe changes in bone metabolism in subjects with obesity undergoing both Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: A single center, retrospective, observational clinical study on real-world data was performed enrolling subjects undergoing metabolic surgery. RESULTS: 123 subjects were enrolled (males 31: females 92; ages 48.2 ± 7.9 years). All patients were evaluated until 16.9 ± 8.1 months after surgery, while a small group was evaluated up to 4.5 years. All patients were treated after surgery with calcium and vitamin D integration. Both calcium and phosphate serum levels significantly increased after metabolic surgery and remained stable during follow-up. These trends did not differ between RYGB and SG (p = 0.245). Ca/P ratio decreased after surgery compared to baseline (p < 0.001) and this decrease remained among follow-up visits. While 24-h urinary calcium remained stable across all visits, 24-h urinary phosphate showed lower levels after surgery (p = 0.014), also according to surgery technique. Parathyroid hormone decreased (p < 0.001) and both vitamin D (p < 0.001) and C-terminal telopeptide of type I collagen (p = 0.001) increased after surgery. CONCLUSION: We demonstrated that calcium and phosphorous metabolism shows slight modification even after several years since metabolic surgery, irrespective of calcium and vitamin D supplementation. This different set point is characterized by a phosphate serum levels increase, together with a persistent bone loss, suggesting that supplementation alone may not ensure the maintenance of bone health in these patients.

GPU-accelerated Monte Carlo simulation of electron and photon interactions for radiotherapy applications.

Objective. The Monte Carlo simulation software is a valuable tool in radiation therapy, in particular to achieve the needed accuracy in the dose evaluation for the treatment plans optimisation. The current challenge in this field is the time reduction to open the way to many clinical applications for which the computational time is an issue. In this manuscript we present an innovative GPU-accelerated Monte Carlo software for dose valuation in electron and photon based radiotherapy, developed as an update of the FRED (Fast paRticle thErapy Dose evaluator) software.Approach. The code transports particles through a 3D voxel grid, while scoring their energy deposition along their trajectory. The models of electromagnetic interactions in the energy region between 1 MeV-1 GeV available in literature have been implemented to efficiently run on GPUs, allowing to combine a fast tracking while keeping high accuracy in dose assessment. The FRED software has been bench-marked against state-of-art full MC (FLUKA, GEANT4) in the realm of two different radiotherapy applications: Intra-Operative Radio Therapy and Very High Electron Energy radiotherapy applications.Results. The single pencil beam dose-depth profiles in water as well as the dose map computed on non-homogeneous phantom agree with full-MCs at 2% level, observing a gain in processing time from 200 to 5000.Significance. Such performance allows for computing a plan with electron beams in few minutes with an accuracy of ∼%, demonstrating the FRED potential to be adopted for fast plan re-calculation in photon or electron radiotherapy applications.

Progress in Development of Magadiite to Produce Multifunctional Lamellar Materials.

The attractive properties of magadiite, a lamellar and crystalline material, could give rise to new industrial processes due to its unique and modulating intrinsic properties. In this context, the high degree of expansion of its lamellae, a key factor for its potential use in several areas of scientific research, has attracted the attention of several researchers. The aim of this review is to provide a historical overview of the hypothetical models developed to explain the magadiite crystalline structure. Furthermore, different synthesis strategies for the preparation of magadiites as sodic, protonic, and hybrid (inorganic-inorganic and inorganic-organic) materials are discussed along with several routes for obtaining modified magadiites. Also, the use of magadiite in catalytic reactions, notably in ethanol dehydration and fructose conversion reactions, is a growing area of research. Other potential applications include the adsorption and absorption of environmental pollutants (e.g., phenol and methylene blue in wastewater), use as a photocatalyst in the oxidation of toluene, and use in medicine (e.g., as a drug delivery or antibacterial/antifungal agent). This highlights the many opportunities for the development of new synthesis methods to obtain multifunctional materials in the search for new applications.

Changes in quality of life after thyroidectomy in subjects with thyroid cancer in relation to the dose of levothyroxine.

PURPOSE: Previous studies demonstrated decreased quality of life (QoL) in differentiated thyroid cancer (DTC) survivors and suggested QoL variability related to time from thyroidectomy and levothyroxine dosage. The aims of this study were to evaluate QoL in thyroidectomized subjects in different levothyroxine states and to evaluate the association between TSH and thyroid hormones and QoL. METHODS: Prospective 5-year study enrolling 208 patients thyroidectomized for DTC, studied in one to four times according to levothyroxine dosage: withdrawal (WITHD), complete (C-SUPP) and mild TSH-suppression (M-SUPP), replacement (REPL). Each patient was allowed to participate into the study more than one time. A total of 300 evaluations were collected, consisting of detailed thyroid hormone profile and QoL assessment through the ThyPRO questionnaire. RESULTS: Comparing the four groups, significant differences were found for anxiety, impaired social and daily life and item 12 (overall impact of thyroid disease) domains (p < 0.05). Interestingly, C-SUPP subjects reported the best scores in almost all ThyPRO scales. Significant correlations were found between QoL and pituitary-thyroid axis function, as well as between QoL and gender, being females more affected. At multiple regression analyses fT3 demonstrated to be the best explanatory factor for overall impact of thyroid disease on the patient's life, followed by gender. CONCLUSIONS: TSH-suppressive doses of levothyroxine are more effective in improving QoL in DTC patients after thyroidectomy. These results confirm the urgent need of further studies aimed to define the best treatment of hypothyroidism, effective on well-being and harmless for patients.

Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up.

BACKGROUND: The single breath nitrogen (SBN2) test was proposed for early detection of "small airways disease" in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AIM: This study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. STUDY DESIGN AND METHODS: In this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. RESULTS: Among SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). CONCLUSION: In this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the "small airways disease" in the natural history of COPD.

The amino acid profile of Camelina sativa seeds correlates with the strongest immune response in dairy ewes.

Camelina sativa is an alternative protein source (with a specific amino acid profile) rich also in bioactive compounds (such as polyunsaturated fatty acids and antioxidants), which have immunomodulatory properties. This study aimed to assess the impact of the dietary inclusion level of Camelina seeds, on the expression levels of key genes involved in ewes' innate immunity. Forty-eight dairy ewes were assigned into four homogenous groups of 12 animals that were fed individually with alfalfa hay, wheat straw, and concentrate. The concentrate of the control group (CON) had no Camelina seeds, while in the treated groups, Camelina seeds (CSs) were incorporated at 6 (CS6), 11 (CS11), and 16% (CS16) in the concentrates, respectively, as partial substitution of both soybean meal and maize grain. The relative transcript levels of the immune-related genes were determined using a real-time PCR platform. The relative transcript levels of toll-interleukin receptor-domain-containing adapter-inducing interferon-ß, tumour necrosis factor receptor-associated factor 3, Interferon regulatory factor 5, and Mitogen-activated protein kinase were upregulated in monocytes of the CS11-fed ewes. Furthermore, in the CS6-fed ewes, the relative transcript levels of Interleukin-1 beta (IL1B) were upregulated in monocytes compared to the CON, while those of IL1B, Interleukin-8, and Interleukin-10 were upregulated in neutrophils compared to the CON and the CS11-fed ewes. The highest inclusion level of CS (CS16) did not have a negative impact on ewes' innate immunity. The response of monocytes on dietary amino acid (mainly threonine, tyrosine, serine, and lysine) changes related to Camelina inclusion is different from that of neutrophils. The observed responses need to be further investigated.

COVID-19 lockdown negatively impacted on adherence to denosumab therapy: incidence of non-traumatic fractures and role of telemedicine.

PURPOSE: Coronavirus disease (COVID-19) lockdowns have impacted on management of osteoporosis and the use of telemedicine is increasingly widespread albeit supported by little evidence so far. The aim of the study is to assess adherence to denosumab and incidence of non-traumatic fractures during the lockdown compared to the pre-COVID-19 year and to explore the effectiveness of telemedicine in the management of osteoporotic patients. METHODS: Retrospective, longitudinal, single-center study on patients receiving subcutaneous denosumab therapy every 6 months. Each patient was scheduled to undergo 2 visits: one during the pre-COVID-19 period (March 2019-March 2020) and another visit during the lockdown period (March 2020-March 2021). Data on new fractures, adherence, risk factors for osteoporosis and the modality of visit (telemedicine or face-to-face) were collected. RESULTS: The prevalence of non-adherent patients was higher during the lockdown (35 of 269 patients, 13.0%) than the pre-COVID-19 period (9 of 276 patients, 3.3%) (p < 0.0001). During the lockdown, the number of new non-traumatic fractures was higher than the pre-COVID-19 year (p < 0.0001): 10 patients out of 269 (3.7%) experienced a fragility fracture and 2 patients (0.7%) a probable rebound fracture during the lockdown period, whereas no patient had fragility/rebound fractures during the pre-COVID-19 period. No difference was found in the prevalence of non-adherence and new non-traumatic fractures comparing patients evaluated with tele-medicine to those evaluated with face-to-face visit. CONCLUSION: Non-adherent patients and new non-traumatic fractures (including rebound fractures) were more prevalent during the lockdown in comparison to the pre-COVID-19 period, regardless of the modality of medical evaluation.

Detailed comparison between organic and conventional milk from Holstein-Friesian dairy herds in Italy.

Several studies have reported gross composition differences between organic and conventional milk; however, most studies have not considered other factors such as breed and diet ingredients, which are known to influence milk composition. Thus, this study aimed to provide a detailed characterization of Holstein-Friesian cow milk from organic (ORG) and conventional (CONV) herds with similar diet ingredients and in the same geographic area. Bulk milk samples (n = 225) of 12 ORG and 12 CONV farms were collected from September 2019 to August 2020. Farms were located in Northern Italy, included corn (meal, silage, or both) in the lactating diets, and had similar management conditions, but ORG herds spent a period on pasture. Factors affecting milk composition were tested using a linear mixed model, which included calendar month, farming system (ORG and CONV), and their interactions as fixed effects, and farm nested within farming system as random effect. Results showed that total fat, lactose, vitamin E, and AA did not significantly differ between farming systems. Total protein and casein contents were significantly lower in ORG than CONV herds, and somatic cell score (SCS) was greater in ORG than CONV. Among minerals, differences were observed for Fe, K, Mg, and S in some months, being lower in ORG than CONV for K, Mg, and S and greater or lower for Fe depending on the month. Among fatty acid (FA) groups, index, and ratios, only polyunsaturated FA and n-3 FA tended to be greater in ORG than CONV, and cis-FA were greater in ORG than CONV during October. Among the most abundant individual FA, only C16:1n-9 differed, being lower in ORG than CONV. The calendar month (and hence seasonal feed ration) was significant for milk gross composition, SCS, vitamin E, mineral profile (except for Mo, Sr, and Zn), AA profile, FA groups (except for medium-chain FA), FA index and ratios, and individual FA (except C16:0). We conclude that the overall milk composition was quite similar between the 2 farming systems. This could be related to the similarity of the selected farms, the Holstein-Friesian breed, and generally high level of intensity in both farming systems.

Management of male factor infertility: position statement from the Italian Society of Andrology and Sexual Medicine (SIAMS) : Endorsing Organization: Italian Society of Embryology, Reproduction, and Research (SIERR).

PURPOSE: Infertility affects 15-20% of couples and male factors are present in about half of the cases. For many aspects related to the diagnostic and therapeutic approach of male factor infertility, there is no general consensus, and the clinical approach is not uniform. METHODS: In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), endorsed by the Italian Society of Embryology, Reproduction, and Research (SIERR), we propose evidence-based recommendations for the diagnosis, treatment, and management of male factor infertility to improve patient and couple care. RESULTS: Components of the initial evaluation should include at minimum medical history, physical examination, and semen analysis. Semen microbiological examination, endocrine assessment, and imaging are suggested in most men and recommended when specific risk factors for infertility exist or first-step analyses showed abnormalities. Full examination including genetic tests, testicular cytology/histology, or additional tests on sperm is clinically oriented and based on the results of previous investigations. For treatment purposes, the identification of the specific cause and the pathogenetic mechanism is advisable. At least, distinguishing pre-testicular, testicular, and post-testicular forms is essential. Treatment should be couple-oriented, including lifestyle modifications, etiologic therapies, empirical treatments, and ART on the basis of best evidence and with a gradual approach. CONCLUSION: These Guidelines are based on two principal aspects: they are couple-oriented and place high value in assessing, preventing, and treating risk factors for infertility. These Guidelines also highlighted that male infertility and in particular testicular function might be a mirror of general health of a man.

Benzodiazepines: Drugs with Chemical Skeletons Suitable for the Preparation of Metallacycles with Potential Pharmacological Activity.

The synthesis of organometallic compounds with potential pharmacological activity has attracted the attention of many research groups, aiming to take advantage of aspects that the presence of the metal-carbon bond can bring to the design of new pharmaceutical drugs. In this context, we have gathered studies reported in the literature in which psychoactive benzodiazepine drugs were used as ligands in the preparation of organometallic and metal complexes and provide details on some of their biological effects. We also highlight that most commonly known benzodiazepine-based drugs display molecular features that allow the preparation of metallacycles via C-H activation. These organometallic compounds merit further attention regarding their potential biological effects, not only in terms of psychoactive drugs but also in the search for drug replacements, for example, for cancer treatments.

Reduced FSH and LH action: implications for medically assisted reproduction.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play complementary roles in follicle development and ovulation via a complex interaction in the hypothalamus, anterior pituitary gland, reproductive organs, and oocytes. Impairment of the production or action of gonadotropins causes relative or absolute LH and FSH deficiency that compromises gametogenesis and gonadal steroid production, thereby reducing fertility. In women, LH and FSH deficiency is a spectrum of conditions with different functional or organic causes that are characterized by low or normal gonadotropin levels and low oestradiol levels. While the causes and effects of reduced LH and FSH production are very well known, the notion of reduced action has received less attention by researchers. Recent evidence shows that molecular characteristics, signalling as well as ageing, and some polymorphisms negatively affect gonadotropin action. These findings have important clinical implications, in particular for medically assisted reproduction in which diminished action determined by the afore-mentioned factors, combined with reduced endogenous gonadotropin production caused by GnRH analogue protocols, may lead to resistance to gonadotropins and, thus, to an unexpected hypo-response to ovarian stimulation. Indeed, the importance of LH and FSH action has been highlighted by the International Committee for Monitoring Assisted Reproduction Technologies (ICMART) in their definition of hypogonadotropic hypogonadism as gonadal failure associated with reduced gametogenesis and gonadal steroid production due to reduced gonadotropin production or action. The aim of this review is to provide an overview of determinants of reduced FSH and LH action that are associated with a reduced response to ovarian stimulation.

[Prolonged and post-term pregnancies: a regional survey of French clinical practices]. / Évaluation des pratiques professionnelles pour le suivi des grossesses prolongées dans un réseau de périnatalité.

OBJECTIVE: To assess professional practices of prolonged and post-term pregnancies in accordance to French guidelines. The secondary outcome was to evaluate neonatal and maternal morbidity during prolonged pregnancy. METHODS: Descriptive retrospective study was conducted in the 23 maternity hospitals of perinatal network between September and December 2018. The inclusion criterion was a birth term of≥41+0 weeks of gestation. Primary outcome was conformity to the national guidelines based on 10 items (conformity score≥80%). The secondary outcome was a composite criteria of neonatal morbidity (ventilation, resuscitation and/or Apgar score<7 at 5minutes) and maternal morbidity (obstetrical anal sphincter injury and/or postpartum hemorrhage). RESULTS: A total of 596 patients were included and the conformity was obtained in 65.3% of cases. Inconsistent criteria were amniotic fluid evaluation by the deepest vertical pocket (46.8%, n=279), and information of patients on prolonged pregnancy management (14.8%, n=88). Adverse perinatal outcome occurred for 40 newborns (6.0%) with shoulder dystocia (OR=5.2; CI 95%: 1.4-19.7) as a principal risk factor. Maternal morbidity outcome occurred in 70 cases (10.6%) primarily with increase in labour duration (OR=1.1 by hour of labour; CI 95%: 1.02-1.24) and prior caesarian section (OR=4.4; CI 95%: 1.8-11.0). CONCLUSIONS: Management of prolonged and post-term pregnancies matching with the French national guidelines. Points of improvement are amniotic fluid evaluation at term by a single deepest vertical pocket, and the information about induction of labour at term.

Inter-fractional monitoring of [Formula: see text]C ions treatments: results from a clinical trial at the CNAO facility.

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study.

Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role.

The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2-/-), ficolin-A (Fcna-/-), CL-11 (Colec11-/-), MASP-1/3 (Masp1-/-), MBL-C (Mbl2-/-), MBL-A (Mbl1-/-) or MBL-/- (Mbl1-/-/Mbl2-/-) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2-/-, MBL-/- and FCN-A-/- mice had better outcome scores compared to WT. Of these, MASP-2-/- mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2-/- mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.