Search

BACKGROUND Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. AIM This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. METHODS [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. RESULTS Dexamethasone significantly inhibited T3 uptake at 10 μM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000 μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50 μM and 68% at 100 μM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10 μM. L-Carnitine inhibited T3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. CONCLUSION This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Purpose To assess the distribution of clinical features and metabolic abnormalities of polycystic ovary syndrome (PCOS) women according to their age. Methods Retrospective study on 602 women (mean age 23.9 ± 6.2 years), diagnosed according to International PCOS Network Guidelines criteria as having PCOS in a University-based Hospital. Anthropometric features, hormonal and metabolic parameters were measured and compared between the different age groups (group A ≤ 20 years; group B 21–30 years; group C > 30 years). Results Patients in group A were more often hyperandrogenic, while in group C hypertension, dyslipidemia, obesity, impaired fasting glucose, and insulin resistance (IR) were more prevalent. After adjusting for BMI, age correlated positively with sex hormone-binding globulin (SHBG), IR, total- and LDL-cholesterol, and negatively with DHEAS, insulin, and free androgen index (FAI). SHBG was significantly associated with IR and atherogenic dyslipidemia, while FAI levels were linked to hypertension, independently of other factors considered. Furthermore, the regression analysis showed a stronger relationship between BMI and metabolic outcomes, regardless of age. Conclusion Polycystic ovarian syndrome (PCOS) phenotype changes with age. Clinical and biochemical hyperandrogenism are a major concern in young PCOS women, while metabolic burden tends to increase with aging. Some of the cardiovascular risk factors are dependent on FAI and SHBG levels, whereas BMI confirms its key role in the genesis of most of the metabolic sequelae in PCOS, independently of age.

Recent studies have suggested that Mediterranean indigenous fish species are affected by bioactive metabolites coming from marine invasive species via food web interactions. In particular, both physiological and behavioural changes in the white sea bream Diplodus sargus were related to caulerpin (CAU), a bisindolic alkaloid particularly abundant in the invasive alga Caulerpa cylindracea, on which the fish actively feed. Dietary administration of CAU decreased aggressiveness in D. sargus, suggesting an anxiolytic-like effect of CAU possibly mediated by endogenous anxiolytic agents. This hypothesis is supported here by the finding of a significant increase of NPY transcriptional expression in the brain of fish fed with CAU enriched food, shedding more light on the neural mechanisms behind the altered behaviour of D. sargus. Fundação para a Ciência e a Tecnologia - FCT; FEDER info:eu-repo/semantics/publishedVersion

Enhanced recovery after surgery (ERAS) programs influence morbidity rates and length of stay after colorectal surgery (CRS), and may also impact major complications and anastomotic leakage rates. A prospective multicenter observational study to investigate the interactions between ERAS program adherence and early outcomes after elective CRS was carried out. Prospective enrolment of patients submitted to elective CRS with anastomosis in 18 months. Adherence to 21 items of ERAS program was measured upon explicit criteria in every case. After univariate analysis, independent predictors of primary endpoints [major morbidity (MM) and anastomotic leakage (AL) rates] were identified through logistic regression analyses including all significant variables, presenting odds ratios (OR). Institutional ERAS protocol was declared by 27 out of 38 (71.0%) participating centers. Median overall adherence to ERAS program items was 71.4%. Among 3830 patients included in the study, MM and AL rates were 4.7% and 4.2%, respectively. MM rates were independently influenced by intra- and/or postoperative blood transfusions (OR 7.79, 95% CI 5.46–11.10; p

Microorganism resistance to conventional antibiotics represents one of the major global health concerns. This paper focuses on a peptide (OctoPartenopin) extracted from suckers of Octopus vulgaris, bioassay-guided chromatographic fractionation was used to identify this sequence, which holds significant antibacterial activity against Gram-positive and Gram-negative bacteria. OctoPartenopin is encrypted within the calponin sequence and was associated with the high levels of proteolytic activity already reported in octopus arm suckers. We synthesized the parent peptide and four analogues, all peptide were tested for their antibacterial and antibiofilm activities. Preliminary antibiofilm experiments showed that that one of the analogues had the best activity in both inhibition and eradication of biofilm of all three microorganisms tested. The occurrence of OctoPartenopin in arm suckers provided novel speculative information on animal behavior, as concerns maternal care of fertilized eggs. Our results highlight that suckers are a rich source of multifaceted peptides to develop alternative antimicrobial agents and food preservatives.

Octopuses are unique invertebrates, with sophisticated and flexible behaviors controlled by a high degree of brain plasticity, learning, and memory. Moreover, in Octopus vulgaris, it has been demonstrated that animals housed in an enriched environment show adult neurogenesis in specific brain areas. Firstly, we evaluated the optimal acclimatization period needed for an O. vulgaris before starting a cognitive stimulation experiment. Subsequently, we analyzed differential gene expression in specific brain areas in adult animals kept in tested (enriched environment), wild (naturally enriched environment), and control conditions (unenriched environment). We selected and sequenced three protocadherin genes (PCDHs) involved in the development and maintenance of the nervous system, three Pax genes that control cell specification and tissue differentiation, the Elav gene, an earliest marker for neural cells, and the Zic1 gene, involved in early neural formation in the brain. In this paper, we evaluated gene expression levels in O. vulgaris under different cognitive stimulations. Our data shows that Oct-PCDHs genes are upregulated in the learning and lower motor centers in the brain of both tested and wild animals (higher in the latter). Combining these results with our previous studies on O. vulgaris neurogenesis, we proposed that PCDH genes may be involved in adult neurogenesis processes, and related with their cognitive abilities.

Introduction: Nephron-sparing surgery (NSS) is of one of the most studied fields in urology due to the balancing between renal function preservation and oncological safety of the procedure. Aim of this short review is to report the state of the art of intra-operative ultrasound as an operative tool to improve localization of small renal masses partially or completely endophytic during robotassisted partial nephrectomy (RAPN). Material and methods: We performed a literature review by electronic database on Pubmed about the use of intra-operative US in RAPN to evaluate the usefulness and the feasibility of this procedure. Results: Several studies analyzed the use of different US probes during RAPN. Among them some focused on using contrastenhanced ultra sonography (CEUS) for improving the dynamic evaluation of microvascular structure allowing the reduction of ischemia time (IT). We reported that nowaday the use of intraoperative US during RAPN could be helpful to improve the preservation of renal tissue without compromising oncological safety. Moreover, during RAPN there is no need for assistant to hand the US probe increasing surgeon autonomy. Conclusions: The use of a robotic ultrasound probe during partial nephrectomy allows the surgeon to optimize tumor identification with maximal autonomy, and to benefit from the precision and articulation of the robotic instrument during this key step of the partial nephrectomy procedure. Moreover US could be useful to reduce ischemia time (IT). The advantages of nephron-sparing surgery over radical nephrectomy is well established with a pool of data providing strong evidence of oncological and survival equivalency. With the progressive growth of robot-assisted partial nephrectomy (RAPN) techniques, the use of several tools has been progressively developed to help the surgeon in the identification of masses and its vascular net. In this short review we tried to analyze the current use of intra-operative ultrasound as an operative tool to improve localization of small renal masses partially or completely endophytic during RAPN.

Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. To investigate whether some common drugs can inhibit MCT8-mediated T3 transport, [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of drugs. The mode of inhibition was also determined. Dexamethasone inhibited T3 uptake at 10 μM; hydrocortisone reduced T3 uptake at 500 and 1000 μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50 μM and 68% at 100 μM), this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake even at low concentrations. L-carnitine inhibited T3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, dronedarone behave as potent inhibitors of MCT8.

Functional connectivity (FC) of brain networks dynamically fluctuates during both rest and task execution. Individual differences in dynamic FC have been associated with several cognitive and behavioral traits. However, whether dynamic FC also contributes to sensorimotor representations guiding body-environment interactions, such as the representation of peripersonal space (PPS), is currently unknown. PPS is the space immediately surrounding the body and acts as a multisensory interface between the individual and the environment. We used an audio-tactile task with approaching sounds to map the individual PPS extension, and fMRI to estimate the background FC. Specifically, we analyzed FC values for each stimulus type (near and far space) and its across-trial variability. FC was evaluated between task-relevant nodes of two fronto-parietal networks (the Dorsal Attention Network, DAN, and the Fronto-Parietal Network, FPN) and a key PPS region in the premotor cortex (PM). PM was significantly connected to specific task-relevant nodes of the DAN and the FPN during the audio-tactile task, and FC was stronger while processing near space, as compared to far space. At the individual level, less PPS extension was associated with stronger premotor-parietal FC during processing of near space, while the across-trial variability of premotor-parietal and premotor-frontal FC was higher during the processing of far space. Notably, only across-trial FC variability captured the near-far modulation of space processing. Our findings indicate that PM connectivity with task-relevant frontal and parietal regions and its dynamic changes participate in the mechanisms that enable PPS representation, in agreement with the idea that neural variability plays a crucial role in plastic and dynamic sensorimotor representations.

Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation inOctopus. However, little is known about the precise molecular circuitry of NPY-mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here we examined the expression of NPY throughout theOctopuscentral nervous system. The sequence analysis ofOctopusNPY precursor confirmed the presence of both signal peptide and putative active peptides, which are highly conserved across bilaterians.In situhybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY-dependent modulation inOctopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also verified the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of theOctopusfeeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in variousOctopusbehaviors.Research Highlights/Graphical Abstract textNeuropeptide Y (NPY), an evolutionarily conserved neurosecretory molecule, is expressed in specialized regions of theOctopusbrain controlling feeding, reproduction, and visual and tactile memory circuits. Extrasomatic mRNAs were found in neurites, suggesting synaptic synthesis of NPY.

Purpose: Transurethral resection of the bladder (TURB) is a common endoscopic procedure. Perioperative antimicrobial prophylaxis (AMP) is used to reduce the risk of infectious complications. However, there is an absence of knowledge about both incidence of infectious complications after TURB and advantage of AMP in general. The objective of this study is to determinate the prevalence of postoperative infectious complications after routine TURB without AMP. Methods: We retrospectively reviewed clinical data of all patients who underwent TURB in the same Academic Urologic Department between January 2011 and December 2013. We consider as relevant for analysis, patients that underwent TURB without receiving any AMP. Infection was defined as a body temperature >37.5°C sustained for at least 24 hours. Sepsis was defined according to the third international consensus definition for sepsis and septic shock. Results: In the period of the study, 223 TURBs were performed without use of AMP. Mean age was 70.3 years (standard deviation [SD] 11.3). Mean operative time was 25.14 minutes (SD 16). Median length of hospital stay was 3 days (interquartile range [IQR]: 2-4). Six (2.7%) patients developed postoperative infective complications. No case of sepsis was reported. Two (0.9%) patients received an antimicrobial therapy with fluoroquinolones despite absence of any signs of infection. Two hundred fifteen (96.4%) patients of TURBs did not receive any antimicrobial drugs and did not develop any infectious complications. Conclusion: In our series, infectious complications after TURB occurred in

Inappropriate processing and disposal of electronic waste contributes to the contamination of aquatic systems by various types of pollutants such as the rare-earth elements (REE) in which lanthanum (La) is included. Knowledge on the toxicity of these elements in marine organisms is still scarce when compared to other metals such as mercury (Hg) and arsenic (As). Therefore, this study aims to assess the toxicity of La on the mussel Mytilus galloprovincialis, considered a good bioindicator of aquatic pollution, through the analysis of metabolic, oxidative stress, neurotoxicity and histopathological markers. Organisms were exposed to different concentrations of La for a period of 28 days (0, 0.1, 1, 10 mg/L) under controlled temperature (18 °C ± 1.0) and salinity (30 ± 1) conditions. La concentrations in mussels increased in higher exposure concentrations. La exposure demonstrated a biochemical response in mussels, evidenced by lowered metabolism and accumulation of energy reserves, activation of the antioxidant defences SOD and GPx as well as the biotransformation enzymes GSTs, especially at intermediate concentrations. Despite oxidative stress being shown by a decrease in GSH/GSSG, oxidative damage was avoided as evidenced by lower LPO and PC levels. Inhibition of the enzyme AChE demonstrated the neurotoxicity of La in this species. Histopathological indices were significantly different from the control group, indicating impacts in gonads, gills and digestive glands of mussels due to La. These results show that La can be considered a risk for marine organisms and thus its discharge into the environment should be monitored.

The ecological theory of island biogeography suggests that mainland populations should be more genetically divergent from those on large and distant islands rather than from those on small and close islets. Some island populations do not evolve in a linear way, but the process of divergence occurs more rapidly because they undergo a series of phenotypic changes, jointly known as the Island Syndrome. A special case is Reversed Island Syndrome (RIS), in which populations show drastic phenotypic changes both in body shape, skin colouration, age of sexual maturity, aggressiveness, and food intake rates. The populations showing the RIS were observed on islets nearby mainland and recently raised, and for this they are useful models to study the occurrence of rapid evolutionary change. We investigated the timing and mode of evolution of lizard populations adapted through selection on small islets. For our analyses, we used an ad hoc model system of three populations: wild-type lizards from the mainland and insular lizards from a big island (Capri, Italy), both Podarcis siculus siculus not affected by the syndrome, and a lizard population from islet (Scopolo) undergoing the RIS (called P. s. coerulea because of their melanism). The split time of the big (Capri) and small (Scopolo) islands was determined using geological events, like sea-level rises. To infer molecular evolution, we compared five complete mitochondrial genomes for each population to reconstruct the phylogeography and estimate the divergence time between island and mainland lizards. We found a lower mitochondrial mutation rate in Scopolo lizards despite the phenotypic changes achieved in approximately 8,000 years. Furthermore, transcriptome analyses showed significant differential gene expression between islet and mainland lizard populations, suggesting the key role of plasticity in these unpredictable environments.

Background Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days. Results We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported. Conclusions After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668.)

Purpose To evaluate the risk of mass enlargement and endocrine function modification in patients with adrenal incidentaloma (AI). Methods In this retrospective study, we examined clinical and hormonal characteristics of 310 patients with AI (200 females and 110 males; age: 58.3 ± 12.9 years), followed up for a median (interquartile range) of 31.4 months (13.0–78.6) and evaluated for possible modification in adrenal mass size and hormonal function. The hormonal evaluation included morning serum cortisol and plasma ACTH at 8 a.m., aldosterone, plasma renin activity/direct renin concentration, and 24-h urine metanephrines/normetanephrines. One microgram overnight dexamethasone suppression test (DST) was performed. Autonomous cortisol secretion (ACS) was diagnosed in the presence of cortisol after 1 mg DST > 5 μg/dl (138 nmol/l) or >1.8 and ≤5 μg/dl (50–138 nmol/l) and at least one of the following: (i) low ACTH; (ii) increased 24-h urinary-free cortisol; (iii) absence of cortisol rhythm; and (iv) post-LDDST cortisol level > 1.8 μg/dl (50 nmol/l). When there was no biochemical evidence of adrenal hormonal hyperactivity, AIs were classified as nonfunctioning (NFAIs). The mass was considered significantly enlarged when the size increase was more than 20% and at least 5 mm compared to baseline. Results At diagnosis, NFAIs were found in 209 patients, while ACS and overt adrenal hyperfunction were diagnosed in 81 and 20 patients, respectively. During follow-up, 3.3% and 1.5% of patients with NFAI developed subtle and overt endocrine hyperfunction, respectively, while a significant mass enlargement was observed in 17.7% of all AIs. The risk of developing ACS was significantly higher in patients with adenoma >28 mm (hazard ratio [HR] 12.4; 95% confidence interval [CI], 2.33–66.52, P = 0.003), in those with bilateral adrenal tumors (HR: 5.36; 95% CI, 1.17–24.48, P = 0.030), and with low/suppressed ACTH values (HR: 11.2, 95% CI 2.06–60.77; P = 0.005). The risk of mass enlargement was lower for patients in the fourth quartile of body mass index than those in the first quartile (HR 0.33; 95% CI, 0.14–0.78; P = 0.012). Conclusions In patients with AI, the risk of developing hormonal hyperfunction and mass enlargement is overall low, although some tumor characteristics and anthropometric features might increase this risk. Taking account of all these aspects is important for planning a tailored follow-up in AI patients.

According to the dimensional approach to psychosis, there is a continuum from low schizotypy to schizophrenia patients. The temporal aspect of sensory processing seems to be compromised across such continuum, as suggested by different studies separately investigating unisensory or multisensory domains. Most of these studies have so far focused primarily on the temporal processing of visual and auditory stimuli, either in schizotypy or schizophrenia, while leaving the tactile domain and the integration of touch with other senses mostly unexplored. Given the relevance of body-related perceptual abnormalities for psychosis proneness, we aimed at filling this gap in the literature across two studies. We asked participants with increasing levels of schizotypy (study 1) and schizophrenia patients (study 2) to perform three simultaneity judgement tasks: a unimodal tactile task, a unimodal auditory task and a bimodal audio-tactile task. Each task allowed estimating a simultaneity range (SR), as a proxy of the individual tolerance to asynchronies in the tactile, auditory and audio-tactile domains, respectively. Results showed larger SRs as the level of schizotypy increases. Specifically, the linear effect of schizotypy levels on the audio-tactile task was stronger than on the auditory task, which in turn was greater than the effect on the tactile task (study 1). Differently, schizophrenia patients showed larger SRs than controls in all the three tasks (study 2). The current study is the first empirical investigation across the continuum from low schizotypy to schizophrenia of the tolerance to asynchronies in the processing of external (auditory) and body-related (tactile) inputs.

Spine surgery is nowadays performed for a great number of spine pathologies; it is estimated that 4.83 million surgeries are carried out globally each year. This prevalence led to an evolution of spine surgery into an extremely specialized field, so that traditional open interventions to the spine were integrated and often replaced by minimally invasive approaches. Despite the several benefits associated to robotic minimally invasive surgeries (RMIS), loss of depth perception, reduced field of view and consequent difficulty in intraoperative identification of relevant anatomical structures are still unsolved issues. For these reasons, Augmented Reality (AR) was introduced to support the surgeon in surgical applications. However, even though the irruption of AR has promised breakthrough changes in surgery, its adoption was slower than expected as there are still usability hurdles. The objective of this work is to introduce a client software with marker-based optical tracking capabilities, included into a client-server architecture that uses protocols to enable real-time streaming over the network, providing desktop rendering power to the head mounted display (HMD). Results relative to the tracking are promising (Specificity = 0.98 ± 0.03; Precision = 0.94 ± 0.04; Dice = 0.80 ± 0.07) as well as real-time communication, which was successfully set.

Introduction Pelvic-ureteric junction obstruction (PUJO) in a duplex system is an nusual entity that commonly involves the lower moiety [1] , [2] , [3] . The surgical management in such cases may be very challenging due to anatomical issues. We report our experience with robot assisted pyeloplasty in a case of partial duplex system with lower moiety PUJO. Materials and methods A 59-year old woman presented with a recurrent right flank pain of a 3 years duration. Ultrasonography showed hydronephrosis of the right kidney and CT scan revealed a right partial duplex system. A UPJO was confirmed as having originated from the extensive dilated lower moiety of the duplex system. MAG-3 renogram showed a 53% kidney function in the right kidney. We planned a robot assisted laparoscopic pyeloplasty previous to a Contour stent positioning according with the “window technique” [ 4 , 5 ]. Results Total operative time was 167 minutes with a total blood loss of about 20 cc. The post-operative course was uncomplicated and the patient was discharged on postoperative day four. The double J stent was removed six weeks after surgery. The post-operative MAG-3 renogram performed at 4-month from surgery did not show significant modification in terms of kidney function. Conclusions Robotic-assisted pyeloplasty for lower moiety UPJ obstruction in a partial duplex system is feasible, safe and effective. The experience of the surgical equipe and a good preoperative plan are the key to success.

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

The identification of local damages in structural elements is considered. In the proposed formulation, the damages are represented as local changes in structural stiffness and they are defined by a set of parameters. The main effort of this work is directed to the use of global measures of energy to indicate the local changes of stiffness. An idea of use of additional design parameters in order to optimize the experiment and to enlarge the sensitivity of objective functional with respect to damage parameters is applied. In order to accomplish this goal, the distribution of energy within the structural domain is optimized. Two cases, namely the eigenproblem and the structure under the static external load, are discussed. Simple illustrative example of identification of damage is discussed, and numerical results are presented.

In this paper, we propose a model for the description of bone mechanics and bone remodeling processes, including bone cell populations dynamics. The latter, described by a system of ODEs, influences the values for the elastic parameters used in the mechanical model, which in turn determines the “stimulus” function affecting the behavior of the cells. Numerical simulations concerning the behavior of the bone under external loads, as well as simple fracture healing processes are presented. The model can reproduce the qualitative behavior of bone tissue remodeling and mechanical response.

Introduction & Objectives: Non-muscle invasive urothelial bladder cancer (NMIBC) represents a common neoplasm in patients older than 75 years old. Our aim was to analyze retrospectively the population of patients (pts) older than 85 years old treated at our department for bladder tumor. Primary outcome measures were the evaluation of overall survival (OS) and recurrence related to clinical-pathological features. Secondary outcome measures were the evaluation of any relation between treatmeants and OS. Materials & Methods: We looked retrospectively at 118 patients aged 85 years old or more who underwent transurethral resection (TURBT) for bladder tumor (BT) in our hospital between 2001 and 2015. We registered pre-operative clinical-pathological features and clinical outcomes. Statistical analysis was performed by SPSS. Results: A total of 47 females (39.8%) and 71 males (60.2%) with an a mean age of 88.13 (SD +/- 3.17) and mean ASA score 2.55 (+/- 0.5) were included in this study; 91 pts died (77.1%) and 27 (22.9%) are alive. Median time-to-death was 13.5 months (IQR 2-34) and median disease free survival (DFS) was 8 months (IQR 0-24). At diagnosis 28 pts already had advanced disease (23.72%). 4 pts underwent radical cistectomy (RC), 2 had partial cistectomy, 1 had radiotherapy for palliation and 110 had no further radical treatments (93.22%). Histotype was urothelial in 99 pts (83.89%), squamoid in 9 patients (7.62%) and undifferentiated in 10 cases (8.47%). 92 pts had no intravescical therapy (77.96%); 19 had BCG (16.1%) and 7 had MMC (5.93%). 79 pts had low grade (LG) disease (66.94%), 38 had high grade (HG) disease (32.20%) and 1 patient had CIS (0.84%). Among pts with HG disease 7 survived (18.4%) and 31 died (81.6%); among those with LG disease 20 survived (25.3%) and 59 died (74.7%). Among pts who received an intravescical treatment 33.33% survived; among those who did not received it 19.57% survived. Total recurrence rate was 38.14%. Conclusions: Bladder cancer is a well-known disease with an high rate of morbidity and mortality. In our series, HG grade disease, was not associated with higher mortality rate (81.6% vs 74,7% p=0.157) nor with recurrence rate (p=0.452). Tumor size and histotype seemed to be related to recurrence (p=0.001 and p=0.009 respectively). Intravescical treatment did not seemed to improve OS (p=0.06). Men seemed to have higher risk of recurrence (47.8% vs 23.4%, p=0.006). In the whole population recurrence seemed to not affect overall survival (p=0.72). Our study seems to demonstrate that clinico-pathological features of BT does not affect OS in very elderly pts. Further studies in larger cohorts of pts maybe needed.

Octopus vulgaris is a unique model system for studying complex behaviors in animals. It has a large and centralized nervous system made up of lobes that are involved in controlling various sophisticated behaviors. As such, it may be considered as a model organism for untangling the neuronal mechanisms underlying behaviors—including learning and memory. However, despite considerable efforts, Octopus lags behind its other counterparts vis-à-vis its utility in deciphering the cellular, molecular and synaptic mechanisms underlying various behaviors. This study represents a novel approach designed to establish a neuronal cell culture protocol that makes this species amenable to further exploitation as a model system. Here we developed a protocol that enables dissociation of neurons from two specific Octopus' brain regions, the vertical-superior frontal system and the optic lobes, which are involved in memory, learning, sensory integration and adult neurogenesis. In particular, cells dissociated with enzyme papain and cultured on Poly-D-Lysine-coated dishes with L15-medium and fetal bovine serum yielded high neuronal survival, axon growth, and re-growth after injury. This model was also explored to define optimal culture conditions and to demonstrate the regenerative capabilities of adult Octopus neurons after axotomy. This study thus further underscores the importance of Octopus neurons as a model system for deciphering fundamental molecular and cellular mechanism of complex brain function and underlying behaviors.

Aim of the study: Evidences about utility of AMP in order to reduce infectious complications resulting from TURB are lacking. Objectives of this study are to determine the frequency of febrile infectious complications after TURB with and without AMP and to asses risk factors for postoperative infectious complications. Materials and methods: We retrospectively reviewed clinical data of all patients who underwent TURB in our institution between January 2011 and December 2016. Reviewing all clinical document produced during the in-stay periods we collected data about patient and tumor features. The end point was incidence of infections defined as a body temperature >37.5° sustained for at least 24h and elevation of serum inflammatory markers during postoperative stay. Results: In the period of the study a total of 829 consecutive TURBs were performed. 753 TURB/patients matched the inclusion criteria, 565 (75%) male and 188 women (25%). Median age was 72,5 years (IQR: 67–80). Median operative time was: 27.7 (IQR 15–35) minutes. Median Length of post-operative hospitalization was 3,23 days (IQR 2– 4). A total of 31 (4,16%) patients developed an infectious complication. 599 patients did not receive any AMP, 3,7% of patients in this group developed an infective complication. AMP was given to 154 patients and 7,14% of the patients in this group developed an infective complication. A significant correlation between use of AMP and incidence of infectious complications was found ( p:0,034). Preoperative urinocolture were negative for 664 (88,2%) patients, positive for 72 (9,5%) patients and not disposable for 17 (2,3%) patients. 7,5% of the patients with positive preoperative urinocolture developed an infectious complication versus the 3,6% of patients with negative urinocolture (p:0,0028). 158 patients presented BPH, 11 of them developed an infectious complication. BPH was correlated with higher risk of postoperative infectious ( p:0,0429). Discussion: To our knowledge this is the biggest series analyzing risk of infectious complications after TURB and the only study that provides a sub-group analysis according to presence of risk factors for post- operative infections. Given our result, the use of AMP before routine TURB seems to be unnecessary.

INTRODUZIONE E SCOPO: L'incremento di peso si osserva frequentemente nei pazienti sotto- posti a Trapianto di Fegato. Questa condizione e spesso associata allo sviluppo di altre compli- canze che potrebbero influenzare la sopravvivenza a lungo termine. Tuttavia, i fattori di rischio non sono stati ancora chiarificati. Lo scopo dello studio e di rilevare la prevalenza di sovrappeso e obesitaI€, e la variazione del BMI nei tre anni successivi al trapianto, e di identificare i fattori di rischio associati. METODO: Sono stati retrospettivamente reclutati i soggetti sottoposti a Trapianto di Fegato, presso la Fondazione IRCCS " CaI€ Granda – Ospedale Maggiore Policlinico" di Milano dal 1° Gennaio 2005 al 30 Giugno 2014.Sono stati reperiti parametri clinici, biochimici e farmaco- logici, alla dimissione e ad 1,2,3 anni dal trapianto di fegato. RISULTATI: Sono stati inclusi 145 soggetti, 95(66%) uomini, 53 anni (44-59), 48(33%) affetti da Cirrosi HBV+HDV correlata, 30(21%) da Cirrosi Etiltossica. Alla dimissione il BMI dei soggetti era 21.9 Kg/m2 e la prevalenza di sovrappeso era del 14%; gli stessi parametri dopo 1,2 e 3 anni di follow-up erano, rispettivamente, 25.6 Kg/m2 e 40%, 25.5 Kg/m2 e 41%, 25.4 Kg/m2 e 37%. L'incremento medio di peso corporeo, durane il primo anni, e stato di 9.8 Kg(p

Organisms showing a complex and centralized nervous system, such as teleosts, amphibians, reptiles, birds and mammals, and among invertebrates, crustaceans and insects, can adjust their behavior according to the environmental challenges. Proliferation, differentiation, migration, and axonal and dendritic development of newborn neurons take place in brain areas where structural plasticity, involved in learning, memory, and sensory stimuli integration, occurs. Octopus vulgaris has a complex and centralized nervous system, located between the eyes, with a hierarchical organization. It is considered the most "intelligent" invertebrate for its advanced cognitive capabilities, as learning and memory, and its sophisticated behaviors. The experimental data obtained by immunohistochemistry and western blot assay using proliferating cell nuclear antigen and poli (ADP-ribose) polymerase 1 as marker of cell proliferation and synaptogenesis, respectively, reviled cell proliferation in areas of brain involved in learning, memory, and sensory stimuli integration. Furthermore, we showed how enriched environmental conditions affect adult neurogenesis.

Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development. 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy–Weinberg equilibrium was performed. None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development. Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

Background: The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the ...

The peripersonal space (PPS) is a multisensory and sensorimotor interface between our body and the environment. The location of PPS boundary is not fixed. Rather, it adapts to the environmental context and differs greatly across individuals. Recent studies have started to unveil the neural correlates of individual differences in PPS extension; however, this picture is not clear yet. Here, we used approaching auditory stimuli and magnetoencephalography to capture the individual boundary of PPS and examine its neural underpinnings. In particular, building upon previous studies from our own group, we investigated the possible contribution of an intrinsic feature of the brain, that is the “resting state” functional connectivity, to the individual differences in PPS extension and the frequency specificity of this contribution. Specifically, we focused on the activity synchronized to the premotor cortex, where multisensory neurons encoding PPS have been described. Results showed that the stronger the connectivity between left premotor cortex (lPM) and a set of fronto-parietal, sensorimotor regions in the right and left hemisphere, the wider the extension of the PPS. Strikingly, such a correlation was observed only in the beta-frequency band. Overall, our results suggest that the individual extension of the PPS is coded in spatially- and spectrally-specific resting state functional links.

Aim of the Study: In male infertility, the current challenge is to properly reconcile new and old techniques taking into account costbenefit and scientific evidence for both. The aim of our work was to evaluate if microsurgical reconstruction of the seminal pathway in patients with proximal obstruction can still be considered an effective treatment for infertile men suffering from obstructive azoospermia in the light of new medically assisted procreation techniques. Materials and Methods: From 1995 to 2016, at the Urological Clinic of the University of Trieste and the University College London Hospital (UCLH), 242 patients with obstructive azoospermia underwent microsurgical treatment of recanalization of the seminal pathways. Among these patients, 161 patients underwent Vasoepididimostomy (EDV), 72 at vasovasostomy (VV) and 9 at VV + EDV. The average age was 41 (±7.9). Patients were subdivided according to the type of microsurgical reconstruction performed. Patients previously undergoing unsuccessful attempts at microsurgical reconstruction, patients with infertile or poorly motivated female partners to have a child and patients undergoing recanalization after retention pain vasectomy were excluded from the study. The primary objective of the study was to evaluate the rate of patency of the seminal pathways and the pregnancy rate. Results: In patients undergoing EDV and VV, the success rate in terms of patency of the anastomosis was 75% and 42%, respectively, while the pregnancy rate of 55% and 13%. The patency of the cumulative anastomosis was 48% (109/185) and the general pregnancy rate of 19% (30/161). In the 92 patients who underwent “vasectomy reversal” the mean time interval between vasectomy and microsurgical reconstruction (IT) was 12.2 years (SD: 12.2 ± 6.41; 1–27). In this category of patients the results were inversely proportional to the average time spent by vasectomy. Discussion: According to the literature, our results confirm that microsurgical reconstruction of the seminal pathways remains a valid therapeutic option with an excellent cost/benefit ratio in patients with obstructive azoospermia. The best results are in previously vasectomized patients and are inversely proportional to the time elapsed.

Aim of the Study: Penile cancer (PC) is an uncommon malignant tumor, with an overall incidence of around 1/100,000 males in Europe and the USA. The incidence of penile cancer increases with age, with a peak in the sixth decade but it does occur in younger men. The aims of the treatment of the primary tumour are complete tumour removal with as much organ preservation as possible, without compromising oncological control. Local treatment modalities for localised PC include excisional surgery, external beam radiotherapy (EBRT), brachytherapy and laser ablation. However, treatment choice depends on tumour size, histology, stage and grade, localisation (especially relative to the meatus) and patient preference. Glansectomy with distal corporectomy and reconstruction or partial amputation with reconstruction are recommended for disease invading the corpora cavernosa and/or urethra (T3). We report two cases of patients undergoing partial penectomy and total penectomy with perineal urrthrostomy. Year of production: 2018. Materials and Methods: The first patient (61 years) came to our attention with a hard, swelling and necrotic lesion involving the glans and the distal portion of the penis, in association with bilateral lymphadenopathy. Ulrtrasonographic and magnetic resonance investigations confirmed the invasion of the right corpus cavernosum. The patient underwent partial penectomy and bilateral lymphadenectomy. The second patient (75 years) presented with a big necrotic lesion involving the glans and the foreskin, that appeared fused together. Ultrasonographic and magnetic resonance imaging confirmed the invasion of the glans, with dubious involment of corpora cavernosa. Total penectomy, bilateral orchidectomy and perineal urethrostomy was performed, in association with fine needle aspiration cytology to the lymphnodes. Results: In the first case histopathological diagnosis was squamous cell carcinoma involving the glans, the corpus spongiosum and urethra. Marginal involving of the corpora cavernosa. Lymphnodes resulted free from desease. (TNM Classification: pG2.C2.T3.N0.Pn1). The histopathological diagnosis in the second case was squamous cell carcinoma with verrucoid aspects involving the glans and the corpus spongiosum, with corpora cavernosa and urethral margin free from desease (TNM Classification: pG2.C2.T2.R0.Nx). Discussion: As PC can be a morbid and disfiguring ailment, every effort must be made to preserve penile length and functionality, while attaining adequate cancer control. Although maximal penile preservation would be ideal, proper cancer control remains the primary goal of treatment and therefore must be pursued in the management plan for each individual patient with adapted techniques to minimize recurrence and improve functional outcomes.

INTRODUCTION AND OBJECTIVES: Increasing life expec- tancy in the general population and the fact that a disproportional burden of cancer occurs in people age ! 65 years old have generated great interest in delivering better cancer care for older adults. EORTC and NCCN recommend that all patients with cancer age ! 70 years old should undergo some form of geriatric assessment. G8 Screening Tool is a robust geriatric tool to identify a geriatric risk profile and for prediction of functional decline and prognostic information for overall survival. We evaluated the role of G8 Screening Tool in the assessment of outcome of elderly patients (! 70 y.o.) underwent surgery for kidney tumours. METHODS: We prospectively enrolled 162 patients (! 70 years old at surgery date) from January 2012 to January 2016 underwent surgery at two urological institution.G8 Screening Tool was applied to each patient before surgery. We divided population into two groups (frail group vs. not-frail group) in relation to the geriatric risk profile based on G8 score ( 14 vs. > 14 respectively). The aim was to identify the role of G8 Score in predicting intraoperative, postoperative complications and functional outcomes. RESULTS: A total of 70 females (34%) and 92 (46%) males were included in the analysis. 69 patients (42,6%) underwent PN, while 93 patients (57,4%) underwent RN. Mean age at surgery was 76.57 (SD6,37). Comorbidity factors were included: mean CCI was 3.06 (SD1,99) with CCI > 5 points in 18 patients (15,65%), mean BMI was 25,15 (SD2,87), 55 patients (34%) with DM, 98 patients (60%) with HTN. CKD stage III was present in 73 patients (45,1%) underwent sur- gery. Mean ECOG PS was 1,53 (SD0,66) with score ! 3 in 7 patients (6,1%). Mean ASA Score was 2,84 (SD0,73). According to the G8 Score, 91 patients (60%) were included in the frail group and 71 (40%) in the not-frail group. 41 patients of frail group vs. 2 patients of not-frail group developed intraoperative complications (p

Adult neurogenesis is widespread among metazoans, it occurs in animals with a network nervous system, as cnidarians, and in animals with a complex and centralized brain, such as mammals, non-mammalian vertebrates, ecdysozoans, and a lophotrochozoan, Octopus vulgaris. Nevertheless, there are important differences among taxa, especially in the number of the regions involved and in cell proliferation rate during the life-cycle. The comparative evaluation of adult neurogenesis among different brain regions is an arduous task to achieve with only stereological techniques. However, in Octopus vulgaris we recently confirmed the presence of active proliferation in the learning-memory centers, multisensory integration centers, and the motor centers of the adult brain. Here, using a flow cytometry technique, we provide a method to quantify the active proliferation in octopus nervous system using a BrdU in vitro administration without exposing the animals to stress or painful injections usually used. This method is in line with the current animal welfare regulations regarding cephalopods, and the flow cytometry-based technique enabled us to measure adult neurogenesis more quickly and reliably than histological techniques, with the additional advantage of processing multiple samples in parallel. Flow cytometry is thus an appropriate technique for measuring and comparing adult neurogenesis in animals that are in a different physiological and/or environmental contexts. A BrdU immunoreactivity distribution, to define the neurogenic areas, and the effective penetration in vitro of the BrdU is also provided.

Recent progress in animal welfare legislation stresses the need to treat cephalopod molluscs, such as Octopus vulgaris, humanely, to have regard for their wellbeing and to reduce their pain and suffering resulting from experimental procedures. Thus, appropriate measures for their sedation and analgesia are being introduced. Clinical anesthetics are renowned for their ability to produce unconsciousness in vertebrate species, but their exact mechanisms of action still elude investigators. In vertebrates it can prove difficult to specify the differences of response of particular neuron types given the multiplicity of neurons in the CNS. However, gastropod molluscs such as Aplysia, Lymnaea, or Helix, with their large uniquely identifiable nerve cells, make studies on the cellular, subcellular, network and behavioral actions of anesthetics much more feasible, particularly as identified cells may also be studied in culture, isolated from the rest of the nervous system. To date, the sorts of study outlined above have never been performed on cephalopods in the same way as on gastropods. However, criteria previously applied to gastropods and vertebrates have proved successful in developing a method for humanely anesthetizing Octopus with clinical doses of isoflurane, i.e., changes in respiratory rate, color pattern and withdrawal responses. However, in the long term, further refinements will be needed, including recordings from the CNS of intact animals in the presence of a variety of different anesthetic agents and their adjuvants. Clues as to their likely responsiveness to other appropriate anesthetic agents and muscle relaxants can be gained from background studies on gastropods such as Lymnaea, given their evolutionary history.

The olfactory system in any animal is the primary sensory system that responds to chemical stimuli emanating from a distant source. In aquatic animals "Odours" are molecules in solution that guide them to locate food, partners, nesting sites, and dangers to avoid. Fish, crustaceans and aquatic molluscs possess sensory systems that have anatomical similarities to the olfactory systems of land-based animals. Molluscs are a large group of aquatic and terrestrial animals that rely heavily on chemical communication with a generally dispersed sense of touch and chemical sensitivity. Cephalopods, the smallest class among extant marine molluscs, are predators with high visual capability and well developed vestibular, auditory, and tactile systems. Nevertheless they possess a well developed olfactory organ, but to date almost nothing is known about the mechanisms, functions and modulation of this chemosensory structure in octopods. Cephalopod brains are the largest of all invertebrate brains and across molluscs show the highest degree of centralization. The reproductive behaviour of Octopus vulgaris is under the control of a complex set of signal molecules such as neuropeptides, neurotransmitters and sex steroids that guide the behaviour from the level of individuals in evaluating mates, to stimulating or deterring copulation, to sperm-egg chemical signalling that promotes fertilization. These signals are intercepted by the olfactory organs and integrated in the olfactory lobes in the central nervous system. In this context we propose a model in which the olfactory organ and the olfactory lobe of O. vulgaris could represent the on-off switch between food intake and reproduction.

To validate a nomogram predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy taking into consideration multiparametric-magnetic resonance imaging (mp-MRI) parameters and targeted biopsies in a western European cohort.A total of 473 men diagnosed by targeted biopsies, using software-based MRI-ultrasound image fusion system, and operated by radical prostatectomy with extended pelvic lymph node dissection across 11 Europeans centers between 2012 and 2019 were identified. Area under the curve of the receiver operator characteristic curve, calibration plot and decision curve analysis were used to evaluated the performance of the model.Overall, 56 (11.8%) patients had LNI on final pathologic examination with a median (IQR) of 13 (9-18) resected nodes. Significant differences (all P0.05) were found between patients with and without LNI in terms of preoperative PSA, clinical stage at DRE and mp-MRI, maximum diameter of the index lesion, PI-RADS score, Grade Group on systematic and targeted biopsies, total number of dissected lymph nodes, final pathologic staging and Grade Group. External validation of the prediction model showed a good accuracy with an area under the curve calculated as 0.8 (CI 95% 0.75-0.86). Graphic analysis of calibration plot and decision curve analysis showed a slight underestimation for predictive probability for LNI between 3% and 22% and a high net benefit. A cut-off at 7% was associated with a risk of missing LNI in 2.6%, avoiding unnecessary surgeries in 55.9%.We report an external validation of the nomogram predicting LNI in patients treated with extended pelvic lymph node dissection in a western European cohort and a cut-off at 7% seems appropriate.

NKX2-1 mutations have been usually associated with a non-progressive neurological disease. Recent reports revealed a vast variability regarding its clinical expressivity. Aim of this work was widening the Benign Hereditary Chorea neurological, cognitive and behavioral phenotype through the description of a child and her family pedigree. Molecular analysis focused on NKX2-1 gene revealed a novel frameshift mutation in the three-generation members described. Cognitive scales detected a relevant developmental delay, and the clinical observation and Autism Diagnostic Observation Schedule -2 administration allowed the diagnosis of autism spectrum disorder in the proband. Microarray testing, further executed to exclude a double hit contextually provoking the complex neurodevelopmental disorder, revealed the 22q11.2 Duplication Syndrome. This paper may contribute to enlarge Benign Hereditary Chorea variable expressivity and, together with other studies reported in the literature, underlines the need to reconsider the term “benign,” verifying the opportunity of more a complex diagnosis.

White bodies (WB), multilobulated soft tissue that wraps the optic tracts and optic lobes, have been considered the hematopoietic organ of the cephalopods. Its glandular appearance and its lobular morphology suggest that different parts of the WB may perform different functions, but a detailed functional analysis of the octopus WB is lacking. The aim of this study is to describe the transcriptomic profile of WB to better understand its functions, with emphasis on the difference between sexes during reproductive events. Then, validation via qPCR was performed using different tissues to find out tissue-specific transcripts. High differentiation in signaling pathways was observed in the comparison of female and male transcriptomic profiles. For instance, the expression of genes involved in the androgen receptor-signaling pathway were detected only in males, whereas estrogen receptor showed higher expression in females. Highly expressed genes in males enriched oxidation-reduction and apoptotic processes, which are related to the immune response. On the other hand, expression of genes involved in replicative senescence and the response to cortisol were only detected in females. Moreover, the transcripts with higher expression in females enriched a wide variety of signaling pathways mediated by molecules like neuropeptides, integrins, MAPKs and receptors like TNF and Toll-like. In addition, these putative neuropeptide transcripts, showed higher expression in females’ WB and were not detected in other analyzed tissues. These results suggest that the differentiation in signaling pathways in white bodies of O. maya influences the physiological dimorphism between females and males during the reproductive phase.

Nitric oxide (NO) signaling is involved in numerous physiological processes in mollusks, e.g., learning and memory, feeding behavior, neural development, and defence response. We report the first molecular cloning of NOS mRNA from a cephalopod, the cuttlefish Sepia officinalis (SoNOS). SoNOS was cloned using a strategy that involves hybridization of degenerate PCR primers to highly conserved NOS regions, combined with RACE procedure. Two splicing variants of SoNOS, differing by 18 nucleotides, were found in the nervous system and the ink gland of Sepia. In situ hybridization shows that SoNOS is expressed in the immature and mature cells of the ink gland and in the regions of the nervous system that are related to the ink defence system.

In this study we have focused the attention on the morphological and functional characterization of the haemocytes from Octopus vulgaris as the first responsible of the innate immunity. Three major haemocytes types were identified by light microscopy based on nucleus/cytoplasm ratio and the presence or absence of cytoplasm granules: haemoblast-like cells, hyalinocytes and granulocytes. The presence of three haemocyte populations was also confirmed by flow cytometry. A cytochemical characterization shows their different activities responsible of the humoral response. Using plate radial diffusion method we demonstrated the bactericidal activity of haemocytes in the presence of different bacteria strains. In order to investigate the presence of soluble biotic compounds responsible of the antibacterial activity, using disc diffusion method and the minimum inhibitory concentration, we have also tested the methanolic acid extract from these cells. Our results pave the way for the development of potent antibacterial drugs that could lead to many applications.