Summary
Since sperm require high energy levels to perform their specialised function, it is vital that essential nutrients are available for spermatozoa when they develop, capacitate and acquire ...motility. However, they are vulnerable to a lack of energy and excess amounts of reactive oxygen species, which can impair sperm function, lead to immotility, acrosomal reaction impairment, DNA fragmentation and cell death. This monocentric, randomised, double‐blind, placebo‐controlled trial investigated the effect of 6 months of supplementation with l‐carnitine, acetyl‐l‐carnitine and other micronutrients on sperm quality in 104 subjects with oligo‐ and/or astheno‐ and/or teratozoospermia with or without varicocele. In 94 patients who completed the study, sperm concentration was significantly increased in supplemented patients compared to the placebo (p = .0186). Total sperm count also increased significantly (p = .0117) in the supplemented group as compared to the placebo group. Both, progressive and total motility were higher in supplemented patients (p = .0088 and p = .0120, respectively). Although pregnancy rate was not an endpoint of the study, of the 12 pregnancies that occurred during the follow‐up, 10 were reported in the supplementation group. In general, all these changes were more evident in varicocele patients. In conclusion, supplementation with metabolic and antioxidant compounds could be efficacious when included in strategies to improve fertility.
The 2-pentadecyl-2-oxazoline (PEA-OXA) is a natural compound with protective action in neuro-inflammation. We have previously shown that PEA-OXA behaves as an α2 adrenergic receptor (α2AR) antagonist ...and a putative protean agonist on histamine H3 receptors. Recently, neuroinflammation and monoaminergic neurotransmission dysfunction has drawn particular attention in Alzheimer Disease (AD) pathophysiology. In this context, the objective of this study was to investigate the effects of the dual-acting PEA-OXA in an AD-like model in mice. A combined computational and experimental approach was used to evaluate the ability of PEA-OXA to bind α2A-AR subtype, and to investigate the effects of PEA-OXA treatment on neuropathological (behavioural and functional) effects induced by soluble Amyloid β 1–42 (sAβ1–42) intracerebroventricular injection. Computational analysis revealed the PEA-OXA ability to bind the α2A-AR, a pharmacological target for AD, in two alternative poses, one overlapping the Na+ binding site. In vivo studies indicated that chronic treatment with PEA-OXA (10 mg/kg, os) restored the cognitive (discriminative and spatial memory) deficits and social impairments induced by sAβ injection. Consistently, electrophysiological analysis showed a recovery of the long-term potentiation in the hippocampus (Lateral Entorhinal Cortex-Dentate Gyrus pathway), while neuroinflammation, i.e., increased pro-inflammatory cytokines levels and microglia cells density were reduced. These data provide the basis for further investigation of the pro-cognitive aptitude of PEA-OXA by proposing it as an adjuvant in the treatment in AD, for which the available pharmacological approaches remain unsatisfactory. Moreover, this study offers new future direction in research investigating the role of α2AR in neuropsychiatric illness and therapies.
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•PEA-OXA reduces cognitive deficits mediated by Amyloid-β(1−42) intracerebroventricular injection.•PEA-OXA prevents impaired hippocampal synaptic plasticity and neuroinflammation associated with Amyloid-β(1−42).•PEA-OXA may act as a negative allosteric modulator of α2A adrenergic receptor.
The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non‐epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the ...treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients’ representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age‐related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive‐behavioural therapy as a first‐line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non‐epileptic seizure management should be multidisciplinary. High‐quality long‐term studies are needed to standardize PNES management.
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Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease ...so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC).
Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration.
CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P<0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category.
The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.
Recent developments of the nuclear emulsion technology led to the production of films with nanometric silver halide grains suitable to track low energy nuclear recoils with submicrometric length. ...This improvement opens the way to a directional Dark Matter detection, thus providing an innovative and complementary approach to the on-going WIMP searches. An important background source for these searches is represented by neutron-induced nuclear recoils that can mimic the WIMP signal. In this paper we provide an estimation of the contribution to this background from the intrinsic radioactive contamination of nuclear emulsions. We also report the neutron-induced background as a function of the read-out threshold, by using a GEANT4 simulation of the nuclear emulsion, showing that it amounts to about 0.06 per year per kilogram, fully compatible with the design of a 10 kg × year exposure.
The effect of angular misalignment on the low-frequency dynamics of the near wake of a blunt-based axisymmetric body is investigated at a Reynolds number of
$Re=67\,000$
. While for axisymmetric ...boundary conditions all azimuthal orientations of the wake are explored with equal probability, resulting in a statistical axisymmetry, an angular offset as small as
$0.2^{\circ }$
is found to suppress the low-frequency large-scale behaviour that is associated with the erratic meandering of the region of reversed flow. As a result of the misalignment, the centroid of this backflow region is displaced from the model axis and remains confined around an average off-centre position. Spectral and modal analysis provides evidence that the erratic backflow behaviour occurs within a narrow angular range of deviations from axisymmetric conditions.
Erectile dysfunction (ED), the second most common male sexual disorder, has an important impact on man sexuality and quality of life affecting also female partner's sexual life. ED is usually related ...to cardiovascular disease or is an iatrogenic cause of pelvic surgery. Many non-surgical treatments have been developed with results that are controversial, while surgical treatment has reached high levels of satisfaction. The aim is to evaluate outcomes and complications related to prosthesis implant in patients suffering from ED not responding to conventional medical therapy or reporting side effects with such a therapy. One hundred eighty Caucasian male suffering from ED were selected. The patient population were divided into two groups: 84 patients with diabetes and metabolic syndrome (group A) and 96 patients with dysfunction following laparoscopic radical prostatectomy for prostate cancer (group B). All subjects underwent primary inflatable penile prosthesis implant with an infrapubic minimally invasive approach. During 12 months of follow-up, we reported 3 (1.67%) explants for infection, 1 (0.56%) urethral erosion, 1 (0.56%) prosthesis extrusion while no intraoperative complications were reported. Mean International Index of Erectile Function-5 (IIEF-5) was 8.2 ± 4.0 and after the surgery (12 months later) was 20.6 ± 2.7. The improvement after the implant is significant in both groups without a statistically significant difference between the two groups (P-value 0.65). Mean Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score 1 year after the implant is 72.2 ± 20.7, and there was no statistically significant difference between groups A and B (P-value 0.55). Implantation of an inflatable prosthesis, for treatment of ED, is a safe and efficacious approach; and the patient and partner satisfaction is very high. Surgical technique should be minimally invasive and latest technology equipment should be implanted in order to decrease after surgery common complications (infection and mechanical failure).
Coeliac disease (CD) is a permanent inflammatory disease of the small intestine characterized by the destruction of the mucous membrane of this intestinal tract. Coeliac disease represents the most ...frequent food intolerance and affects about 1% of the population, but it is severely underdiagnosed. Currently available guidelines require CD-specific serology and atrophic histology in duodenal biopsy samples to diagnose CD in adults. In paediatric CD, but recently in adults also, non-invasive diagnostic strategies have become increasingly popular. In order to increase the rates of correct diagnosis of the disease without the use of biopsy, researchers have recently been using approaches based on artificial intelligence techniques. In this work, we present a Clinical Decision Support System (CDSS)system for supporting CD diagnosis, developed in the context of the Italy-Malta cross-border project ITAMA. The implemented CDSS has been based on a neural-network-based fuzzy classifier. The system was developed and tested using a Virtual Database and a Real Database acquired during the ITAMA project. Analysis on 10,000 virtual patients shows that the system achieved an accuracy of 99% and a sensitivity of 99%. On 19,415 real patients, of which 109 with a confirmed diagnosis of coeliac disease, the system achieved 99.6% accuracy, 85.7% sensitivity, 99.6% specificity and 96% precision. Such results show that the developed system can be used effectively to support the diagnosis of the CD by reducing the appeal to invasive techniques such as biopsy.
Osteochondroma, the most common benign bone tumor, may occur as a sporadic lesion or as multiple neoplasms in the context of multiple osteochondromas syndrome. The most severe complication is ...malignant transformation into peripheral secondary chondrosarcoma. Although both benign conditions have been linked to defects in EXT1 or EXT2 genes, contradictory reports are present in the literature regarding the requirement of their biallelic inactivation for osteochondroma development. A major limitation of these studies is represented by the small number of samples available for the screening. Taking advantage of a large series of tissues, our aim was to contribute to the definition of a genetic model for osteochondromas onset and transformation. EXT genes point mutations and big deletions were analyzed in 64 tissue samples. A double hit was found in 5 out of 35 hereditary cases, 6 out of 16 chondrosarcomas and 2 recurrences; none of the 11 sporadic osteochondromas showed two somatic mutations. Our results clearly indicate that, in most cases, biallelic inactivation of EXT genes does not account for osteochondromas formation; this mechanism should be regarded as a common feature for hereditary osteochondromas transformation and as an event that occurs later in tumor progression of solitary cases. These findings suggest that mechanisms alternative to EXT genetic alteration likely have a role in osteochondromas pathogenesis.
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