Epididymal more than testicular abnormalities are associated with the occurrence of antisperm antibodies as evaluated by the MAR test.

STUDY QUESTION: Is there any association between mixed antiglobulin reaction (MAR) test positivity and clinical features or genital tract ultrasound (US) parameter values in males of infertile and fertile couples? STUDY ANSWER: In males of infertile and fertile couples MAR test positivity was associated with clinical and US features suggestive of chronic epididymal inflammation. WHAT IS KNOWN ALREADY: MAR test positivity has been more often reported in males of infertile couples than in fertile men. A positive MAR test has been detected in men with a history of testicular or post-testicular damage. No previous study has reported US alterations related to MAR test positivity. This is the first study that has systematically evaluated associations between a positive MAR test and clinical, seminal and US characteristics of the entire male genital tract. STUDY DESIGN, SIZE, DURATION: This cross-sectional analysis included 109 fertile men and 699 consecutive subjects seeking medical care for couple infertility from September 2012 to September 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All subjects underwent, in our outpatient clinic, a complete physical, endocrine, scrotal and transrectal US evaluation and semen analysis (including sIL-8) on the same day. Of the 699 males of infertile couples, 181 (age 38.6 ± 6.6 years) had an assessable MAR test, whereas the test was assessable in all 109 fertile men (age 36.6 ± 5.2 years). The associations among MAR test positivity and the other studied parameters were investigated on a caseload of 290 men (patients + fertile men) and in the two cohorts of males of infertile and fertile couples. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 181 men of infertile couples studied, 20 (11%) had a positive MAR test, including 12 (6.6%) who had a MAR test ≥ 50%, which is considered as a pathological threshold according to the WHO. Of the 109 fertile men, four (3.7%) had a positive MAR test, of which one (0.9%) had a MAR test ≥ 50%. MAR test positivity was therefore found more often in men of infertile couples (P < 0.05). In the entire caseload (n = 290) of males of both infertile and fertile couples, no correlations between MAR test positivity and seminal characteristics were observed. A positive MAR test was associated with epididymal US abnormalities, particularly with the mean size of the epididymal body and tail (both P < 0.0001), and in infertile men, a positive MAR test was also associated with an abnormal epididymal echotexture. In addition, subjects with a positive MAR test more frequently showed a history of epididymitis and high sIL-8 levels. Considering endocrine parameters, only a positive correlation between MAR test positivity and LH levels was observed, even after adjusting for age and life-style factors (adj. r = 0.232, P < 0.0001), while no associations with testosterone and FSH levels were found. LIMITATIONS, REASONS FOR CAUTION: Antisperm antibodies (ASA) were detected in this study by using the SpermMAR test IgG, but other tests are available. In addition, for technical reasons, the MAR test is not assessable in subjects with severe oligo-astheno-zoospermia and, therefore, this test may lead to an intrinsic selection bias. Finally, owing to the cross-sectional nature of the study, neither a causality hypothesis nor mechanistic models can be inferred. WIDER IMPLICATIONS OF THE FINDINGS: First, our results indicate that MAR test positivity is associated with clinical and US signs suggestive of chronic epididymal inflammation and not testicular damage. Hence, when investigating a subject with a positive MAR test, the epididymis and not just the testis should be evaluated. Furthermore, MAR test positivity was more often detected in males of infertile couples than in fertile men, but it was not associated with conventional semen parameter values. Our data support a role of ASA in couple infertility, regardless of the conventional sperm analysis. How ASA affects couple fertility needs to be addressed by further studies. STUDY FUNDING/COMPETING INTEREST(S): Grants were received from the Ministry of University and Scientific Research (SIR project to F.L., protocol number: RBSI14LFMQ). There are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Surgical margin marking for high-risk basal cell carcinomas of the cephalic region: a single-centre experience.

AIM: Mohs micrographic surgery is the treatment of choice for basal cell carcinomas (BCCs) at high risk for local recurrence. This procedure is scarcely employed in Italy, even when it appears necessary, for different causes, including high costs, organization problems, or low professional experience with the technique. Aim of this study is to report our experience with the "surgical margin marking", as alternative to standard Mohs micrographic surgery in the management of high-risk BCCs of the head and neck region. METHODS: A retrospective analysis on 102 (64 males and 38 females; mean age: 66.8 years; median: 68 years; range: 53-87 years) of 208 patients with high-risk basal cell carcinomas of the head and neck region, submitted to surgical margin marking has been made. All cases had completed a 3-year follow-up. Primary tumours were 52 (51%), recurrent tumours were 50 (49%). RESULTS: The mean number of micrographic surgery stages for a complete tumour clearance was 1.65 (range: 1-4 stages). In 47% (N.=49) of cases the tumours were removed by a single stage, while in 42.1% (N.=43) of patients two stages were required. Only 2 patients (2%) showed recurrences during a mean follow-up of 61.2 months (median: 62 months; range: 37-84 months). CONCLUSION: Our experience supports the effectiveness of the surgical margin marking technique in the treatment of high-risk basal cell carcinomas of the cephalic region. It may represent an alternative approach to Mohs micrographic surgery in dermatologic departments of many hospitals, where standard Mohs micrographic surgery is more difficult to perform.

Ancient and historic steel in Japan, India and Europe, a non-invasive comparative study using thermal neutron diffraction.

The production and refinement of steel has followed very different paths in different parts of the Eurasian continent. In aiming to characterize the similarities and differences between various smelting and smithing methods, we have analysed steel samples from four different areas and historic periods: the Koto Age in Japan (twelfth-sixteenth century), the Moghul Empire in India (seventeenth-nineteenth century), the Ottoman Turkish Empire (seventeenth century) and the late Middle Ages (fifteenth century) in Italy. The best quality steel was employed for forging arms and armour of high quality, so that we have selected samples from Japan, India, the Middle East and Italy belonging to such a category. Traditional methods, such as metallography, used to characterize different steels in terms of their carbon contents, microconstituents and slag inclusions, entailed an invasive approach. Since many of the selected artefacts are in a very good state of conservation, a different and non-invasive approach was desirable. To this aim, we have used time of flight neutron diffraction on the Italian Neutron Experimental Station diffractometer, located at the pulsed neutron source ISIS in the United Kingdom. By this technique, we were able to quantify the phase distribution of the metal phases, the slag inclusion content, and the oxidation state of the samples, both as average concentration on the whole artefact and in selected gauge volumes. The results of the present investigation offer an interesting picture of the steel metallurgy in different areas of the world.

The prediction of protein-protein interacting sites in genome-wide protein interaction networks: the test case of the human cell cycle.

In this paper we aim at investigating possible correlations between the number of putative interaction patches of a given protein, as inferred by an algorithm that we have developed, and its degree (number of edges of the protein node in a protein interaction network). We focus on the human cell cycle that, as compared with other biological processes, comprises the largest number of proteins whose structure is known at atomic resolution both as monomers and as interacting complexes. For predicting interaction patches we specifically develop a HM-SVM based method reaching 71% overall accuracy with a correlation coefficient value equal to 0.43 on a non redundant set of protein complexes. To test the biological meaning of our predictions, we also explore whether interacting patches contain energetically important residues and/or disease related mutations and find that predicted patches are endowed with both features. Based on this, we propose that mapping the protein with all the predicted interaction patches bridges the molecule to the interactome at the cell level. To test our hypothesis we downloaded interaction data from interaction data bases and find that the number of predicted interaction patches significantly correlates (Pearson correlation value >0.3) with the number of the known interactions (edges) per protein in the human interactome, as contained in MINT and IntAct. We also show that the correlation increases (Pearson correlation value >0.5) when the subcellular co-localization and the co-expression levels of the interacting partners are taken into account.

Characterization of copper alloys of archaeometallurgical interest using neutron diffraction: a systematic calibration study.

Neutron diffraction experiments have been performed on laboratory-prepared samples of copper alloys to determine their microscopic phase characteristics. The aim of this experiment is to set up a database that can be used in future neutron diffraction measurements on metal samples mainly of archaeological interest.

Neutron diffraction characterization of Japanese artworks of Tokugawa age.

Neutron time-of-flight diffraction technique has been used to characterize some Japanese historical artifacts. With this method, metal samples can be analyzed in their bulk properties without need of sampling. Results shown here were obtained at the Italian Neutron Experimental Station (INES@ISIS) located at the pulsed neutron source ISIS (UK). The parallel use of a scanning electron microscope equipped with an energy-dispersive X-ray fluorescence device (SEM-EDX) permitted a full quantitative characterization of the investigated samples, namely four hand-guards (Tsubas) of Japanese swords attributed to the Tokugawa age. In particular, we were able to obtain, in a totally non-invasive non-destructive way, a full quantitative phase characterization of the samples, a detailed Bragg peak broadening analysis, and a quantitative texture determination. These results, complemented with those obtained via the traditional analysis method of SEM-EDX, allowed a full characterization of both the bulk and the surface of the artifacts.

The effect of backbone on the small-world properties of protein contact maps.

In the last years, small-world behavior has been extensively described for proteins, when they are represented by the undirected graph defined by the inter-residue protein contacts. By adopting this representation it was possible to compute the average clustering coefficient (C) and characteristic path length (L) of protein structures, and their values were found to be similar to those of graphs characterized by small-world topology. In this comment, we analyze a large set of non-redundant protein structures (1753) and show that by randomly mimicking the protein collapse, the covalent structure of the protein chain significantly contributes to the small-world behavior of the inter-residue contact graphs. When protein graphs are generated, imposing constraints similar to those induced by the backbone connectivity, their characteristic path lengths and clustering coefficients are indistinguishable from those computed using the real contact maps showing that L and C values cannot be used for 'protein fingerprinting'. Moreover we verified that these results are independent of the selected protein representations, residue composition and protein secondary structures.

Localized lymphatic sporotrichosis after fish-induced injury (Tilapia sp.).

Localized lymphatic sporotrichosis generally develops after the fungus Sporothrix schenckii is traumatically introduced into skin or mucosa by contaminated plant material. An 18-year-old male fisherman was injured by spines of the dorsal fin of a fish on the left third finger. The lesion became ulcerated, edematous and suppurative and did not respond to tetracycline and cephalexin. Fifteen days after the accident, a nodular lymphangitic pattern of swelling was observed. Histopathological findings and an intradermal test were suggestive of sporotrichosis and mycological cultures confirmed the diagnosis. The lesions resolved after oral treatment with potassium iodide. Sporotrichosis is a common subcutaneous mycosis in Brazil, and there is a previous report in the literature of this disease being acquired via trauma involving fish spines.

Cognitive and affective disorders associated to HIV infection in the HAART era: findings from the NeuroICONA study. Cognitive impairment and depression in HIV/AIDS. The NeuroICONA study.

OBJECTIVE: To assess the natural story of HIV-associated affective and cognitive disorders and the relationship with clinical, pharmacological, immunological and behavioural factors. METHOD: A total of 395 HIV-positive patients, naive to Highly Active Antirectroviral therapy (HAART), with no severe psychiatric disorders have been enrolled in the Neuro-ICONA Study. All participants were administered a comprehensive data collection instrument including an addiction behaviour survey, a medical problem list, a psychiatric assessment, a validated neuropsychological test battery. RESULTS: The global prevalence of cognitive impairment and of prominent depressive symptomatology were 17.9 and 15.5%, respectively. A significant difference in the prevalence of prominent depressive symptomatology was observed between patients in HAART and those not taking HAART(14.1 vs. 23.8%; P = 0.05). CONCLUSION: Depressive and cognitive disorders affect a substantial proportion of HIV-seropositive subjects. The prevalence of prominent depressive symptomatology appears to significantly vary in relationship to the therapeutic protocol.

Tarlov cyst as a rare cause of S1 radiculopathy: A case report.

A 37-year-old female physician presented with a chief complaint of left posterior thigh pain, which began insidiously approximately 4 months before her initial examination. Initially, she had been evaluated by her physician, and magnetic resonance imaging (MRI) was ordered. The MRI scan was reported to be within normal limits, with the exception of minimal disc bulging at L4-5. She had received physical therapy with little benefit and was referred for physiatric assessment. Review of the patient's original MRI scan showed the presence of perineurial (Tarlov) cysts within the sacral canal at the level of S2, with compression of the adjacent nerve root. Subsequent electrodiagnostic testing showed axonal degeneration consistent with an S1 radiculopathy. Tarlov cysts can be a rare cause of lumbosacral radiculopathy and should be considered in the differential diagnosis of radicular leg pain.

Reliability and validity of the DSM-IV diagnostic category of schizoaffective disorder: preliminary data.

BACKGROUND: Concerns have been expressed about the reliability and validity of the DSM-IV criteria for schizoaffective disorder, but no systematic study has been published up to now. METHODS: The Cohen's kappa for the individual items of the DSM-IV definition of schizoaffective disorder, manic episode and major depressive episode was evaluated in 150 patients independently interviewed by two psychiatrists using the Composite International Diagnostic Interview. The two-year outcome of patients with a consensus DSM-IV diagnosis of schizoaffective disorder was compared to that of patients with DSM-IV schizophrenia and schizophreniform disorder, using the Strauss-Carpenter Outcome Scale. RESULTS: The Cohen's kappa was 0.22 for the diagnosis of schizoaffective disorder, 0.71 for that of manic episode, and 0.82 for that of major depressive episode. Schizoaffective patients had a significantly better outcome than those with schizophrenia but a worse outcome than those with schizophreniform disorder. CONCLUSIONS: The inter-rater reliability of the DSM-IV criteria for schizoaffective disorder is not satisfactory. The better outcome of DSM-IV schizoaffective disorder compared with schizophrenia seems to depend more on the inclusion, in the definition of schizophrenia but not in that of schizoaffective disorder, of the six-month duration and functional impairment criteria than on the different symptomatological patterns of the two conditions. LIMITATION: The size of the sample of patients fulfilling DSM-IV criteria for schizoaffective disorder was small. CLINICAL RELEVANCE: The study suggests that the clinical implications of the currently problematic diagnosis of schizoaffective disorder may be modest.

Nutrition and dietary supplements.

Quality and number of subjects in blinded controlled clinical trials about the nutrition and dietary supplements discussed here is variable. Glucosamine sulfate and chondroitin sulfate have sufficient controlled trials to warrant their use in osteoarthritis, having less side effects than currently used nonsteroidal anti-inflammatory drugs, and are the only treatment shown to prevent progression of the disease. Dietary supplements of ephedrine plus caffeine for weight loss (weight loss being the current first line recommendation of physicians for osteoporosis) show some promise, but are not sufficient in number of study subjects. Phenylpropanolamine is proven successful in weight loss. Both ephedrine and phenylpropanolamine have resulted in deaths and hence are worrisome [table: see text] as an over-the-counter dietary supplement. Other commonly used weight loss supplements like Cola acuminata, dwarf elder, Yohimbine, and Garcinia camborgia are either lacking controlled clinical trials, or in the case of the last two supplements, have clinical trials showing lack of effectiveness (although Garcinia has been successful in trials as part of a mixture with other substances, it is unclear if it was a necessary part of the mixture). Safety of these weight loss supplements is unknown. Chromium as a body building supplement for athletes appears to have no efficacy. Creatine may help more in weight lifting than sprinting, but insufficient study subjects and safety information make more studies necessary. Carbohydrate loading is used commonly before endurance competitions, but may be underused as it may be beneficial for other sport performances. Supplements for muscle injury or cramps have had too few studies to determine efficacy. Although proper rehydration with fluids and electrolytes is necessary, a paucity of actual studies to maximize prophylactic treatment for exercise induced cramping still exists. Nutritional supplements for cardiovascular disorders are generally geared to prevention. The United States Department of Agriculture has good recommendations to prevent atherosclerosis; a stricter version by Ornish was shown to reverse coronary heart disease, and the low meat, high fruit, and vegetable DASH diet has been found to decrease hypertension. The epidemiologic studies of hyperhomocysteinemia are impressive enough to give folic acid (or vitamin B6 or B12) supplements to those with elevated homocysteine levels and test patients who have a history of atherosclerotic disease, but no controlled clinical trials have been completed. Soluble fiber has several positive studies in reduction of cholesterol levels and generally is accepted. The data on vitamin E are the most confusing. This vitamin was not helpful in cerebrovascular prevention in China and not helpful at relatively small doses (50 mg) in the United States or Finland against major coronary events. Levels of 400 mg appeared to decrease cardiovascular disease in the United States in studies based on reports by patients and in one large clinical trial. Vitamin E also was successful in prevention of restenosis after PTCA in one clinical trial. Both of these clinical trials need to be repeated in other developed country populations. Some nutritional and dietary supplements are justifiably useful at this point in time. Several meet the criteria of a late Phase 3 FDA clinical trial (where it would be released for public use), but many dietary supplements have insufficient numbers of studies. Some deaths also have occurred with some supplements. If these supplements were required to undergo clinical trials necessary for a new drug by the FDA, they would not be released yet to the public. Several nontoxic supplements appear promising, though need further study. Because they have essentially no toxicity (such as folic acid with B12, soluble fiber, and vitamin E) and may have efficacy, some of these supplementations may be useful now, without randomized clinical trials.

Early neuropsychological impairment in HIV-seropositive intravenous drug users: evidence from the Italian Multicentre Neuropsychological HIV Study.

The aim of the Italian Multicentre Neuropsychological HIV Study is to assess the prevalence and natural history of cognitive deficit in intravenous drug users (i.v.DUs) during the asymptomatic phase of HIV infection. The study is currently being conducted in four centres (Napoli, Benevento, Verona and Pavia) whose catchment areas are characterized by different levels of prevalence of HIV infection. Cognitive evaluation is being performed by means of a standardized neuropsychological test battery. A total of 251 subjects (167 males and 84 females) have been recruited in the cross-sectional phase of the study, including 75 asymptomatic HIV-seropositive i.v.DUs (HIV+/i.v.DUs), 97 HIV-seronegative i.v.DUs (HIV-/i.v.DUs) and 79 non-i.v.DU seronegative controls matched to i.v.DUs with regard to sex, age and educational level. The prevalence of global cognitive impairment (performance at least 1.5 standard deviations worse than the average of the control group, on at least two out of five tests) was significantly higher in HIV+/i.v.DUs than in either HIV-/i.v.DUs (22.7% vs. 8.2%; P < 0.01) or healthy controls (22.7% vs. 2.5%; P < 0.001). The difference between HIV-/i.v.DUs and healthy controls was not statistically significant (8.2% vs. 2.5%; P = 0.19). The results of this study lend further support to the 'cerebral reserve' model. The cerebral reserve could indeed be reduced in i.v.DUs as a consequence of chronic exposure to the substance of abuse, so that these subjects become more vulnerable to direct and indirect neurotoxic effects of HIV.

Long-term outcome of lithium prophylaxis in bipolar disorder: a 5-year prospective study of 402 patients at a lithium clinic.

OBJECTIVE: In this prospective study, information was collected on all bipolar I patients who started lithium prophylaxis at a lithium clinic during more than 15 years. METHOD: Patients were evaluated bimonthly with standardized instruments for as long as they took lithium. Treatment surveillance conformed to internationally accepted guidelines. Five years after starting prophylaxis, each patient was contacted for a follow-up interview. RESULTS: Of the 402 enrolled patients, 27.9% were no longer taking lithium at follow-up; 38.1% were taking lithium and had had at least one recurrence of the disorder; and 23.4% were taking lithium and had had no recurrence. Among patients still taking lithium whose plasma lithium levels had been below 0.5 mmol/liter on no more than 10% of checks, 88.0% had at least a 50% reduction in mean annual time spent in the hospital compared to a reference pretreatment period, and 43.0% had had no recurrence. Patients not taking lithium at follow-up had a poorer outcome than those taking lithium, but patients no longer taking any psychotropic drug did not differ from those taking lithium. Patients no longer taking lithium had had a higher frequency of psychotic features in the index episode than those still taking lithium. CONCLUSIONS: The impact of lithium prophylaxis on the course of bipolar disorder is severely limited by the high dropout rate. In bipolar patients taking lithium regularly for several years, a drastic reduction of time spent in the hospital is almost the rule; these patients represent a self-selected population in which at least one group at high risk of poor outcome is under-represented.

Pityriasis rubra pilaris, lichen planus, alopecia universalis and vitiligo in a patient with chronic viral hepatitis C.

A 43-year-old man, affected with alopecia universalis and vitiligo since his childhood, developed erythrodermic pityriasis rubra pilaris followed then by lichen planus; chronic viral hepatitis C was diagnosed. This appears to be a unique constellation of cutaneous diseases implying both autoimmunity and hepatitis C virus.