Pilot study of an arts- and theatre-based HIV prevention intervention for men who have sex with men and transgender women migrants in South Africa: acceptability, feasibility and preliminary efficacy.

Innovative approaches addressing the elevated human immunodeficiency virus (HIV) risk among men who have sex with men (MSM) or transgender women (TGW) migrants in South Africa are urgently needed. We sought to present the acceptability, feasibility and preliminary efficacy of 'Externalize and Mobilize!', a multi-session arts- and theatre-based HIV prevention group intervention for MSM and TGW migrants in South Africa. Fourteen participants-MSM (n = 7; 50%), genderqueer/nonbinary persons (n = 4; 29%) and TGW (n = 3; 21%)-in Cape Town were recruited and enrolled in the intervention and administered pre- and post-intervention assessments of HIV knowledge, HIV risk-reduction self-efficacy, stigma and resilience. The intervention, delivered over 4 days, was completed by all 14 participants. Scores on HIV knowledge and HIV risk-reduction self-efficacy were statistically significantly higher at post-intervention compared with pre-intervention. Additionally, participants responded affirmatively (i.e. 'Agree' or 'Strongly agree') on all items assessing intervention acceptability. Findings demonstrate the high acceptability, feasibility and preliminary efficacy of an arts- and theatre-based intervention for increasing HIV knowledge and HIV risk-reduction self-efficacy among MSM and TGW migrants in South Africa. This study provides further support for the use of creative and innovative interventions to address entrenched HIV disparities in South Africa.

The novel Mechanical Ventilator Milano for the COVID-19 pandemic.

This paper presents the Mechanical Ventilator Milano (MVM), a novel intensive therapy mechanical ventilator designed for rapid, large-scale, low-cost production for the COVID-19 pandemic. Free of moving mechanical parts and requiring only a source of compressed oxygen and medical air to operate, the MVM is designed to support the long-term invasive ventilation often required for COVID-19 patients and operates in pressure-regulated ventilation modes, which minimize the risk of furthering lung trauma. The MVM was extensively tested against ISO standards in the laboratory using a breathing simulator, with good agreement between input and measured breathing parameters and performing correctly in response to fault conditions and stability tests. The MVM has obtained Emergency Use Authorization by U.S. Food and Drug Administration (FDA) for use in healthcare settings during the COVID-19 pandemic and Health Canada Medical Device Authorization for Importation or Sale, under Interim Order for Use in Relation to COVID-19. Following these certifications, mass production is ongoing and distribution is under way in several countries. The MVM was designed, tested, prepared for certification, and mass produced in the space of a few months by a unique collaboration of respiratory healthcare professionals and experimental physicists, working with industrial partners, and is an excellent ventilator candidate for this pandemic anywhere in the world.

Advances in the FTU collective Thomson scattering system.

The new collective Thomson scattering diagnostic installed on the Frascati Tokamak Upgrade device started its first operations in 2014. The ongoing experiments investigate the presence of signals synchronous with rotating tearing mode islands, possibly due to parametric decay processes, and phenomena affecting electron cyclotron beam absorption or scattering measurements. The radiometric system, diagnostic layout, and data acquisition system were improved accordingly. The present status and near-term developments of the diagnostic are presented.

Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss.

BACKGROUND AND AIMS: We investigated the effect of different exercise modalities on high sensitivity-C reactive protein (hs-CRP) and other inflammatory markers in patients with type 2 diabetes and the metabolic syndrome. METHODS AND RESULTS: Eighty-two patients were randomized into 4 groups: sedentary control (A); receiving counseling to perform low-intensity physical activity (B); performing prescribed and supervised high-intensity aerobic (C) or aerobic+resistance (D) exercise (with the same caloric expenditure) for 12 months. Evaluation of leisure-time physical activity and assessment of physical fitness, cardiovascular risk factors and inflammatory biomarkers was performed at baseline and every 3 months. Volume of physical activity increased and HbA(1c) decreased in Groups B-D. VO(2max), HOMA-IR index, HDL-cholesterol, waist circumference and albuminuria improved in Groups C and D, whereas strength and flexibility improved only in Group D. Levels of hs-CRP decreased in all three exercising groups, but the reduction was significant only in Groups C and D, and particularly in Group D. Changes in VO(2max) and the exercise modalities were strong predictors of hs-CRP reduction, independent of body weight. Leptin, resistin and interleukin-6 decreased, whereas adiponectin increased in Groups C and D. Interleukin-1ß, tumor necrosis factor-α and interferon-γ decreased, whereas anti-inflammatory interleukin-4 and 10 increased only in Group D. CONCLUSION: Physical exercise in type 2 diabetic patients with the metabolic syndrome is associated with a significant reduction of hs-CRP and other inflammatory and insulin resistance biomarkers, independent of weight loss. Long-term high-intensity (preferably mixed) training, in addition to daytime physical activity, is required to obtain a significant anti-inflammatory effect.

Self glucose monitoring and physical exercise in diabetes.

Cardiorespiratory fitness, which is determined mainly by the level of physical activity, is inversely related to mortality in the general population as well as in subjects with diabetes, the incidence of which is also increased by low exercise capacity. Exercise is capable of promoting glucose utilization in normal subjects as well as in insulin-deficient or insulin-resistant diabetic individuals. In diabetic subjects treated with insulin or insulin secretagogues, exercise may also result in complications, with too much insulin causing hypoglycaemia and not enough insulin leading to hyperglycaemia and possibly ketoacidosis; both complications may also occur several hours after exercise. Therefore, self-monitoring of blood glucose before, during (for exercise duration of more than 1 h) and after physical exercise is highly recommended, and also carbohydrate supplementation may be required. In the Italian Diabetes Exercise Study (IDES), measurement of blood glucose and systolic and diastolic blood pressure levels before and after supervised sessions of combined (aerobic + resistance) exercise in type 2 diabetic subjects with the metabolic syndrome showed significant reductions of these parameters, though no major hypoglycaemic or hypotensive episode was detected. The extent of reduction of blood glucose was related to baseline values but not to energy expenditure and was higher in subjects treated with insulin than in those on diet or oral hypoglycaemic agents (OHA). Thus, supervised exercise training associated with blood glucose monitoring is an effective and safe intervention to decrease blood glucose levels in type 2 diabetic subjects.

Ano-rectal lymphogranuloma venereum: the first case in Italy.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection endemic in Central Africa, South-East Asia and in some countries of Central and South America. In Italy LGV has been sporadically reported in patients coming from abroad. The etiological agent of LGV is Chlamydia trachomatis serovars L1, L2, L3, differentiating by pathogenetic action. The clinical course of LGV can be divided into three stages with a initial small papule, which may ulcerate, at the site of inoculation, followed by massive lymphadenopathy, which is usually unilateral, and eventually by lymphatic obstruction, causing elephantiasis. During 2004 a LGV ano-rectal clinical variant has been described as an erosive proctitis among homosexual HIV-positive men in some countries of Western Europe, not coming from endemic areas. Until now this syndrome has been often explained as chronic intestinal inflammatory disease. This report describes a case of proctitis caused by CT serovar L2; to Authors' knowledge this is the first case reported in Italy.

Menopause modulates homocysteine levels in diabetic and non-diabetic women.

High total homocysteine (tHcy) plasma levels may contribute to the increased cardiovascular risk of Type 2 diabetic women. However, to date, data on factors modulating tHcy concentration in this population are scarce. Fasting tHcy, vitamin B12, folate plasma levels, and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype as well as clinical, biochemical, and lifestyle variables were compared in 91 Type 2 diabetic and 91 matched non-diabetic women (40 pre- and 51 post-menopausal, in each group). Fasting tHcy concentration did not differ between diabetic and control women, even after multivariable adjustment. In both groups, tHcy levels increased after menopause, but the differences were weakened after multivariable adjustment. The MTHFR genotype distribution was in accordance with the Hardy-Weinberg equilibrium, with a similar TT frequency in diabetic (22.2 %) and control women (19.8%). Overall, tHcy plasma concentration was higher in TT homozygous compared to other genotypes. We found a menopause-genotype interaction on tHcy levels (p=0.068 for menopause*genotype interaction); overall, the increase of tHcy concentration in TT subjects was limited to pre-menopause (p<0.0001; adjusted p=0.024), and this was confirmed after considering diabetic and control women separately (p=0.001 and p=0.01, respectively). At multivariate analysis, menopause was an independent correlate of tHcy concentration, together with creatinine, folate and MTHFR genotype. Our data show that menopause has a strong influence on tHcy concentration even in Type 2 diabetic women and demonstrate, for the first time, that it may modulate the association between tHcy and the common MTHFR polymorphism both in diabetic and non-diabetic women.

Leflunomide-induced subacute cutaneous lupus erythematosus with erythema multiforme-like lesions.

Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-alpha-induced cellular responses. A number of leflunomide-related adverse events have been reported. Among cutaneous side effects, a few cases of subacute cutaneous lupus erythematosus have been described. We report a previously undocumented reaction to leflunomide, manifesting as subacute cutaneous lupus erythematosus and erythema multiforme-like lesions, in a young woman treated with this drug for ankylosing spondylitis. Withdrawal of leflunomide combined with a short cycle of systemic corticosteroid led to the resolution of the patient's rash, indicating this drug as being responsible for the development of the disease. We conclude that leflunomide might have triggered the occurrence of both subacute cutaneous lupus erythematosus and erythema multiforme in a patient with pre-existing autoimmune diathesis. The suppressive effect of this drug on tumor necrosis factor-alpha-related mechanisms might have played a role in the induction of such a unique reaction to leflunomide.

Widespread idiopathic pyoderma gangrenosum evolved from ulcerative to vegetative type: a 10-year history with a recent response to infliximab.

Pyoderma gangrenosum (PG) is an infrequent neutrophilic dermatosis, which commonly presents with a limited number of ulcerative, pustular, bullous or vegetative lesions associated with an underlying systemic disorder. We report a 34-year-old man with ulcerative PG that was exceptionally widespread and not associated with any other condition. Moreover, it was resistant to steroid treatment and, after prolonged use of ciclosporin, it unexpectedly developed a vegetative pattern, further supporting the hypothesis that the different forms of PG are part of a single clinical spectrum. Finally, dramatic improvement of the condition occurred after treatment with infliximab, an antitumour necrosis factor-alpha monoclonal antibody; however, this produced circulating autoantibodies. Although this has not had any clinical consequence to date, accurate follow-up in patients treated with infliximab is essential to monitor the onset of a possible autoimmune disorder induced by the drug.

Mild hyperhomocysteinemia and the common C677T polymorphism of methylene tetrahydrofolate reductase gene are not associated with the metabolic syndrome in Type 2 diabetes.

A moderate increase of total homocysteine (tHcy) plasma levels seems to increase cardiovascular disease (CVD) risk in Type 2 diabetic subjects, but its relationship with diabetes and insulin-resistance is still controversial. We examined whether mild hyperhomocysteinemia and its major genetic determinant would cluster with the metabolic syndrome (MS) in Type 2 diabetes. One hundred Type 2 diabetic subjects with and without MS were enrolled in the study. Fasting tHcy, vitamin B12, and folate plasma levels, insulin-resistance [assessed by homeostasis model assessment, (HOMAIR)] and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype were assessed in all the participants. Geometric mean tHcy concentration and the prevalence of mild hyperhomocysteinemia, as commonly defined by tHcy >/=15 micromol/l, were comparable in diabetic subjects with and without MS, even after adjustment for age, sex, vitamin B12, folate and creatinine levels. In both groups, the MTHFR C677T genotype distribution was not significantly different from the Hardy-Weinberg equilibrium, with a TT homozygous frequency of 21% in subjects with and 18% in those without the syndrome (p=ns). tHcy plasma levels and the degree of insulin-resistance did not differ across MTHFR genotypes in both groups, even after multivariable adjustment. Overall, tHcy significantly correlated with creatinine (r=0.25; p=0.009) and trygliceride concentrations (r=0.24; p=0.02), but not with HOMAIR. At multivariate analysis, only creatinine was significantly correlated with tHcy levels (beta=0.42; p=0.001). In conclusion, hyperhomocysteinemia and the common C677T variant of MTHFR gene are not associated with MS in Type 2 diabetic subjects.

Early genomics of learning and memory: a review.

The characterization of the molecular mechanisms whereby our brain codes, stores and retrieves memories remains a fundamental puzzle in neuroscience. Despite the knowledge that memory storage involves gene induction, the identification and characterization of the effector genes has remained elusive. The completion of the Human Genome Project and a variety of new technologies are revolutionizing the way these mechanisms can be explored. This review will examine how a genomic approach can be used to dissect and analyze the complex dynamic interactions involved in gene regulation during learning and memory. This innovative approach is providing information on a new class of genes associated with learning and memory in health and disease and is elucidating new molecular targets and pathways whose pharmacological modulation may allow new therapeutic approaches for improving cognition.

Cutaneous granulomatous reaction to injectable hyaluronic acid gel.

Injectable hyaluronic acid (HA) derivatives are the most used reabsorbable dermal fillers for soft tissue augmentation today and their utilization is considered safe. We report a cutaneous granulomatous reaction that developed in a woman 5 weeks after the first treatment with a nonanimal HA derivative for the correction of facial wrinkling. We describe the clinicopathological findings and course of the cutaneous reaction. The adverse reaction showed clinical and histopathological characteristics comparable to the few previously reported cases. All cutaneous lesions spontaneously disappeared without scars within 3 months. We conclude that even nonanimal injectable HA derivatives can be associated with delayed granulomatous reactions. The patient should be informed of this potential long-term complication.

The usefulness of clonality for the detection of cases clinically and/or histopathologically not recognized as cutaneous T-cell lymphoma.

BACKGROUND: The determination of clonality has proven to be a useful adjunct to the diagnosis of cutaneous lymphocytic infiltrates. It is considered particularly helpful for the distinction of mycosis fungoides (MF) and inflammatory dermatoses. OBJECTIVES: To verify the sensitivity of the polymerase chain reaction (PCR)-heteroduplex analysis of T-cell receptor gamma-chain gene (TCRgamma) rearrangements in patients with MF and to establish whether a clinicopathological re-evaluation of lesions previously unclassified or considered to be non-neoplastic entities but found to be monoclonal allowed the recognition of additional cases of MF. METHODS: Included in the study were 116 patients, seen at our Institute from April 2002 to September 2003 and tested for TCRgamma rearrangements. Thirty-six patients were affected by clinically and histopathologically proven MF, while the remaining 80 cases had not been classified or had been classified as non-neoplastic entities. The sensitivity of the molecular analysis was determined on the basis of the results obtained in the 36 patients with MF. The 29 cases of the second series of patients found to be monoclonal were clinically and histopathologically re-evaluated. RESULTS: Clonal rearrangements were found in 87.5% of patients with plaque stage MF and in 20% of those with patch stage MF. The clinicopathological re-evaluation allowed us to reclassify 15 of 29 monoclonal cases of the second series of patients as MF. CONCLUSIONS: The study showed that the PCR-heteroduplex technique can determine a high percentage of monoclonality only in plaque stage MF. However, in spite of the low sensitivity of the method, several cases previously unrecognized could be reclassified as MF when their clinical and histopathological features were re-evaluated taking into account the clonality of the lymphocytic infiltrate.

Sclerodermic linear lupus panniculitis: report of two cases.

Lupus erythematosus panniculitis is a rare disease characterized by deep subcutaneous nodules, most commonly localized on the upper limbs and face. Unique clinical presentations, such as linear configuration or 'overlap' forms between lupus erythematosus panniculitis and localized scleroderma have been reported. We present here the clinical characteristics, course and laboratory findings of 2 patients having linear lupus erythematosus panniculitis with localized scleroderma-like changes. The 2 patients (of the 14 patients with lupus erythematosus panniculitis seen by us since 1990) were females with a young age at the onset of disease (median, 25 years). In 1 case, evolution into systemic lupus erythematosus with severe renal involvement occurred whereas the other patient, who had a spontaneous abortion and exhibited anticardiolipin antibodies, should be followed and screened for the emergence of antiphospholipid syndrome. Thus, the clinical behavior of this variant seems to be more aggressive, as compared with the usual course of lupus erythematosus panniculitis, which is considered to be a benign disease, although some reports have suggested that its prognosis is not always favorable. The linear distribution could be the clinical hallmark of such a unique, 'sclerodermic' subset of lupus erythematosus panniculitis.

Adding semantics to gene expression profiles: new tools for drug discovery.

Gene expression profiles are unveiling a wealth of new potential drug targets for a wide range of diseases, offering new opportunities for drug discoveries. The emerging challenge, however, is the effective selection of the myriad of targets to identify those with the most therapeutic utility. Numerical clustering has became a commonly used method to investigate and interpret gene expression data sets but it is often inadequate to infer the genes' and proteins' role and point to candidate genes for drug development. This review illustrates how clustering methods based on semantic characteristics, such as gene ontologies, could be used to extract more knowledge from genomic data and improve drug target and discovery processes.

Inflammatory markers in women with a recent history of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a risk factor for both Type 2 diabetes (DM2) and insulin-resistance syndrome (IRS). C-reactive protein (CRP), fibrinogen and leukocyte count are increased in the IRS and predict DM2 and cardiovascular disease (CVD). The chemochine monocyte chemoattractant protein-1 (MCP-1/CCL2) is also elevated in DM2 and CVD. Recent evidence suggests a relation between chronic inflammation and GDM, but post-delivery information on inflammatory markers in these high-risk women is lacking. Serum levels of CRP, fibrinogen, MCP-1/ CCL2, and leukocyte blood count have been assessed in 26 women with and 26 women without a recent history of GDM, matched for age, body mass index (BMI), post-partum duration and parity. DM2 was excluded in all the participants by an oral glucose tolerance test (OGTT). Women with previous GDM showed significantly higher CRP (p=0.007) and fibrinogen (p=0.02) serum concentrations, whereas MCP-1/CCL2 serum levels and leukocyte blood count were comparable in the two groups. Overall, CRP levels significantly correlated with BMI (r=0.40, p=0.03), waist-to-hip ratio (WHR) (r=0.44, p=0.001), fasting insulin (r=0.27, p=0.04), insulin-resistance assessed by means of the homeostatic model (HOMA) (r=0.28, p=0.04), and fibrinogen concentration (r=0.49, p=0.0001). At linear regression analysis, only WHR and fibrinogen were independently associated with CRP levels. In conclusion, the increase of inflammatory markers may be one of the first detectable disorders in healthy women at high risk of DM2 and IRS, like those with a GDM history.

Keratosis lichenoides chronica and eruptive keratoacanthoma-like lesions in a patient with multiple myeloma.

We describe a 72-year-old woman with a 13-year history of a lichenoid dermatitis, who developed multiple, papular keratoacanthoma (KA)-like lesions and few crater-like nodules on the extremities over a period of 6 months before our observation. Her medical history also recorded multiple myeloma diagnosed a few years before. The long-standing dermatosis was diagnosed, clinically, as keratosis lichenoides chronica (KLC), although, histologically, a lichenoid tissue reaction pattern was not evident. On the other hand, histology from papular and nodular lesions of recent onset was consistent with a possible early phase of KA and spinocellular carcinoma, respectively. Oral acitretin induced regression of KA-like lesions and improvement of KLC but had no effects on crater-like nodules, which required surgical excision. KLC is a chronic disorder of keratinization characterized by lichenoid hyperkeratotic papules arranged in a linear pattern, erythematosquamous plaques and seborrhoea-like dermatitis. We emphasize in our case the association between KLC and multiple possible KAs, never previously reported, and speculate that these two rare conditions may represent here a 'continuum' from a pathogenetic point of view.

Elephantoid oedema of the eyelids.

We describe a male patient with rosacea who had a 2-year history of persistent bilateral oedema of the eyelids, leading to an elephantoid condition with blepharoptosis. An upper eyelid blepharoplasty was performed, but swelling progressively recurred over a few months. Based on the case history, clinical appearance and histological findings, rosaceous lymphoedema was considered to be the diagnosis. The latter is a bilateral, solid oedema of the mid-third of the face, regarded as a rare complication of rosacea. It is thought to occur as a result of chronic inflammation and lymphatic stasis, but its exact aethiopathogenesis remains elusive. Predominant eyelid involvement, causing severe visual impairment as in our patient, is unique.