Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Mass screening for hepatitis B and C viruses in a population of persons with disabilities with and without HIV status in Cameroon.

Hepatitis viral infections are one of major threat to public health worldwide. The vast majority of people infected with viral hepatitis are found in resources limited countries of Africa and Asia. There is a lack of accurate data to better determine the burden of this disease in Cameroon, moreover among vulnerable people. The aim of this study was to estimate the seroprevalence of HBV and HCV viruses among persons with disabilities (PwD) with or without HIV status.

Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects.

We investigated the early effects of whole body vibration (WBV) added to hypocaloric diet on insulin-resistance and other parameters associated with glucose regulation in sedentary obese individuals. We randomly assigned 34 patients to WBV plus hypocaloric diet (WBV group) or diet alone (CON group) for 8 weeks. Fasting and post-load glucose, insulin, lipids, C-reactive protein, tumor necrosis factor-α, leptin, adiponectin were assessed. Insulin sensitivity index (ISI) was derived from oral-glucose-tolerance test. Body composition was evaluated with dual-energy X-ray absorptiometry. Both groups lost approximately 5% of weight, with greater reduction of body fat in WBV than in CON (-7.1±1.2 Kg vs. -5.3±1.0 Kg, p=0.003). Percent variation of ISI was more pronounced in WBV than in CON group (+35±4% vs. + 22±5%, p=0.002), accompanied by slight improvement in post-load glucose (-1.07±0.02 vs. - 0.12±0.01 mmol/l, p=0.031) but without changes in fasting levels. Adiponectin significantly increased in WBV group compared with CON (p=0.021 for comparison) whereas no differences in leptin and inflammatory markers were observed. In middle-aged sedentary obese subjects, WBV added to hypocaloric diet for 8 weeks improved body composition, insulin-resistance, glucose regulation and adiponectin levels to a greater extent compared with diet alone. Efficacy and feasibility of this approach in the long term need to be ascertained.

Increased frequency of immunoglobulin (Ig)A-secreting cells following Toll-like receptor (TLR)-9 engagement in patients with Kawasaki disease.

Kawasaki disease (KD) is an acute vasculitis affecting mainly infants and children. Human B cells express Toll-like receptor (TLR)-9, whose natural ligands are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of bacterial DNA. The aim of this study was to clarify the pathogenesis of KD analysing the activation status of peripheral blood mononuclear cells (PBMC), focusing on B lymphocyte activation and functions. Ten patients and 10 age-matched healthy donors were recruited from the Bambino Gesù Hospital of Rome, Italy and enrolled into this study. We determined phenotype profile and immunoglobulin (Ig) production of PBMC from KD patients and age-matched controls. We found that the frequency of CD19(+) B lymphocytes and CD19(+) /CD86(+) activated B lymphocytes from KD patients during the acute phase before therapy was increased significantly. Moreover, B lymphocytes of acute-phase KD patients were more prone to CpG oligodeoxynucleotide (ODN) activation compared with the age-matched controls, as assessed by a significant increase of the number of IgA-secreting cells (SC). In the same patients we found a marked increase of IgM, IgG, interleukin (IL)-6 and tumour necrosis factor (TNF)-α production compared with the control group. In addition, in two convalescent KD patients, conventional treatment with intravenous immunoglobulin (IVIG) restored the normal frequency of CD19(+) B cells, the number of IgA-, IgM- and IgG-SC and the production of IL-6 and TNF-α. Our findings indicate that the percentages of peripheral B lymphocytes of acute-phase KD patients are increased and are prone to bacterial activation in terms of increased numbers of IgA-SC and increased production of IL-6 and TNF-α inflammatory cytokines. Thus, our data support the hypothesis of an infectious triggering in KD.

17beta-Hydroxysteroid dehydrogenase-3 deficiency: from pregnancy to adolescence.

OBJECTIVE: Aim of this study is to report on basal clinical phenotype and follow up after diagnosis, of patients with 17beta-hydroxysteroid-dehydrogenase type 3 (17beta-HSD3) deficiency in Italy. SETTING: Pediatric Endocrine Departments, University Hospitals. PATIENTS: The cases of 5 Italian subjects affected by 17beta-HSD3 deficiency are presented in this study. INTERVENTIONS: Laboratory and genetic assessment. Gonadectomy and female sex assignment (4 patients) or GnRH analog therapy to regress puberty and gender identity disorder (1 patient). RESULTS: Presentation lasted from pregnancy (pre-natal diagnosis of a 46,XY fetus with female external genitalia) to infancy (inguinal hernia containing testes/clitoromegaly) and adolescence (virilisation). All subjects but one (subject 1, Central-Northern Italy) were from small areas of Southern Italy. Endocrine data (baseline and/or stimulated testosterone/ Delta4-androstenedione ratio) were informative. Two girls were homozygous for 17beta-HSD3 gene mutations (G289S/G289S; R80W/R80W), while the others were compound heterozygous (IVS325+4 A>T/A203V; L212Q/M235V; R80W/A235E). Four patients were confirmed as females and were well-adjusted with assigned sex; gender identity disorder improved during treatment with GnRH analog in the last subject. CONCLUSIONS: 17betaHSD3 deficiency may present from pregnancy to puberty for different clinical issues. Albeit testosterone/Delta4-androstenedione ratio represents the most accurate endocrine marker to diagnose the disorder, hCGstimulation is mandatory in pre-puberty. Molecular analysis of 17beta-HSD3 gene should be performed to confirm the diagnosis. Temporary GnRH analog treatment may regress gender identity disorder and provide time to confirm or change the birth sex assignment. Female individuals seems to be compliant with their sex, providing that virilisation does not occur. In Italy, the disorder seems to be more prevalent in the Southern regions and shows genetic heterogeneity.

Clinical, endocrine, and molecular findings in 17beta-hydroxysteroid dehydrogenase type 3 deficiency.

The 17beta-hydroxysteroid dehydrogenases (17betaHSD) gene family comprises different enzymes involved in the biosynthesis of active steroid hormones. The 17betaHSD type 3 (17betaHSD3) isoenzyme catalyzes the reductive conversion of the inactive C19-steroid, Delta4-androstenedione (Delta4- A), into the biologically active androgen, testosterone (T), in the Leydig cells of the testis. It is encoded by the 17beta-hydroxysteroid dehydrogenase type 3 (HSD17B3) gene, which maps to chromosome 9q22. Mutations in the HSD17B3 gene are associated with a rare form of 46,XY disorder of sex development referred to as 17betaHSD3 deficiency (or as 17-ketosteroid reductase deficiency), due to impaired testicular conversion of Delta4-A into T. 46,XY patients with 17betaHSD3 deficiency are usually classified as female at birth, raised as such, but develop secondary male features at puberty. Diagnosis, and consequently early treatment, is difficult because clinical signs from birth until puberty may be mild or absent. Biochemical diagnosis of 17betaHSD3 deficiency requires measurement of serum T/Delta4-A ratio after hCG stimulation test in pre-pubertal subjects, while baseline values seem to be informative in early infancy and adolescence. However, low basal T/Delta4-A ratio is not specific for 17betaHSD3 deficiency, being sometimes also found in patients with other defects in T synthesis or with Leydig cells hypoplasia. Mutational analysis of the 17HSDB3 gene is useful in confirming the clinical diagnosis of 17betaHSD3 deficiency. This review describes clinical findings, diagnosis, and molecular basis of this rare disease.

Induction of antibody forming cells with specificity for Candida albicans mannoproteins in cultures of human peripheral blood lymphocytes.

A method is described for the induction of a specific antibody response to Candida albicans in cultures of normal human peripheral blood lymphocytes (PBL). PBL were cultured in the presence of whole C. albicans cells and the antibody response was evaluated by the ELISPOT technique, on plastic wells coated with a purified candidal cell well mannoprotein (MP). Under the conditions described here, a specific antibody response was obtained in all of the eight donors tested. The response was antigen-dependent and antigen-specific, peaked around day 10-12 of culture and the antibodies belonged to both the IgM and the IgG isotypes. By testing the cultured cells on MP from different Candida species, the method permitted the detection of antibodies directed against MP epitopes shared by C. albicans and C. parapsilosis.

The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope.

Synthetic peptides containing amino acid sequence 218-238 of the core protein p24 of human immunodeficiency virus type 1 (HIV-1) and progressively shorter sequences at its C-terminus, were tested for their effect on antigen dependent in vitro responses of peripheral blood lymphocytes (PBL) from normal human donors. A peptide as short as 7 amino acids, corresponding to a highly conserved sequence, was able to inhibit in a dose-dependent manner the induction of a specific primary antibody response to the sheep red cell (SRC) antigen, as well as the proliferative response to recall microbial antigens. The results of this study constitute additional evidence of the immunoinhibitory effects of HIV components and may help to unravel some of the pathogenic mechanisms of AIDS. Moreover, they are of potential relevance for the development of immunoprophylactic and therapeutic strategies.

Interstitial and large chromosome 1p deletion occurs in localized and disseminated neuroblastomas and predicts an unfavourable outcome.

We studied chromosome 1p loss of heterozygosity (1p-LOH) in 53 neuroblastomas (NBs) using 15 (CA)n repeat loci, which covered a region of 90 cM. We also assessed chromosome 1p36 deletion by fluorescence in situ hybridization (FISH) on interphase nuclei. 1p-LOH was found in 19 (36%, 95% confidence interval (CI) 23-50%) NBs. We detected interstitial and large deletion in both localized and disseminated tumours and in one tumour of a patient at stage 4S. Allelic loss was frequently observed in 1p36 and 1p32 regions. In patients older than 1 year of age (53 versus 13%, P < 0.002) we detected significant chromosome 1p deletion and it was associated with MYCN amplification (P = 0.001). Overall survival (OS) analysis showed that 1p-LOH is predictive of a poor outcome (odds ratio 16.5, 95% CI 5.4-50.9%); therefore, 1p-LOH should be regarded as an additional tumour progression marker in neuroblastoma.

Neuroblastoma in two siblings supports the role of 1p36 deletion in tumor development.

Familial neuroblastoma occurs rarely. We studied a family with three children; one of them has a disseminated (stage 4) and another has a localized (stage 2) neuroblastoma. We observed subtelomeric locus D1Z2 (1p36) deletion in both tumors by using double-color fluorescence in situ hybridization. The MYNC gene was found in single copy in both tumors. Loss of heterozygosity (LOH) and restriction fragment length polymorphism analyses were performed by using DNA from frozen tumor cells and from microdissected tumor areas excised from paraffin-embedded sections. We detected somatic LOH at locus D1S468 (1p36) in a tumor-cell population with a trisomy 1 of the stage-2 patient. Neuroblastoma cells of the stage-4 patient were diploid and showed allelic loss at the following loci: D1S172, D1S80, D1S94, D1S243, D1S468, D1S214, D1S241, and D1S164. Haplotype study showed that the siblings inherited the same paternal 1p36-->pter chromosome region by homologous recombination and that, in the two tumors, arm 1p of different chromosomes of maternal origin was damaged. Our results suggest that the siblings inherited the predisposition to neuroblastoma associated with paternal 1p36 region and that tumors developed as a consequence of somatic loss of the maternal 1p36 allele.

A mannoprotein constituent of Candida albicans cooperates with antigen in the induction of a specific primary antibody response in cultures of human lymphocytes.

The effects of Candida albicans mannoproteins on the induction of a primary antibody response to a T-dependent antigen, sheep erythrocytes (SRBC), in cultures of human blood lymphocytes, were investigated. Two experimental systems (bulk and limiting dilution cultures) allowing the detection of both enhancing and inhibitory effects, were used. In bulk cultures, antigen alone elicited a small number of specific antibody forming cells, unless IL-2 was supplied. Addition of the fungal mannoprotein extract or of a purified constituent of it increased 5 to more than 10 times the specific response. When limiting dilution analysis was performed, we observed that: a) a similar number of specific precursor cells was induced by antigen and either IL-2 or mannoprotein; b) the plot of the number of seeded cells versus the log of the fraction of negative cultures was linear in antigen and IL-2 triggered cultures but constantly deviated from linearity when the candidal stimulant was added. Thus, more than one type of precursor cell was limiting in these cultures, and the immunoenhancing effect of mannoprotein may involve multiple cellular interactions.

Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV.

The effect of a synthetic peptide, corresponding to a sequence of HIV-1 p24 protein (amino acids 218-237), on in vitro immune responses was studied. The peptide inhibited in a dose-dependent manner the induction of an anti-SRC antibody response and of a PPD-specific proliferative response of human PBL. On the other hand, PHA-induced proliferation of human PBL and PPD-induced proliferation of a PPD-specific human T-cell line were not modified by comparable amounts of the peptide. These results suggest that structures from a protein (p24), present in the serum throughout the course of HIV infection, are able to interfere with the inductive stages of specific immune responses. These findings may help to unravel some of the pathogenic mechanisms of AIDS and may contribute to the development of vaccine strategies.

[Pain and pancreaticojejunostomy. Considerations on surgical anatomy and physiopathology]. / Dolore e pancreatico-digiunostomia. Considerazioni di anatomia chirurgica e fisiopatologia.

The Authors report the case of a patient who, following a side-to-side Wirsung-jejunostomy for chronic pancreatitis, became symptomatic again for anastomotic obstruction and progression of the pancreatic disease. Results of pancreaticojejunostomy are compared to those reported by other Authors. Controversies on pathophysiology, diagnosis, and therapy are analyzed as well.

Muscle-specific microRNAs as biomarkers of Duchenne Muscular Dystrophy progression and response to therapies.

Recent studies have revealed the contribution of fibro-adipogenic progenitors (FAPs) to the pathogenesis and progression of Duchenne Muscular Dystrophy (DMD). While FAPs direct compensatory regeneration at early stages of disease, as the disease progresses they contribute to the progressive replacement of contractile myofibers with fibrotic scars and fatty infiltration. Using the mouse model of DMD - the mdx mice - we have recently reported that FAPs mediate the ability of HDAC inhibitors (HDACi) to promote muscle regeneration and prevent fibro-adipogenic degeneration at early stages of disease. This effect is mediated by the induction of myomiRs that, in turn, target the SWI/SNF components BAF60A and B, thereby favoring the formation of BAF60C-based SWI/SNF complex, which directs the switch from the fibro-adipogenic to the myogenic lineage. Here we show direct evidence of induction of miR-206 and BAF60C, and reduction of BAF60A, in FAPs isolated from mdx muscles exposed to the HDACi Trichostatin A (TSA). We also discuss how increased expression of myomiRs in dystrophic muscles can be integrated with circulating myomiRs to provide accurate biomarkers of disease progression and response to treatment.

IFN-alpha amplifies human naive B cell TLR-9-mediated activation and Ig production.

TLRs are a family of molecules that function as sensors for the detection of pathogens. TLR-9, expressed on B cells and pDCs, recognizes CpG motifs of unmethylated bacterial DNA and plays a role in the development of autoimmunity. The present study was designed to investigate the effects of IFN-alpha in combination with CpG ODN on the activation of CD27(-) naïve B cells and on Ig production. We provide evidence that CpG ODN not only induces a total and T-dependent, specific IgM response by naïve B cells but also their phenotypic differentiation in plasma cells, as demonstrated by the up-regulation of CD38 expression. We found that TLR-9 stimulation with CpG ODN induces IL-1beta, TNF-alpha, IL-10, and IL-6 production. Interestingly, we also found that CpG ODN induces naïve B cell maturation into memory cells, as demonstrated by the induction of CD27, AID mRNA expression, and IgG production. More importantly, our results demonstrate that IFN-alpha amplifies the inductive effect of CpG ODN on naïve B activation and on Ig production through a mechanism involving TLR-9/MyD88-dependent signaling. Moreover, we found that IFN-alpha enhances the frequency of CpG ODN-induced memory B cells. Our results may contribute to clarify the events promoting IFN-alpha-induced amplification of naïve B cell activation via TLR-9 for a better understanding of the pathogenesis of autoimmune disorders and may guide treatments targeting this pathway within B cells.

[Dynamic psychopathology of anorexia nervosa. Clinical hypothesis]. / Psicopatologia dinamica dell'anoressia nervosa. Un'ipotesi clinica.

In this paper the Authors discuss the psychopathological problem of nervous anorexia. Moving from a psychodynamic point of view, they examine the anorexic defensive strategy and the psycho-pathogenetic aspects which are probably involved in its expression.

HIV-1 Nef protein inhibits the in vitro induction of a specific antibody response to Candida albicans by an early up-regulation of IL-15 production.

We have previously demonstrated that exogenous Nef protein induced activation of normal human T cells up-regulating IL-15 production by monocytes. Since HIV-1 infection results in the early impairment of immune functions we decided to evaluate if Nef is able to modulate the induction of a specific antibody response. Human peripheral blood mononuclear cells from healthy donors were induced in vitro to mount a specific antibody response to the Candida albicans antigen. We show that Nef inhibited, in a dose-dependent manner, the induction of the anti-C. albicans antibody response. The ability of an anti-Nef antibody to prevent such inhibition indicates that the effect was indeed Nef-specific. In the Nef-treated cultures an early increase of IL-15 production was observed and the addition of anti-IL-15 antibody abrogated the Nef-induced inhibitory effect. Moreover the addition of IL-15 to the cultures inhibited, as well as Nef, the induction of the specific antibody response. Thus, our results suggest that Nef may inhibit the induction of a specific antibody response by an early up-regulation of IL-15 production. A better comprehension of this phenomenon may be important for unravelling some aspects of the B cell defects in HIV infection.

[Clinical consistency in the diagnostic approach to the patient. Notes relating to the use of psychometric procedures in clinical psychiatry]. / Coerenza clinica nell'approccio diagnostico al paziente. Alcune note relative alla utilizzazione delle procedure psicometriche in psichiatria clinica.

The authors underline the difficulties of the introduction and use of the psychometric approach in psychiatry. The use of protocols for the standardised evaluation and measurement of psychopathological phenomena is soon revealed to be open to criticism regarding the objective character of the object of the inquiry in psychiatry; at the same time there is an equally legitimate need not only for "forms" but also clinical "contents" without which the doctor's role loses its traditional target.

[Pharmacological treatment of delusional depression]. / La terapia farmacologica della depressione psicotica.

Delusional depression is characterised by the presence of symptoms such as hallucinations (typically auditory) and delusions either mood congruent and incongruent. Most commonly the content of delusions is consistent with the depressive themes: guilt, unworthlessness, poverty, death. Hallucinations, when present, are not elaborate and may involve voices that berate the patient for shortcomings or sins. Mood incongruent psychotic symptoms include persecutory delusions, delusions of thought insertion or thought broadcasting. Several pharmacological studies have demonstrated a differential response pattern in delusional depression and in nondelusional depression. Delusional depressives in fact, have a much lower response rate to tricyclic antidepressant treatment alone (20-25%) than nondelusional depressives (70-80%). The combination treatment with tricyclic and neuroleptic drugs leads to a dramatic improvement in the response rate in these patients (68-95%). The drugs most widely used are, for tricyclics, amitryptiline (150-215 mg/day) and desipramine (150-200 mg/day), and for neuroleptics, perphenazine (30-50 mg/day), but good results have also been reported with haloperidol (8-20 mg/day). The better results obtained with the tricyclic-neuroleptic association seem to be related to 3 factors: an increased tricyclic plasma level due to a competitive hynibition in the hepatic hydroxilation processes caused by neuroleptic agents: a dopaminergic blockade and an increased serotonergic and noradrenergic activity. Treatment with neuroleptics alone improves the symptomatology only in 19-50% of the patients. If the patient does not show a good response to the combination of tricyclics and neuroleptics, lithium augmentation (600-1200 mg/day) notably ameliorates the rates of clinical response (80-90% of cases). The treatment of delusional depressive patients with amoxapine leads to positive results in 70-80% of cases. Very good results have also been noted with bupropione (300-750 mg/day) after only a week of therapy. A complete symptomatological remission has been observed with 1-Dopa (1000 mg/day). The relatively low number of delusional depressive patients treated with SSRI to date does not allow to draw any consistent and definite conclusion on their real efficacy in this severe form of depression. For the continuation treatment it is recommended to continue the tricyclic-neuroleptic treatment for at least 6 months, at the lowest neuroleptic dosage which allows a long lasting clinical remission. Once the clinical remission is complete, the neuroleptic agent can be gradually tapered in some months, unless the patient had previous recurrence with the tricyclic agent alone. To the patients who show a symptomatological re-exacerbation during neuroleptic tapering, must be given again the combination treatment. In these cases it is important to assess more often and carefully the patient because of the increased risk of tardive diskinesia. Inconsistent results have been reported regarding the role of lithium in preventing relapses and recurrences: some authors suggest a prophylactic treatment with lithium and/o tricyclics in monotherapy to avoid the risks linked to a long-lasting neuroleptic treatment; others authors have documented a higher risk of relapse with lithium and/o tricyclics in monotherapy than with the tricyclic-neuroleptic combination treatment.