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Background UltraViolet-C (UV-C) lamps may be used to supplement current hospital cleaning and disinfection of surfaces contaminated by SARS-CoV-2. Our aim is to provide some practical indications for the correct use of UV-C lamps. Methods We studied three UV-C lamps, measuring their spatial irradiance and emission over time. We quantify the error that is committed by calculating the irradiation time based exclusively on the technical data of the lamps or by making direct irradiance measurements. Finally, we tested specific dosimeters for UV-C. Results Our results show that the spatial emission of UV-C lamps is strongly dependent on the power of the lamps and on the design of their reflectors. Only by optimizing the positioning and calculating the exposure time correctly, is it possible to dispense the dose necessary to obtain SARS-CoV-2 inactivation. In the absence of suitable equipment for measuring irradiance, the calculated irradiation time can be underestimated. We therefore consider it precautionary to increase the calculated times by at least 20%. Conclusion To use UV-C lamps effectively, it is necessary to follow a few simple precepts when choosing, positioning and verifying the lamps. In the absence of instruments dedicated to direct verification of irradiance, photochromic UV-C dosimeters may represent a useful tool for easily verifying that a proper UV-C dose has been delivered.

Background UltraViolet-C (UV-C) lamps may be used to supplement current hospital cleaning and disinfection of surfaces contaminated by SARS-CoV-2. Our aim is to provide some practical indications for the correct use of UV-C lamps. Methods We studied three UV-C lamps, measuring their spatial irradiance and emission over time. We quantify the error that is committed by calculating the irradiation time based exclusively on the technical data of the lamps or by making direct irradiance measurements. Finally, we tested specific dosimeters for UV-C. Results Our results show that the spatial emission of UV-C lamps is strongly dependent on the power of the lamps and on the design of their reflectors. Only by optimizing the positioning and calculating the exposure time correctly, is it possible to dispense the dose necessary to obtain SARS-CoV-2 inactivation. In the absence of suitable equipment for measuring irradiance, the calculated irradiation time can be underestimated. We therefore consider it precautionary to increase the calculated times by at least 20%. Conclusion To use UV-C lamps effectively, it is necessary to follow a few simple precepts when choosing, positioning and verifying the lamps. In the absence of instruments dedicated to direct verification of irradiance, photochromic UV-C dosimeters may represent a useful tool for easily verifying that a proper UV-C dose has been delivered.

The potential virucidal effects of UV-C irradiation on SARS-CoV-2 were experimentally evaluated for different illumination doses and virus concentrations (1000, 5, 0.05 MOI). At a virus density comparable to that observed in SARS-CoV-2 infection, an UV-C dose of just 3.7 mJ/cm2 was sufficient to achieve a more than 3-log inactivation without any sign of viral replication. Moreover, a complete inactivation at all viral concentrations was observed with 16.9 mJ/cm2. These results could explain the epidemiological trends of COVID-19 and are important for the development of novel sterilizing methods to contain SARS-CoV-2 infection.

Affecting 2.5 million people worldwide, multiple sclerosis (MS) is one of the main causes of acquired disability among young adults. In French West Indies (FWI), where MS has arisen from the end of the 80's, a low therapeutic response to interferons beta1 (IFN beta1) in patients of African descent, restrains the therapeutic options. Fingolimod is a Sphingosine-1-Phosphate receptor modulator whose efficacy in the treatment of MS has recently been shown in three phase III studies. Nevertheless, data are currently lacking concerning the use of Fingolimod among populations of African descent, particularly in a real-world setting. Efficacy and safety information collected during the first two years of follow-up have been analysed retrospectively for all patients in whom Fingolimod treatment was introduced in FWI between its marketing date and December 2015. Fifty-two consecutive patients with a relapsing remitting MS started Fingolimod therapy in the FWI, according to the European guidelines. After 24 months, 40 patients were still receiving the treatment. The average Annualized Relapse Rate (ARR) dropped by 81%, and 72.5% of patients remained free from disability progression during the 24 months on Fingolimod. MS remained controlled (according NEDA 3 criteria) for 41% of patients who were still on therapy at 24 months. Nine participants presented with a moderate or major side effect. Unlike IFN beta1 therapy, Fingolimod appears to be effective in Afro-Caribbean patients in a real-world setting with a similar benefit to what has been observed in phase III studies in more selected populations.

Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases. We report nine new IMF cases recently seen at our Fibro-Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006–2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune-mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32 %) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behcet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4-related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders.

To identify bacterial species present in the lower genital tract of males and to investigate the relationship with semen quality.The microscopic analyses and cultures of 696 semen specimens, collected over five years from males investigated for subfertility, were retrospectively assessed.Semen cultures were sterile in 48%; they showed a polymicrobial flora (more than two bacterial species) in 30%, and were positive (1 × 10(3) colony forming units/ml) in 22% of the cases. Gardnerella vaginalis was the most frequently isolated bacterium, followed by Escherichia coli and Enterococcus sp. Ureaplasma urealyticum was recovered from 13 of 147 samples (9%). Of patients with bacteriospermia 42% had leukospermia (10(6) leukocytes/ml of semen). Bacteriospermia and leukospermia did not correlate with each other although a positive correlation was found between the presence of leukocytes and G. vaginalis isolation. Semen parameters were correlated with the bacterial species isolated most frequently. In comparison with controls, sperm concentration, motility and morphology were mostly deteriorated in the presence of G. vaginalis and U. urealyticum.Positive seminal fluid cultures must be interpreted with caution, taking into account both raised colony counts of single isolates and leukocyte concentration in the semen. Thus the common misdiagnosis of genital tract infection, based on the presence of seminal bacteria, and unnecessary treatment with antibiotics may be avoided.

Two forms of competitive encounters namely Randori (free fight) and Kata (highly ritualized fight) were studied in 22 professional male judo fighters. The dyadic, symmetrical (in terms of body weight and fighting ability) encounters were videotaped to assess relationships between agonistic behavior and individual variations in plasma levels of testosterone (T), cortisol (C) and interleukins (IL-6 and IL-1 beta) measured before and after the competition. Unremarkably, winners showed longer attack but devoted less time to defensive behaviors when compared to losers. T increased only during Randori but the individual pre- and post-competition T levels recorded in such fights were strongly correlated with the corresponding measures in the Kata for the same individuals. Interestingly, the pre- and post-Randori competition T levels were higher in losers than in winners and T variations positively correlated with the frequencies of attacks and with the duration of defensive postures. The T response shows individual variation and seems to reflect evaluation of the likelihood of winning or losing. Both Randori and Kata induced a marked C increase, although the pre- and post-Randori hormonal titers were higher than those found for the Kata. IL-6 significantly increased between the pre- and the post-Randori competition, but no such changes occurred during the Kata. No correlations were found between individual pre- and post-competition C and IL-6 and IL-1 beta levels in either Randori or Kata. This suggests that C and cytokine release are unrelated to emotional or cognitive perception of the possible outcome of fighting but are a consequence of general motor activity. Martial arts appear to provide good human models to understand: (a) the relationships between conflict, hormones and the immune system and (b) the relationships between mood and physiological responses to competitive aggression. Language: en

Background: The distinction between Cushing’s disease (Cushing’s syndrome dependent on adrenocorticotropic hormone (ACTH)-secreting tumors of pituitary origin) and pseudo-Cushing’s states (Cushingoid features and hypercortisolism sometimes present in alcoholic, depressed or obese subjects) can present a diagnostic challenge in clinical endocrinology. Recently, the availability of a highly sensitive immunofluorometric assay for the measurement of total prostate-specific antigen (PSA) provided the possibility to measure serum PSA levels in women. Interestingly, PSA gene expression and protein production has been found to be upregulated by steroid hormones, such as androgens, glucocorticoids, mineral corticoids and progestins. In fact, serum total PSA concentrations appear to be higher in female patients with Cushing’s disease than in normal women. We wondered whether a similar phenomenon also occurs in pseudo-Cushing’s state. Methods: In order to answer this question, we compared the serum total PSA levels measured in 10 female subjects with alcohol-dependent pseudo-Cushing’s state with those observed in 8 female patients with Cushing’s disease and in 15 age-matched healthy women. Serum testosterone, ACTH and cortisol, and 24-hour urinary cortisol levels were measured; cortisol suppression after dexamethasone was also tested in all subjects. Results: The basal serum levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing’s disease or pseudo-Cushing’s state; these latter groups showed similar basal hormonal values. Dexamethasone administration was unable to suppress serum cortisol levels in 5 subjects with Cushing’s disease and 6 subjects with pseudo-Cushing’s state. Serum testosterone values in the group with Cushing’s disease were higher than in the other groups. No differences were observed between pseudo-Cushing’s and normal subjects. Serum total PSA levels were significantly higher in women with Cushing’s disease than in subjects with pseudo-Cushing’s state and normal controls; these latter groups showed similar PSA values. When serum total PSA and testosterone levels were considered together, a significant positive correlation was observed in the group with Cushing’s disease, but not in the other groups. Conclusions: These data indicate that the steroid milieu responsible for the elevation in serum PSA in women with Cushing’s disease is not present in subjects with alcohol-dependent pseudo-Cushing’s state, suggesting the possible use of PSA as a marker of differentiation between these pathological conditions in women.

Objective: To establish the role of hyperinsulinemia and hypoglycemia during the insulin tolerance test (ITT) in the regulation of luteinizing hormone (LH) secretion and the location with respect to the blood-brain barrier (BBB) of the glucosensitive areas controlling LH release. Methods: The LH-secretory pattern during an ITT (0.15 IU/kg body weight) was evaluated in 8 normal men during infusion with normal saline (control test), glucose or fructose. Results: lnsulin-induced hypoglycemia produced a significant decrement in serum LH levels in the control test, but not when the concomitant infusion of glucose prevented hypoglycemia. Fructose infusion did not change LH decrease during ITT. Conclusions: These data exclude a direct role of hyperinsulinemia in the mechanism underlying the inhibition of LH secretion during ITT. Furthermore, since glucose but not fructose crosses the BBB, the LH decrease during ITT appears to be generated by hypoglycemia at the level of glucosensitive areas located inside the BBB.

The studies on the factors that regulate the biology of the neuroblastoma cell lines may offer important information on the development of tissues and organs that derive from the neural crest. In the present paper we study the action of epidermal growth factor (EGF) on two human neuroblastoma cell lines: SK-N-SH which is composed at least of two cellular phenotypes (neuroblastic and melanocytic/glial cells), and its pure neuroblastic subclone SH-SY5Y. The results show that EGF (10 ng/ml) significantly stimulates the incorporation of [3H]-thymidine in the SK-N-SH cells only in the presence of fetal bovine serum (FBS) (control = 58,285 +/- 9327 cpm; EGF = 75,523 +/- 4457, p < 0.05). Such effect is not observed in the presence of a chemical defined medium, that is, in the absence of FBS (control = 100,997 +/- 4375; EGF = 95,268 +/- 4683; NS) In the SH-SY5Y cells the EGF does not modify the incorporation of [3H]-thymidine either in the presence of 10% of BFS (control = 113,838 +/- 6978; EGF = 119,434 +/- 9441; NS) or in its absence (control = 46,197 +/- 3335; EGF = 44,472 +/- 3493; NS). The results here reported suggest that: a) EGF may affect the proliferation of cells derived from a primary human neuroblastoma; b) this is evident by the EGF-induced increase of [3H]-thymidine incorporation in SK-N-SH cells; c) it is required the presence of other growth factors, present in the FBS, for the mitogenic action to be accomplished; d) since the pure neuroblastic SH-SY5Y cell line are refractory to the EGF, the effects observed in SK-N-SH cells probably occur on the melanocytic/glial cell subpopulation.

Pizzi M, Arrighi V, Galli P, Memo M, Spano PF. Lack of vasoactive intestinal peptide-releasing property in prolactin cells from ovariectomized rats: contribution of post-transductional impairments. Eur J Endocrinol 1994;130:361–5. ISSN 0804–4643 We have demonstrated recently that in menopausal women and in ovariectomized rats the deficiency of circulating oestrogens impairs vasoactive intestinal peptide (VIP) efficacy in stimulating prolactin (PRL) release. The present study was designed to investigate whether the lack of VIP-induced PRL release after ovariectomy is a consequence of a defect at the receptor-transductional or post-transductional level. For this purpose we evaluated the VIP receptor function, by measuring VIP-stimulated cyclic adenosine monophosphate (AMP) formation, and the efficacy of the cyclic AMP-dependent PRL release in pituitary cells from control and ovariectomized animals. We observed that VIP induced a significantly higher stimulation of adenylate cyclase in pituitary homogenates from ovariectomized rats than in those from control animals. This effect appeared to be linked to an increased efficiency of the Gs coupling protein, because superimposable results were obtained by using the non-hydrolysable guanosine triphosphate (GTP) analogue, 5-guanylylimidodiphosphate. On the contrary, the cyclic AMP analogue, 8-Br-cAMP, that potently stimulated PRL release from control pituitary cells was completely ineffective in cells from ovariectomized rats. The present data indicate that in PRL-secreting cells from ovariectomized rats a defect in the post-transductional mechanism that couples the VIP receptor to PRL secretion, rather than a reduction of receptor function, possibly accounts for the lack of VIP efficacy. Marina Pizzi, Dept. Biomed. Sci. & Biotech., School of Medicine, Via Valsabbina 19, 25123 Brescia, Italy

The growth hormone (GH), cortisol, and arginine vasopressin (AVP) responses to bicycle ergometry (with increasing workload until exhaustion) were measured in 20 patients affected by insulin-dependent diabetes mellitus (IDDM) (10 habitual smokers and 10 nonsmokers) and 20 nondiabetic subjects (normal controls) (10 habitual smokers and 10 nonsmokers). Cardiorespiratory parameters such as heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (V o 2 ), carbondioxide production (V co 2 ), and respiratory exchange ratio (R) were monitored before and during exercise tests. No significant differences between groups were observed; furthermore, there were no differences in circulating somatomedin-C (SM-C) and free fatty acids (FFA) levels between groups. Blood glucose levels were similar before exercise and followed a similar pattern during tests in diabetic smokers and nonsmokers. Basal GH, cortisol, and AVP levels were similar in diabetic smokers, diabetic nonsmokers, normal smokers, and normal nonsmokers. In all groups, exercise induced a significant increase in the serum concentrations of all examined hormones. Increments were significantly higher in diabetic than in nondiabetic groups. No significant differences were observed between diabetic smokers and nonsmokers for all examined hormones. AVP responses during tests were similar in normal smokers and nonsmokers. In contrast, exercise-induced GH and cortisol increments were significantly lower in normal smokers than in normal nonsmokers.These data support the hypothesis that in normal subjects habitual nicotine consumption may attenuate both GH and cortisol responses to a releasing stimulation, such as physical exercise. This phenomenon may represent an expression of adaptation of nicotinic neurotransmission to chronic stimulation. Furthermore, the data show that the effect induced by habitual smoking is absent in diabetics, probably because of diabetes-induced neuroendocrine alterations in the central nervous system.

We have reported that melatonin exerts colony stimulating activity and rescues bone marrow cells from apoptosis induced either in vivo or in vitro by cancer chemotherapy compounds. We proposed that melatonin regulates interleukin-4 (IL-4) production in bone marrow T-helper cells and that IL-4 stimulates adherent stromal cells to produce colony stimulating factors (CSF). However, in further investigations we did not find any direct evidence of the ability of melatonin to stimulate IL4. We found that besides anti-IL4 monoclonal antibody (mAb), the opioid antagonist naltrexone also neutralized the colony stimulating activity and part of the hematopoietic protection exerted by melatonin. SDS-PAGE and immunoblotting analysis of supernatants of bone marrow T-helper cells incubated overnight with melatonin revealed the presence of two proteins with an apparent molecular weight of 15 and 67 kDa, which were recognized by both anti-common opioid sequence (Tyr-Gly-Gly-Phe) and anti-IL4 mAbs. When Abs against known opioid peptides were tested, only anti-dynorphin B Ab labeled the 67 kDa but not the 15 kDa protein. These melatonin-induced-opioids (MIO) were separated by gel filtration. The lower molecular weight MIO (MIO15) seems to mediate the naltrexone-sensitive hematopoietic effects of melatonin. Consistently, we found the presence of opioid receptors in adherent bone marrow cells. Apparently, the higher molecular weight protein, MIO67, was responsible for the naltrexone-insensitive part of the melatonin-induced hematopoietic rescue. These melatonin-induced T-helper cell products which resemble both IL-4 and dynorphin B might represent a new family of opioid peptides with hematopoietic and immune functions.

Short-term exposure of primary cultures of cerebellar granule cells from neonatal rat brain to high concentrations of glutamate resulted in a significant increase of both immunoreactivity to and mRNA levels of tau protein. Time-course experiments revealed the increases of tau immunoreactivity and mRNA levels to be maximal 2 h after the glutamate pulse. To investigate the relationship between newly synthesized tau protein and glutamate-induced neurotoxicity, neurons were preincubated with a specific tau antisense oligonucleotide. This treatment resulted in (i) inhibition of the glutamate-induced increase of tau immunoreactivity and (ii) a decrease in the sensitivity of the neurons to neurotoxic concentrations of glutamate. These data indicate that induction of the cytoskeleton-associated tau protein participates in the cascade of events promoted by glutamate leading to neurodegeneration.