Metals accumulation affects bone and muscle in osteoporotic patients: A pilot study.

Osteoporosis is the most common bone disease, characterized by decreased bone mineral density (BMD) and often associated to decreased muscle mass and function. Metal exposure plays a role in the pathophysiology of osteoporosis and affects also muscle quality. The aim of this study was to assess the association between metal levels in bone and muscle samples and the degeneration of these tissues. A total of 58 subjects (30 male and 28 female) was enrolled and classified in osteoporotic (OP, n = 8), osteopenic (Ope, n = 30) and healthy (CTR, n = 20) subjects, according to BMD measures. Femoral head bone samples and vastus lateralis muscle samples were collected during hip arthroplasty surgeries. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed increased levels of Al, Cd and Pb in OP and Ope bone tissue compared to CTR subjects (p = 0.04, p = 0.005 and p = 0.01, respectively). Whereas, increased levels of Co, Cd and Pb were measured in OP and Ope muscle tissues, compared to CTRs (p < 0.001, p = 0.02 and p = 0.01, respectively). In addition, Al, Cd and Pb levels in bone and Cd and Co levels in muscle were negatively correlated with BMD. A negative association among Co, Cd, Cr and Hg levels and muscle fibers diameter was also observed in muscle tissues. This study assessed that metal exposure can affects bone and muscle tissue quality and may contribute to the onset and progression of musculoskeletal diseases such as osteoporosis. Therefore, it is important to implement metal exposure assessment and their impact on disease development, in order to manage and prevent metal accumulation effects on bone and muscle quality.

Improvement in dietary diversity and feeding habits of malnourished under-five children attending supplementary feeding programmmes: a community-based cross-sectional study in Zambia.

A community-based cross-sectional study was conducted on 390 under-five malnourished children enrolled in the Rainbow Project supplementary feeding programmmes-SFPs. Dietary diversity, feeding habits and nutritional status at admission (T1) and at discharge (T2) were compared. At T1 the diet was monotonous and unbalanced, with a progressive decline in dietary diversity and anthropometric values noted with children's age growth (p < 0.001). Significant improvements were registered at T2: DDS 5.1 ± 1.1 SD vs. 8.3 ± 1.0 SD; meal frequency 3.0 ± 0.6 SD vs. 4.9 ± 0.2 SD; animal-protein consumed 62.8% vs. 90.5%; drinking water treated 41.0% vs. 97.2%. At T1, the risk of having ZMUAC < 2.5SD increased when teenage motherhood (AOR: 5.3; CI: 1.8-15.2; p = 0.002), followed by children's age >2 years (AOR: 1.9; CI: 1.1-3.5; p = 0.020). Children's age was associated with an increased risk of WAZ < 2.5 SD (AOR: 4.9; CI: 2.4-10.4; p < 0.001). When considering inadequate DDS, the variable associated was breastfeeding cessation (AOR: 12.0; CI: 4.6-31.4; p < 0.001). Rainbow's SFPs have proved effective in treating under-five malnourished children, irrespective of the severity of malnutrition.

Reduction of Waiting Times and Patients Leaving Without Being Seen in the Tertiary Pediatric Emergency Department: A Comparative Observational Study.

OBJECTIVES: Analyze the effectiveness of an intervention to reduce waiting time and patients leaving without being seen in the pediatric emergency department. METHODS: A comparative observational study was carried out from November 2018 to April 2019.Patients aged 3 months to 17 years were included. The new organizational model consisted of a dedicated outpatients' clinic for nonurgent codes and a fast track for traumatic and surgical emergency cases. RESULTS: The comparative group included 14,822, and the intervention group included 15,585 patients. The new organizational model significantly reduced the numbers of patients who left the ED without being seen from 12.9% to 5.9%. CONCLUSIONS: This new organizational model in the pediatric emergency department could be successfully used to reduce overcrowding, waiting time, and the numbers of patients leaving without being seen. However, more needs to be done by the pediatric services in the community to reduce nonurgent accesses to the emergency department.

Systematic review and meta-analysis of recent high-quality studies on exposure to particulate matter and risk of lung cancer.

BACKGROUND: Several aspects of the association between exposure to air pollution and risk of lung cancer remain unclear. OBJECTIVE: We aimed at performing a meta-analysis of high-quality cohort studies on exposure to particulate matter (PM) 10 and PM2.5 and risk of lung cancer. METHODS: We identified cohort studies published since 2004, that reported risk estimates of lung cancer for exposure to PM2.5 and PM10 adjusted for tobacco smoking and socioeconomic status, and conducted a meta-analysis based on random-effects models, including stratification by outcome, sex, country, tobacco smoking, and age. RESULTS: Results on PM2.5 exposure were available from 15 studies; the summary relative risk (RR) for an increase of 10 µg/m3 was 1.16 (95% confidence interval [CI] 1.09, 1.23). The corresponding RR for PM10 exposure was 1.23 (95 CI 1.05, 1.40; seven studies). A higher risk was suggested in studies based on lung cancer mortality and in studies conducted in East Asia, while no difference was shown according to sex, smoking status or age. There was no suggestion of publication bias. CONCLUSIONS: Our meta-analysis supported the hypothesis of an association between exposure to PM2.5 or PM10 and risk of lung cancer, and provided evidence that the magnitude of the risk might be higher than previously estimated, and might be modified by outcome and geographic region.

'Too many BeEPs in our teens!' Behavioral and emotional problems in a large group of Italian adolescents.

BACKGROUND: One in six adolescents suffers from mental health problems. Despite the presence of general information on Italian adolescents' mental health, researches conducted with standardized assessment tools are scarce in the literature. We evaluated the prevalence of self-reported behavioral and emotional problems in a group of Italian adolescents and examined their relation to socio-demographical variables. METHODS: This population-based sampling survey was conducted on high school students aged 14-18 from urban areas of Rome and Latina. Participants completed Youth Self-Report (YSR) and a socio-demographic schedule to collect information on age, gender, type of school attended, socio-economic status, urbanicity. RESULTS: Final sample consisted of 1400 adolescents (38.61% male, mean age 16 years, s.d. 1.42). Prevalence of Internalizing Problems, Externalizing Problems and Total Problems was 29.55%, 18.34% and 24.13%. In our multivariable model, Internalizing Symptoms were not explained by sociodemographic variables while Externalizing Symptoms were explained by Male Gender [OR = 1.53 (1.14-2.06)], older age [OR = 2.06 (1.52-2.79)] and attending a Technical and Professional Institute [OR = 2.15 (1.53-3.02)], with an adjusted R2 = 4.32%. Total Problems were explained by School Type [Technical and Professional Institutes and Art and Humanities v. Grammar and Science School; OR respectively 1.93 (1.40-2.67) and 1.64 (1.08-2.47)], adjusted R2 = 1.94. CONCLUSIONS: The study provides, for the first time, evidence of a great prevalence of self-reported behavioral and emotional problems in a large sample of Italian adolescents, highlighting the role of different socio-demographic variables as risk factors for externalizing behaviors. Our results emphasize the urgent need for implementing prevention programs on mental health in adolescence.

Social determinants of male partner attendance in women's prevention-of mother-to-child transmission program in Malawi.

BACKGROUND: Male partners are rarely present during PMTCT (Prevention-Mother-To-Child-Transmission) services in Sub-Saharan Africa (SSA). Male involvement is increasingly recognised as an important element of women's access to care. This study aims to identify the socio-demographic characteristics, HIV-Knowledge, Attitude and Practice (KAP) among women accompanied and not accompanied by their male partners. METHODS: We included pregnant women enrolled in PMTCT programme between August 2018 and November 2019 in the Southern Region of Malawi. Eligible women were aged 18 years or older, living with a male partner, enrolled for the first time in one of the four selected facilities. We provided a KAP survey to women and their partners attending the facilities. Our primary objective was to assess and analyse the proportion of women who were accompanied by their partner at least once. We applied descriptive statistics and logistic regressions to study the association between being accompanied and explanatory variables. RESULTS: We enrolled 128 HIV-positive women: 82 (64.1%) were accompanied by their male partners and 46 (35.9%) were alone. In the multivariable model, women's unemployment and owning a means of transport are negatively associated with male attendance (respectively adjusted OR 0.32 [95% CI, 0.11-0.82] and 0.23 [95% CI, 0.07-0.77]), whereas, in the univariable model, high women's level of knowledge of HIV is positively associated with male attendance (OR 2.17 [95% CI, 1.03-4.58]). Level of attitude and practice toward HIV were not significantly associated to our study variable. CONCLUSIONS: Our study shows a high male attendance in Malawi compared to other studies performed in SSA. This study highlights that women's level of knowledge on HIV and their economic condition (employment and owning a means of transport) affects male attendance. Moreover, the study points out that gender power relationships and stringent gender norms play a crucial role thus they should be considered to enhance male involvement.

Access to health care, nutrition and dietary habits among school-age children living in socio-economic inequality contexts: results from the "ForGood: Sport is Well-Being" programme.

Social frailty is a warring phenomenon in Europe, negatively impacting children's health and nutrition. We present the results of a social programme facilitating access to physical activities for vulnerable children in Italy. 311 school-age children enrolled in the programme between 2015 and 2017 were assessed for health and lifestyle, anthropometric and nutritional status. Data were compared by origin (Italians vs. immigrants) and then immigrants were split into sub-groups: first- and second-generation. Poor socio-economic status exposed children to a lack of access to health services, and drove imbalanced eating behaviour. 20.8% of children were not registered with the National Health Services (immigrants p < .0001); 22% were not fully vaccinated (no differences between groups). A double burden of malnutrition coexisted: overweight was higher for Italians, underweight and poor linear growth for immigrants. Nearly 40% of children had a poor Mediterranean Diet adequacy (KIDMED index). Our findings show that when social programmes, besides their main scope of inclusion and integration, holistically approach their beneficiaries, they can play an important role in monitoring lifestyle conditions and facilitating access to primary health care.

Early assessment of weight velocity can support frontline health workers in predicting malnutrition in HIV-exposed infants: preliminary results from a DREAM cohort in Malawi.

BACKGROUND: Children born to HIV-positive mothers are particularly susceptible to malnutrition. Currently, monitoring programs rely on punctual anthropometric measurements to assess child growth. Growth velocities could be an additional tool in identifying critical time windows for prevention and implementation of early intervention for malnutrition. METHODS: A retrospective analysis was conducted using data from 817 HIV exposed but uninfected children extracted from DREAM program database. By using the WHO reference for growth standards, patterns of weight velocity for different intervals of assessment from one to 18 months of age were explored. Odds ratios and multinomial logistic regressions between selected weight velocity Z-scores thresholds and successive malnutrition indices (at 6, 12, 18 months of age) were calculated. RESULTS: Weight velocity was above the standard mean in the first 3 months, then progressively declined over time. In children with normal nutritional status, significant risks of becoming malnourished (mild malnutrition - underweight [OR 10.8; 95% CI: 4.5-26], chronic malnutrition - stunting [OR 8.3; 95% CI: 2-34.9] and acute malnutrition - wasting [OR 11.7; 95% CI: 1.5-90.5]) started when weight velocity Z-scores <0, at all interval ages. Multinomial regression showed that in the first 6 months, the weight velocity decrements strongly impacted on underweight (OR 17.9; 95% CI: 4-80.7), while the risk of Stunting occurred later at 18 months (OR 8.7; 95% CI: 4.3-17.6), with highest impact at the lowest thresholds. CONCLUSIONS: The assessment of weight velocity Z-scores, coupled with the already validated malnutrition indices, can support frontline health workers in early prediction of child malnutrition and performing nutritional counselling in the context of HIV/AIDS and food insecurity.

The effectiveness of interventions to involve men living with HIV positive pregnant women in low-income countries: a systematic review of the literature.

BACKGROUND: Male involvement (MI) along the continuum of HIV healthcare services has been promoted as a critical intervention in low-income countries and represents one of the reasons for dropout and low retention of women along the cascade of care. The present review aims to identify interventions adopted to improve MI across Antenatal Clinics (ANCs). METHODS: For this systematic review, we searched electronic databases, including Scopus, PubMed, Web of Science (from 2008 to 2018) in English language. We included all interventions explicitly aimed at involving partners in pregnant women's HIV continuum of care and we excluded studies performed in developed countries, not involving pregnant women. We followed the PRISMA checklist. RESULTS: We identified a total of 1694 records and excluded 1651 after duplicates were removed and abstract eligibility assessments were performed. Forty-three full-text articles were screened, but only 12 studies were included. Recurrent intermediate outcomes were antenatal partner attendance rate and male HIV testing. We subdivided articles according to the type of intervention: single intervention (7) and multiple interventions (5). Among single interventions, two studies evaluated the use of an invitation letter sent via women to encourage male attendance to the ANC. Four Randomized Controlled Trials (RCTs) compared the invitation card (standard of care, SC) to word of mouth, information letter, home visit and invitation card plus partner tracing. The partner attendance rate was lower in SC than in the intervention arm in three RCTs: information letter (14.2% vs 16.2%), home-visit (39% vs 87%) and invitation card plus partner tracing (52% vs 74%). Home visit strategies seemed the most effective. One study evaluated words of encouragement adopted to trigger women to invite their partners. Among multiple interventions, the most effective strategies in terms of male attendance included health promotion through education and healthcare worker development. These interventions were more likely to be effective in promoting MI than single interventions. CONCLUSIONS: From the review emerges the importance of male involvement in HIV cascade for pregnant women in countries with a significant HIV incidence and the need to define more precise indicators for measuring MI.

Immune Activation and Microbial Translocation Markers in HIV-Exposed Uninfected Malawian Infants in the First Year of Life.

BACKGROUND: HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life. METHODS: Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally. RESULTS: Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 µg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018). CONCLUSION: We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings.

A multivariate genetic analysis confirms rs5010528 in the human leucocyte antigen-C locus as a significant contributor to Stevens-Johnson syndrome/toxic epidermal necrolysis susceptibility in a Mozambique HIV population treated with nevirapine.

Objectives: Nevirapine is used in developing countries for the treatment of HIV infection, but its use is associated with rare serious adverse reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Recently, an association between rs5010528 in the human leucocyte antigen (HLA)-C locus and SJS/TEN susceptibility has been described in sub-Saharan populations. Our aim was to verify this association in a population of nevirapine-treated patients from Mozambique. Methods: The rs5010528 SNP was analysed by direct sequencing in 27 patients who had developed SJS/TEN and 75 patients who did not develop adverse reactions after nevirapine treatment. A case-control association study was conducted. A multivariate analysis was performed in order to evaluate the role of HLA-C also in relation to other susceptibility genetic factors (CYP2B6, TRAF3IP2, HCP5, PSORS1C1 and GSTM1 genes). Results: rs5010528 was significantly associated with a higher risk of developing SJS/TEN; the variant allele was more frequent in cases than in controls, conferring a high risk of developing this adverse reaction in carriers (OR = 5.72 and P = 0.0002 at genotype level, OR = 3.51 and P = 0.0002 at allelic level). The multivariate analysis showed that the HLA-C SNP, CYP2B6 (rs28399499), TRAF3IP2 (rs76228616) and GSTM1 (null genotype) can explain 25% of the susceptibility to this reaction, with the HLA-C SNP as the most significant contributor (P = 0.02 and OR = 5.64). Conclusions: Our study confirmed the association of the rs5010528 SNP in the HLA-C region with susceptibility to developing SJS/TEN in a population from Mozambique, suggesting that it could be a good genomic biomarker for SJS/TEN susceptibility in different sub-Saharan populations.

Antibody response to hepatitis B vaccine in HIV-exposed infants in Malawi and correlation with HBV infection acquisition.

The aim of this study was to assess the immune response to HBV vaccine in HIV-exposed infants and to correlate it to HBV infection acquisition. Protective anti-HBs levels (>10 mIU/mL) were found in 54/58 (93.2%) infants at 6 months, 126/144 (87.5%) at 12 months and 141/176 (80.1%) children at 24 months. HBV infection (seven children were HBsAg + at Month 24) occurred also in the presence of levels above 10 mIU/mL. Our findings indicate limited impact of HIV exposure on anti-HBV immune response, but suggest that levels >10 mIU/mL may be required to confer protection in this context.

Deficit of IgG2 in HIV-positive pregnant women is responsible of inadequate IgG2 levels in their HIV-uninfected children in Malawi.

BACKGROUND: Transplacental passage of IgGs is impaired in HIV + pregnant women, possibly determining an inadequate immunological protection in their children. We aimed to determine the impact of maternal immunological IgG profile and immunoactivation status on the efficiency of transplacental passage of IgG subclasses in HIV + mothers. METHODS: 16 mother/infants pairs were studied in Malawi. Mothers received antiretroviral therapy (ART) from the third trimester of pregnancy. Determinations of pre-ART levels of maternal sCD14, of IgG subclasses in mothers at delivery and in their 1-month-old infants, were performed using commercial ELISA kits. RESULTS: At delivery, after a median of 10 weeks of ART, 12/16 mothers were hypergammaglobulinemic, with IgG levels (20.5 mg/ml, 95% CI:18.8-26.8) directly correlated to the plasmatic levels of sCD14 (r = 0.640, p = 0.014). IgG1 levels (17.9 mg/ml) accounted for 82% of IgG, IgG3 and IgG4 levels were in the normal range. A profound deficit of IgG2 was observed both in mothers (0.60 mg/ml) and in infants (0.14 mg/ml). Placental transfer ratio (range 0.16-0.42) did not show a selective impairment between the different IgG subclasses. The transplacental passage of all IgG subclasses was decreased in the presence of maternal IgG over 16 mg/ml (significantly for IgG1, p = 0.031) and of high levels of sCD14 (p = 0.063). CONCLUSIONS: Transplacental passage was reduced for all IgG subclasses and inversely correlated to high levels of maternal IgGs and to the degree of immunoactivation. The profound depression of IgG2 in mothers suggests that IgG2 neonatal levels mostly reflect the maternal deficit rather than a selective impairment of IgG2 transfer.

Frailty as a predictor of mortality and hospital services use in older adults: a cluster analysis in a cohort study.

Background: Lowering mortality and hospitalization of older adults is one of the main goals of public health to improve both health systems' sustainability and older adults' quality of life. The aim of this study is to identify the determinants associated with mortality and the use of hospital services in the population older than 64 years of age. Methods: A randomized sample from the population of the Lazio region (Italy) above the age of 64 was enrolled in 2014 by the administration of a questionnaire to assess frailty; the rates of use of hospital services and mortality in the year following the enrolment have been retrieved by the regional database. Univariable and multivariable analyses addressed the association of health status, social and economic variables with health outcomes. Results: One thousand two hundred and eighty persons were recruited; 52 deaths were reported at 1 year of follow-up (robust 1.8%, frail 10.1% and very frail 19.1%, P < 0.001). The mean rate of use of hospital services was 692.2 per 1000 observation/year (robust 589.5, frail 1191.1 and very frail 848.4, P < 0.001). In the multivariate analysis, the higher rate of use of hospital services was independently associated with functional status, social support, psychological/psychiatric discomfort, availability of home care services and physical health. Conclusions: Frailty, as a multidimensional issue, is also a strong predictor of survival in the short term. The use of the hospital services by older adults is associated mainly with functional status, social resources, psycho-physical status and health service organization factors.

[The progressive patient care program as a model of field training of public health practitioners: the experience of the Roman Public Health Academy]. / L'ospedale ad Intensità di cura come modello di formazione condivisa sul campo: l'esperienza dell'Accademia Romana di Sanità Pubblica.

The management of healthcare facilities has become increasingly complex in recent years, leading to a greater demand for public health physicians in Italy. Public Health physicians are responsible for evaluating community needs, with particular attention to health determinants and, at the same time, to final user feedback. During their training, they must acquire the competencies to manage a wide range of problems. The Roman Public Health Academy (ARSP) was developed to motivate young residents in Public Health to acquire the knowhow, skills and abilities required of a public health practitioner. It therefore implemented a special training program offering different educational opportunities for residents. In particular, the program offers a team of three young residents field training opportunities, allowing them to become engaged in solving complex technical and management problems. In this paper we describe the methods through which, following a specific request by the director of a hospital in Rome, the team supported a project involving the reorganization of several hospital wards. The aim of the reorganization was to enhance the performance and efficiency of the wards, according to the Progressive Patients Care program.

Tuberculosis Case Finding With Combined Rapid Point-of-Care Assays (Xpert MTB/RIF and Determine TB LAM) in HIV-Positive Individuals Starting Antiretroviral Therapy in Mozambique.

BACKGROUND: Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. METHODS: At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. RESULTS: Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/µL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. CONCLUSIONS: The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation in very advanced HIV/tuberculosis disease.

CMV infection in a cohort of HIV-exposed infants born to mothers receiving antiretroviral therapy during pregnancy and breastfeeding.

Antiretroviral therapy has been shown to reduce rates of congenital CMV infection. Little information is available on the possible impact of antiretroviral therapy on postnatal breastfeeding-associated CMV infection acquisition. A cohort of 89 HIV-infected mothers and their children was studied. Women received antiretroviral therapy from week 25 of gestation until 6 months postpartum or indefinitely if meeting the criteria for treatment. All women were evaluated for CMV IgG presence and CMV DNA in breast milk. Children were tested for CMV infection by either the presence of IgM or the presence of CMV DNA in plasma at 1, 6 and 12 months and by the presence of IgG at 24 months. All mothers had high titers of CMV DNA in breast milk (5.7 log at Month 1 and 5.1 log at Month 6). Cumulative CMV infection rates were 60.3 % at Month 6, 69 % at Month 12 and 96.4 % at Month 24. There was a significant negative correlation between the duration of antiretroviral treatment during pregnancy and levels of CMV DNA in breast milk at Month 1 (P = 0.033). There was a trend for a correlation between high titers of CMV DNA in breast milk at 6 months and CMV infection at 6 months (P = 0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection acquisition.

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: implications for the activity of next-line regimens from a longitudinal study in Mozambique.

BACKGROUND: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC). METHODS AND RESULTS: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/µl. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL. CONCLUSIONS: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.

Impact of glutathione transferases genes polymorphisms in nevirapine adverse reactions: a possible role for GSTM1 in SJS/TEN susceptibility.

PURPOSE: Nevirapine (NVP) is used in developing countries as first-line treatment of HIV infection. Unfortunately, its use is associated with common serious adverse drug reactions, such as liver toxicity and the most severe and rare Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). GSTT1 and GSTM1 genes code for enzymes involved in the metabolism of a wide range of drugs. We hypothesized that this gene variability could be implicated in NVP adverse reactions. METHODS: We analyzed the GSTM1 and GSTT1 null genotypes by multiplex PCR in a population of 181 patients from Mozambique, treated with NVP. A case/control association study was performed. We also counted the number of risk alleles in SJS/TEN patients and in controls, including the GSTM1 null genotype and four previously identified risk alleles in CYP2B6, HCP5, and TRAF3IP2 genes. RESULTS: Among patients, 27 had developed SJS/TEN and 76 had developed hepatotoxicity during the treatment. The GSTM1 null genotype was more frequent in the cases with SJS/TEN than in the controls (OR = 2.94, P = 0.027). This association is also observed when other risk factors are taken into account, by a multivariate analysis (P = 0.024 and OR = 3.58). The risk allele counting analysis revealed a significantly higher risk for SJS/TEN in patients carrying three or four risk alleles. Moreover, all subjects with five or six risk alleles developed SJS/TEN, while subjects without any risk alleles were present only in the control group. CONCLUSIONS: We observed an association between GSTM1 and SJS/TEN susceptibility. Moreover, GSTM1 contributes to the definition of a genetic risk profile for SJS/TEN susceptibility.

The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group.

BACKGROUND: There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects. However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration. This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed. Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM. CONCLUSIONS: In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.