Association of quantitative MRI-based radiomic features with prognostic factors and recurrence rate in oropharyngeal squamous cell carcinoma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Treating varicocele in 2018: current knowledge and treatment options.

PURPOSE: Varicocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects. METHODS: We conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: "varicocele", "varicocelectomy", "sclerotherapy", "male infertility", "subfertility", and "semen abnormalities". RESULTS: Data from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach. CONCLUSIONS: Varicocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

Step-by-step illustrated guide to central neck dissection.

BACKGROUND: The incidence of thyroid carcinoma has been increasing worldwide and surgery is the primary treatment. Central compartment dissection of the neck is a very delicate procedure given the risks of recurrent laryngeal nerve injury and hypoparathyroidism. METHODS: This paper gives a detailed description of this surgical technique in a patient affected by papillary carcinoma of the thyroid gland, supported by highly representative iconographic materials from a tertiary department. RESULTS: A stepwise description is provided, along with high-quality pictures and specific tips and tricks. Although neck dissection is a well-codified procedure, the fine details of this surgical technique are not currently available and are still the prerogative of the expert surgeon. CONCLUSION: The central neck compartment contains several vulnerable structures; damage to these structures would affect patients' lives, possibly permanently. Anatomical knowledge and standardisation are needed for all surgeons, particularly new surgeons (such as residents) who cannot rely simply on experience.

Laboratory Scale Evaluation of Fertiliser Factory Wastewater Treatment through Membrane Distillation and Reverse Osmosis.

The incumbent water stress scenario imposes wastewater valorisation to freshwater, promoting technology for its effective treatment. Wastewater from fertiliser factories is quite problematic because of its relevant acidity and solute content. Its treatment through vacuum membrane distillation (VMD) was evaluated through laboratory scale tests at 40 °C and 25 mbar vacuum pressure with polytetrafluoroethylene and polypropylene flat-sheet porous membranes. The wastewater from a partially disused Italian industrial site was considered. VMD distillate fluxes between 22 and 57.4 L m-2 h-1 (LMH), depending on the pore size of the membranes, along with very high retention (R > 99%) for anions (Cl-, NO3-, SO42-, PO43-), NH4+, and chemical oxygen demand (COD) were observed. Laboratory scale reverse osmosis (RO) tests at 25 °C and increasing of the operating pressure (from 20 bar to 40 bar) were carried out with a seawater desalination membrane for comparison purposes. Permeability values around 1.1 LMH/bar almost independently of the operating pressure were observed. Lower retentions than those measured from VMD tests were found. Finally, for any given RO operating pressure, the flux recovery ratio (FRR) calculated from permeate fluxes measured with pure water before and after wastewater treatment was always much lower that evaluated for VMD membranes.

Effects of Parkinson's disease on proprioceptive control of posture and reaching while standing.

Although previous studies have shown pointing errors and abnormal multijoint coordination in seated subjects with Parkinson's disease (PD) who cannot view their arm, the extent to which subjects with PD have problems using proprioception to coordinate equilibrium maintenance and goal-oriented task execution has not been adequately investigated. If a common motor program controls voluntary arm pointing movements and the accompanying postural adjustments, then impairments of proprioceptive integration in subjects with PD should have similar effects on pointing and body center of mass (CoM) control with eyes closed. Ten standing subjects with PD (OFF-medication) and 10 age-matched control (CTR) subjects pointed to a target with their eyes closed and open. Although pointing accuracy was not significantly different between groups, body CoM displacements were reduced in subjects with PD, but not in CTR, when eyes were closed. In addition, with eyes closed, PD subjects showed reduced temporal coupling between pointing and CoM velocity profiles and reduced spatial coupling between pointing and CoM endpoints. This poor coupling with eyes closed could be related to the PD subjects' increased jerkiness of CoM displacements. The different effects of eye closure between CTR and PD subjects on the CoM displacements, but not pointing accuracy, are consistent with separate motor programs for the pointing and postural components of this task. Furthermore, the decoupling between the two movement components in subjects with PD when they could not use vision, suggests that the basal ganglia are involved in the integration of proprioceptive information for posture-movement coordination.

Physiological mechanisms for stabilizing the limb when acting against physical constraints.

Smooth physical interaction with our environment, such as when working with tools, requires adaptability to unpredictable perturbations that can be achieved through impedance control of multi-joint limbs. Modulation of arm stiffness can be achieved either increasing co-contraction of antagonistic muscles or by increasing the gain of spinal reflex loops. According to the "automatic gain scaling" principle, the spinal reflex gain, as measured via the H-reflex, scales with muscle activation. A previous experiment from our labs suggested, however, that reflex gains might instead be scaled to the force exerted by the limb, perhaps as a means to counteract destabilizing external forces. The goal of our experiment was to test whether force output, rather than the muscular activity per se, could be the critical factor determining reflex gain. Five subjects generated different levels of force at the wrist with or without assistance to dissociate applied force from agonist muscular activity. We recorded contact force, EMG and H-reflex response from a wrist flexor. We did not find a strict relationship between reflex gain and contact force but nor did we observe consistent modulation of reflex gain simply as a function of agonist muscle activity. These results are discussed in relation to the stability of the task constraints.

Effect of Organic Acids on Salmonella Shedding and Colonization in Pigs on a Farm with High Salmonella Prevalence.

This study builds on the results of a previous study in which six commercial feed products based on organic acids were evaluated with respect to Salmonella contamination of piglets in an artificially challenged seeder model. In the present study, the efficacy of three of these commercial products was assessed for Salmonella reduction in fattening pigs on one closed farm with a natural high Salmonella prevalence. In each of four fattening compartments, one of the following feed treatments was evaluated during two consecutive fattening rounds: (i) butyric acid (active ingredients at 1.3 kg/ton of feed; supplement A1), (ii) a combination of short-chain organic acids (mixture of free acids and salts) and natural extracts (2.92 kg/ton; supplement A4), (iii) a 1:1 blend of two commercial products consisting of medium-chain fatty acids, lactic acid, and oregano oil (3.71 kg/ton; supplement A5+A6), and (iv) a control feed. On the farm, the Salmonella status of the fattening pigs was evaluated by taking fecal samples twice during the fattening period. At the slaughterhouse, samples were collected from the cecal contents and the ileocecal lymph nodes. Salmonella isolates were serotyped and characterized by pulsed-field gel electrophoresis. This farm had a particularly high number of pigs shedding Salmonella with a wide variety of sero- and pulsotypes. Only the feed blend based on the medium-chain fatty acids was able to significantly reduce Salmonella prevalence both on the farm and at the slaughterhouse. With this combined supplement, the Salmonella reduction in the feces at slaughter age, in cecal contents at slaughter, and the lymph nodes was 50, 36, and 67%, respectively, compared with the control animals. This promising finding calls for further investigation including cost-efficiency of this combined feed product and its effect on the animals.

Evaluation of theories of complex movement planning in different levels of gravity.

Due to high redundancy of degrees of freedom in the human body, we can perform any movement, from the simplest to the most complex, in many different ways. Several studies are still trying to identify the motor strategies that master this redundancy and generate the movements whose characteristics are highly stereotyped. The aim of this work is to build a simulator that is able to evaluate different motor planning hypotheses. The most interesting applications of this tool occur in studies of the motor strategy in microgravity conditions. The comparison between simulated movements and kinematics data recorded both on Earth, and during a 5-month mission on board the Mir station shows that for a complex whole-body movement (such as trunk bending) a single planning criterion cannot explain all movement aspects. However, the simulator allows an understanding of the motor planning adaptation of astronauts. In space, the lack of equilibrium constraint (which on Earth brings about the center of mass control) leads to a new motor strategy that minimizes dynamic interactions with the floor.

Chronic treatment with pirenzepine decreases growth hormone secretion in insulin-dependent diabetes mellitus.

We and others previously reported that nocturnal GH secretion in patients with insulin-dependent diabetes mellitus is blunted by acute cholinergic muscarinic blockade with pirenzepine. In this study, we investigated whether this inhibitory effect on GH secretion persists during chronic pirenzepine administration, and if pirenzepine administration affects glycemic control. Nocturnal GH secretion was studied from 2300-0800 h before and after one month of pirenzepine administration (100 mg/day, orally, given at 2300 h) in 13 diabetic patients receiving their usual insulin treatment. GH secretion (GH area under curve) was blunted after pirenzepine administration [mean, 877 +/- 215 (+/- SE) vs. 1407 +/- 311 micrograms/L.min; P less than 0.002]. During pirenzepine administration, hemoglobin A1c significantly decreased (P less than 0.02), and 4 of the 13 patients had lower daily insulin requirements (5-23 U/day), but there was no significant change for the group as a whole. These results indicate that the inhibitory effect of pirenzepine on GH secretion persists when pirenzepine is given chronically and that pirenzepine seems to improve the metabolic control of the patients.

Platelet cNOS activity is reduced in patients with IDDM and NIDDM.

Several studies in vitro and in vivo suggest that the nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to vascular alteration facilitating platelet-vascular wall interaction, adhesion of monocytes to endothelium, vascular smooth muscle proliferation and by decreasing endothelium-dependent vasodilation. In this study we evaluated the activity of the constitutive nitric oxide synthase (cNOS) in platelets of patients with insulin-dependent diabetes mellitus (IDDM) and with non-insulin-dependent diabetes mellitus (NIDDM). When compared to that of normal subjects, cNOS activity is significantly lower in patients with IDDM and with NIDDM (1.57 +/- 0.25 vs. 0.66 +/- 0.10 fmol/min/10(9) PLTs and 1.57 +/- 0.25 vs. 0.67 +/- 0.08, respectively; p<0.005). These data demonstrate that the platelet cNOS activity is decreased in diabetes mellitus.

Calcium blood level modulates endogenous nitric oxide action: effects of parathroidectomy in patients with hyperparathyroidism.

UNLABELLED: Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840). IN CONCLUSION: (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.

Cortical plasticity of spatial stimulus-response associations: electrophysiological and behavioral evidence.

Right-handed subjects tend to respond faster to stimuli presented in the visual hemifield that spatially corresponds to the responding hand. In a typical Simon task, response is based on a non-spatial salient feature of the stimulus (e.g. color) whereas its position must be ignored. However, the spatial position of the stimulus interferes with the processing of the salient characteristic. Subjects are significantly faster when stimulus side and response side correspond (corresponding condition) than when they do not (non-corresponding condition). We have previously shown with behavioral experiments that, when subjects practice reversed contingencies (that is, spatially incompatible trials) in a session preceding the Simon task, they show a long-term retention of these associations, resulting in the disappearance of the latency cost typically observed in non-corresponding trials. Here we show, by means of the lateralized readiness potential, that the neural correlate of such behavioral plasticity is an increase in premotor cortex activation during preparation of non-corresponding responses. This effect showed a marked left-right asymmetry which suggests an important role of subjects' handedness. Our results demonstrate that humans can learn in a single session to reverse relatively stable stimulus-response associations.

The role of long-term-memory and short-term-memory links in the Simon effect.

In Experiment 1, children performed a Simon task after a spatially compatible or incompatible task. Results showed a Simon effect after the spatially compatible task and a reversed Simon effect after the spatially incompatible task. In Experiments 2-5, an identical procedure was adopted with adult participants, who performed the Simon task immediately after, a day after, or a week after the spatial compatibility task. Experiment 6 established a baseline for the Simon effect. Results showed a Simon effect after the spatially compatible task and no Simon effect or a reversed Simon effect after the spatially incompatible task. A modified version of the computational model of M. Zorzi and C. Umiltà (1995) was used to compare possible accounts of the findings. The best account exploits 2 types of short-term-memory links between stimulus and response and their interaction with long-term-memory links.

Autoimmune thyroid diseases and coeliac disease.

BACKGROUND: Coeliac disease may be associated with a wide variety of diseases of known or suspected immunological aetiology. OBJECTIVE: To screen for both (a) the prevalence of coeliac disease in adults with autoimmune thyroid diseases, and (b) thyroid impairment among adults with coeliac disease, as compared to sex- and age-matched controls. DESIGN: Prospective cohort study. SETTING: University teaching hospital. PATIENTS: A total of 152 consecutive adults with autoimmune thyroid diseases, 185 consecutive coeliac disease patients (53 newly diagnosed and 132 already on a gluten-free diet) and 170 sex- and age-matched controls. METHODS: Screening for coeliac disease was done by means of IgA anti-endomysium antibodies, detected by indirect immunofluorescence on monkey oesophagus. Patients with positive sera underwent duodenal biopsy for diagnostic confirmation. Thyroid function was assessed by measuring the levels of serum thyroid-stimulating hormone, free T3, free T4, thyroperoxidase and thyroid microsome antibodies. Autoimmune thyroid diseases were classified according to the American Thyroid Association guidelines. RESULTS: Anti-endomysium antibodies were positive in five of 152 autoimmune thyroid disease patients (3.3%) and coeliac disease was histologically confirmed in all: this prevalence is 10-fold higher than expected. Only one patient presented with gastrointestinal complaints, but iron deficiency was found in three and alterations at bone mineralometry in all. The overall prevalence of autoimmune thyroid diseases was significantly higher (38/185, 20.5%) in coeliac patients than in controls (19/170, 11.2%). The prevalence of both hypo- and hyperthyroidism was not different from that of controls, while the prevalence of autoimmune thyroid disease with euthyroidism was 13% in patients and 4.7% in controls. CONCLUSIONS: The association of coeliac disease with autoimmune thyroid disease is not surprising as they share common immunopathogenetic mechanisms. It is advisable to screen autoimmune thyroid disease patients for coeliac disease as there is an increased risk for gluten intolerance. In contrast, thyroid function assessment in coeliac disease patients is probably less justified, although the need for a strict clinical follow-up of those patients with euthyroidism and autoimmune thyroid disease, who could develop overt thyroid impairment, remains an open question.

Multiple endocrine neoplasia (MEN IIB) with Cushing's syndrome due to medullary thyroid carcinoma producing corticotropin-releasing hormone.

We describe a case of Cushing's syndrome caused by a medullary thyroid carcinoma (MCT) secreting corticotropin-releasing-hormone (CRH) in a young woman presenting mucosal neuromas located on the top of the tongue and eyelid areas. Laboratory studies showed, basally and after dexamethasone suppression test, serum cortisol and plasma pituitary corticotrophin (ACTH) levels agreed with an ectopic Cushing's syndrome. Immunohistochemical studies of the MCT tissue revealed a production of CRH and scattered cells containing vasopressin but not ACTH peptides. This is the first demonstrated case of a CRH-secreting tumor in multiple endocrine neoplasia (MEN IIB) syndrome.

A new approach in the evaluation of gonadotropins for the diagnosis of polycystic ovary syndrome.

The new immunometric methods using monoclonal antibodies to detect gonadotropins revealed a reduction in the absolute values of these hormones, especially LH, due to a decrease in cross-reaction between gonadotropin subunits. Therefore, reference values of the LH/FSH ratio and their diagnostic significance in the polycystic ovary syndrome (PCOS) need to be defined again. We evaluated the LH/-FSH ratio in basal conditions and after administration of GnRH (100 micrograms as i.v. bolus) in seventy patients with PCOS employing an immunoenzymatic method. In PCOS patients the LH/FSH ratio was greater than 1 in 70% when evaluated on a single sample and in 88% when evaluated on a pooled serum from four samples every 30 minutes; in the control group the ratio was always lower than 1. The LH/-FSH ratio evaluated on the peak values in response to GnRH was greater than 2 in all patients and lower than 2 in the control group. Our results indicate that the LH/FSH ratio is still an important diagnostic tool in PCOS, especially when evaluated on the peak values in response to GnRH, even if its reference values are lower using these new monoclonal methods.

Bone metabolism in type 2 diabetes mellitus.

Several conditions have been described to cause osteoporosis, including diabetes mellitus. While the relationship between type 1 diabetes and osteopenia is well documented in the literature, data on the presence of this complication in type 2 diabetes have not been well established. We studied a population composed of 66 post-menopausal women with type 2 diabetes and a control population. We examined bone mineral density with the dual-energy X-ray absorptiometry (DXA) technique at the lumbar and femoral levels and, in a subgroup of patients, we also measured the levels of markers of bone remodelling. We found significantly higher levels of bone mineral density at the femoral (but not lumbar) level in the diabetic subjects compared with the control population in all the examined subregions, except Ward's triangle. Moreover, we found higher levels of some markers of bone resorption (urinary calcium and hydroxyproline, telopeptide) in the patients with diabetes, while urinary crosslinks were higher in the controls. On the basis of these results, we suggest that osteoporosis cannot be considered a complication of type 2 diabetes and that, from a metabolic point of view, bone resorption is greater in diabetic patients than in normal subjects, as suggested by the high levels of most of the markers of osteoclastic activity.

[Hormonal control of sexual behavior in males and endocrinologic causes of sexual dysfunction]. / Il controllo ormonale del comportamento sessuale nel maschio e cause endocrinologiche di disfunzione sessuale.

The role of androgens in the male sex differentiation, in the genesis and preservation of the erectile function is summarized. In sex differentiation, testosterone acts on genitalia and central nervous system (CNS). In CNS sexual steroids exert a morphogenetic action during neuronal development. At the pubertal age, the increase of testosterone leads to the development of sex characteristics, the onset of libido and the beginning of the nocturnal spontaneous erectile function. Spontaneous erections are androgen-dependent, and they are impaired in androgen deficiency. Normal androgen levels lead to make voluntary erections. However, in the human species, cortical influences may greatly affect what could be possible to occur in relation to the hormonal situation. Endocrine causes of sexual dysfunction are responsible for about 20-25% of the total; among these primary and secondary hypogonadisms are the most frequent and they are to be managed with causal treatments and androgen replacement therapy. Therefore, androgen treatments are not useful in functional sex disorders and they may be at risk on prostatic tissue. Andropause is related to a progressive reduction of testicular function, principally due to vascular disorders, with low-normal androgen levels. On the basis of these observations it is underlined that in the human species the androgen presence is a necessary but not sufficient condition for a correct sex function.