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.

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.

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.

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.

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.

Clonal immunoglobulin gene rearrangements and normal T-cell receptor, bcl-2, and c-myc genes in primary cutaneous B-cell lymphomas.

Fourteen cases of primary cutaneous B-cell lymphomas were investigated at the immunohistochemical and molecular level to further characterize this newly defined entity. Neoplastic cells from all cases, phenotyped with a panel of monoclonal antibodies, were positive for HLA-DR, for the B-cell markers CD19, CD22, but not CD23 (except one case), and negative for the T-cell marker CD2. Monoclonal immunoglobulin light chains were demonstrated in six cases. The reactivity with the Ki-67 monoclonal antibody indicated that the neoplastic cells are proliferating. In five biopsies the presence of dendritic cells infiltrating the neoplastic areas was revealed using the monoclonal antibody Kim4b. By Southern blot analysis, clonal rearrangement of the immunoglobulin heavy chain gene (involving one or both alleles) was shown in 12 of 14 cases and of the light chain genes in 13 cases. The bcl-2 oncogene, normally involved in nodal follicular lymphomas, was in germ-line configuration. The c-myc and the beta and gamma chain genes of the T-cell receptor were also in the germ-line configuration. None of the cases presented Epstein-Barr virus sequences. These data indicate that primary cutaneous lymphomas of B-cell origin share morphological and phenotypic similarities with the nodal B-cell lymphomas of follicular histotype, are proliferating, and express in 45% of cases clear monoclonal immunoglobulin light chain; the molecular analysis confirms the B-cell derivation and the monoclonal nature of this neoplasia; it also shows that neither bcl-2 nor c-myc oncogenes are involved and that no inappropriate rearrangements of the T-cell receptor genes are found in this lymphoma.

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.

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.

Cognitive abnormalities and disease progression in a selected population of asymptomatic HIV-positive subjects.

A selected population of 41 homosexual/bisexual asymptomatic HIV-positive subjects were administered neurophysiological tests to assess language, memory, attention, logic faculties and visuo-motor functions. HIV-positive subjects differed from individually matched control subjects only in certain measures of verbal memory. Longitudinal evaluation performed after 1.5 years, however, did not indicate any further development of this mild amnesic deficit. Despite the small number studied in our sample, there seems to be a trend for older subjects to be at greater risk of developing AIDS and cognitive abnormalities than younger subjects, while differences in immunological status play a significant role in disease progression.

Collagen phagocytosis in multicentric reticulohistiocytosis.

A large number of dermal cells engaged in collagen phagocytosis were observed in a case of multicentric reticulohistiocytosis. These cells apparently start to engulf collagen by deep invaginations of the plasma membrane. Fusion of phagosomes containing the engulfed collagen with vesicles probably originating from the Golgi apparatus would give rise to secondary lysosomes. The process of collagen degradation leads to the appearance of fine fibrils and myelin bodies. The presence in the dermis of unusually thick collagen fibers might contribute to this process which appears to occur only under particular physiological and pathological conditions.

Primary cutaneous gamma/delta T-cell lymphoma presenting as disseminated pagetoid reticulosis.

The first case of primary gamma/delta cutaneous T-cell lymphoma (CTCL) with a fatal outcome is reported. The patient had the clinical and histopathologic features of disseminated pagetoid reticulosis, a rare form of CTCL characterized by a strong epidermotropic lymphoid infiltrate. Extensive immuno-cytochemical studies showed that the neoplastic cells were almost exclusively localized in the epidermis, expressed the gamma/delta variant of the T-cell receptor (CD3+, TCR-delta-1+) and were CD5+, CD7+, CD27+, CD29+, CD43+, CD44+, CD45+, CD45RA+, CD54+, CD69+, but beta F1-, Ti gamma a-, BB3-, A13-, CD2-, CD4-, CD8-, CD11a-, CD49d-, CD25-, CD30-, and HLA-DR-. A comparison of our results with those of the literature, which have not included gamma/delta T-cell receptor analysis, suggests that some reported cases of pagetoid reticulosis may have phenotypes similar to our case. Electron microscopy studies demonstrated that the gamma/delta T lymphocytes were villous, containing dense and multivesicular bodies, and formed close contacts with the surrounding keratinocytes, suggesting that these cells should have a role in the skin-associated lymphoid tissue. The proliferating cells in our case might represent the neoplastic counterpart of the recently reported CD2- subset of normal human peripheral blood gamma/delta T lymphocytes.

Synthesis and biological activities of 2-pyrimidinone nucleosides. 2. 5-Halo-2-pyrimidinone 2'-deoxyribonucleosides.

1-(2-Deoxy-beta-D-ribofuranosyl)-5-bromo-2-pyrimidinone (BrPdR) and 1-(2-deoxy-beta-D-ribofuranosyl)-5-iodo-2-pyrimidinone (IPdR) have been synthesized by condensation of the appropriate silylated bases 2a and 2b, respectively, with 3,5-bis-O-(p-chlorobenzoyl)-2-deoxy-alpha-D-ribofuranosyl chloride (8) in 1,2-dichloroethane, in the presence of SnCl4, followed by separation of the anomeric blocked nucleosides via column chromatography and subsequent deprotection with methanolic ammonia. Both BrPdR and IPdR exhibited significant antiherpes activities against various strains of HSV-1 and HSV-2, the latter compound (IPdR) showing the higher activity as well as the stronger binding to the virus-specific thymidine kinase.

Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen.

SUMMARY: Given the poor prognosis of patients with advanced cutaneous T-cell lymphoma and the high transplant-related mortality associated with conventional allogeneic bone marrow transplantation, we performed nonmyeloablative transplantation of allogeneic stem cells (ASCT) from HLA-identical siblings in three patients with this disease. All patients achieved full donor engraftment, clearance of clonal T cells leading to durable complete remissions but experienced high incidence of infections, which proved fatal in one case. These results suggest that nonmyeloablative ASCT is a novel and potentially curative therapy for patients with advanced T-cell lymphomas who have a histocompatible sibling.

Unusual cutaneous histiocytosis expressing an intermediate immunophenotype between Langerhans' cells and dermal macrophages.

Cutaneous histiocytosis was discovered in a 40-year-old man with a slow-growing nodule located on his right arm. Histologic findings showed an epidermotropic infiltrate of histiocytes with folded, irregular nuclei. Immunologically, the cells presented an intermediate phenotype between Langerhans' cells and dermal macrophages. After surgical removal of the lesion, neither a relapse nor visceral involvement was observed during two years of follow-up.

Generalized eruptive histiocytoma. A clinical, histologic, and ultrastructural study.

A case of adult self-healing histiocytosis, classified as generalized eruptive histiocytoma, is reported. Ultrastructural investigation of the cytoplasm of tumor cells revealed the presence of many dense and laminated bodies. The origin and possible importance of these bodies are described and discussed, and the need for quantitative study of cytoplasmic markers in histiocytic proliferations of the skin is emphasized.

5% Imiquimod cream for external anogenital warts in HIV-infected patients under HAART therapy.

The efficacy of imiquimod in the treatment of external genital warts in HIV positive subjects was compared to a group of patients with normal immune function. Imiquimod 5% cream was applied by patients three times a week until resolution for a maximum of 16 weeks. Assessment for response and the occurrence of side effects was performed every four weeks. Thirty-one per cent of 75 HIV positive patients achieved a complete clearance, a partial response was obtained in 24% of subjects while in 45% we observed no clinical response. In the control group a total clearance was obtained in 62% of subjects, a partial response in 24% and no response in 14%. Recurrences occurred in 4/23 HIV patients and 2/31 immunocompetent patients within three months of follow-up. Side effects were minor to moderate. We conclude that imiquimod 5% cream has an acceptable efficacy and safety on HIV patients.

Quality protein maize: a biochemical study of enzymes involved in lysine metabolism.

Quality protein maize (QPM) varieties have been produced by the introduction of opaque-2 modifier genes. Two QPM varieties, BR451 and BR473, a wild type and an opaque-2 variety, have been used to study key enzymes controlling lysine metabolism in the endosperm during development. Aspartate kinase and homoserine dehydrogenase enzymes, which are involved in lysine and threonine biosynthesis, respectively, exhibited identical activity patterns during endosperm development, with a maximum specific activity at 16 days after pollination. The QPM varieties exhibited higher levels of aspartate kinase activity in the endosperm, suggesting an increased rate of lysine biosynthesis when compared to the opaque-2 and wild-type genotypes. Similar results were observed for the lysine ketoglutarate reductase and saccharopine dehydrogenase enzymes, which form a single bifunctional polypetide involved in endosperm lysine degradation. Both enzyme activities were strongly reduced in the opaque-2 maize variety when compared to the wild-type maize, whereas the QPM varieties exhibited even lower levels of lysine ketoglutarate reductase-saccharopine dehydrogenase activities when compared to the opaque-2 variety. The developmental pattern of enzyme activity showed a different profile when compared to the enzymes involved in lysine biosynthesis, with activity being detected only 12-16 days after pollination (DAP) and maximum activities approximately 24 DAP. These results also suggest that the modifier genes have intensified the effect of the opaque-2 mutation on lysine ketoglutarate reductase-saccharopine dehydrogenase. These alterations lead to an increase in soluble lysine in the endosperm of the QPM varieties when compared to the opaque-2 and wild type.

Mycoplasma hominis and Ureaplasma urealyticum. Comparison of media for isolation and prevalence among patients with nongonococcal nonchlamydial genital infections.

One hundred and twelve genital specimens were cultured for Mycoplasma hominis and Ureaplasma urealyticum using a conventional system and the Mycotrim GU biphasic culture system. Both systems gave the same percentage of recovery (60%) of Mycoplasma hominis, while the recovery rates of Ureaplasma urealyticum were 95% with the conventional system and 83% with the Mycotrim GU. The media contamination was similar for both systems. The average time for Mycoplasma isolation and identification was shorter with the Mycotrim GU in comparison with the conventional system. The prevalence of Mycoplasma hominis in 91 patients with nongonococcal nonchlamydial urethritis and/or cervicitis was 8%, that of Ureaplasma urealyticum was 31%.