Influences on Adherence to Antiretroviral Therapy (ART) in Early-Stage HIV Disease: Qualitative Study from Uganda and South Africa.

Realization of optimal treatment and prevention benefits in the era of universal antiretroviral therapy (ART) and "U=U" (undetectable = untransmittable) requires high adherence at all stages of HIV disease. This article draws upon qualitative interview data to characterize two types of influences on ART adherence for 100 Ugandans and South Africans initiating ART during early-stage HIV infection. Positive influences are: (a) behavioral strategies supporting adherence; (b) preserving health through adherence; (c) support from others; and (d) motivating effect of adherence monitoring. "De-stabilizing experiences" (mobility, loss, pregnancy) as barriers are posited to impact adherence indirectly through intervening consequences (e.g. exacerbation of poverty). Positive influences overlap substantially with adherence facilitators described for later-stage adherers in previous research. Adherence support strategies and interventions effective for persons initiating ART later in HIV disease are likely also to be helpful to individuals beginning treatment immediately upon confirmation of infection. De-stabilizing experiences merit additional investigation across varying populations.

Predictors of 30-day and 90-day mortality among hemorrhagic and ischemic stroke patients in urban Uganda: a prospective hospital-based cohort study.

BACKGROUND: We report here on a prospective hospital-based cohort study that investigates predictors of 30-day and 90-day mortality and functional disability among Ugandan stroke patients. METHODS: Between December 2016 and March 2019, we enrolled consecutive hemorrhagic stroke and ischemic stroke patients at St Francis Hospital Nsambya, Kampala, Uganda. The primary outcome measure was mortality at 30 and 90 days. The modified Ranking Scale wasused to assess the level of disability and mortality after stroke. Stroke severity at admission was assessed using the National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS). Examination included clinical neurological evaluation, laboratory tests and brain computed tomography (CT) scan. Kaplan-Meier curves and multivariate Cox proportional hazard model were used for unadjusted and adjusted analysis to predict mortality. RESULTS: We enrolled 141 patients; 48 (34%) were male, mean age was 63.2 (+ 15.4) years old; 90 (64%) had ischemic and 51 (36%) had hemorrhagic stroke; 81 (57%) were elderly (≥ 60 years) patients. Overall mortality was 44 (31%); 31 (23%) patients died within the first 30 days post-stroke and, an additional 13 (14%) died within 90 days post-stroke. Mortality for hemorrhagic stroke was 19 (37.3%) and 25 (27.8%) for ischemic stroke. After adjusting for age and sex, a GCS score below < 9 (adjusted hazard ratio [aHR] =3.49, 95% CI: 1.39-8.75) was a significant predictor of 30-day mortality. GCS score < 9 (aHR =4.34 (95% CI: 1.85-10.2), stroke severity (NIHSS ≥21) (aHR = 2.63, 95% CI: (1.68-10.5) and haemorrhagic stroke type (aHR = 2.30, 95% CI: 1.13-4.66) were significant predictors of 90-day mortality. Shorter hospital stay of 7-13 days (aHR = 0.31, 95% CI: 0.11-0.93) and being married (aHR = 0.22 (95% CI: 0.06-0.84) had protective effects for 30 and 90-day mortality respectively. CONCLUSION: Mortality is high in the acute and sub-acute phase of stroke. Low levels of consciousness at admission, stroke severity, and hemorrhagic stroke were associated with increased higher mortality in this cohort of Ugandan stroke patients. Being married provided a protective effect for 90-day mortality. Given the high mortality during the acute phase, critically ill stroke patients would benefit from early interventions established as the post-stroke- standard of care in the country.

HIV Infection and risk of postpartum infection, complications and mortality in rural Uganda.

HIV infection may increase risk of postpartum infection and infection-related mortality. We hypothesized that postpartum infection incidence and attributable mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected women. We performed a prospective cohort study of 4231 women presenting to a regional referral hospital in 2015 for delivery or postpartum care. All febrile or hypothermic women, and a subset of randomly selected normothermic women were followed during hospitalization and with 6-week postpartum phone interviews. The primary outcome was in-hospital postpartum infection. Secondary outcomes included in-hospital complications (mortality, re-operation, intensive care unit transfer, need for imaging or blood transfusion) and 6-week mortality. We performed multivariable regression analyses to estimate adjusted differences in each outcome by HIV serostatus. Mean age was 25.2 years and 481 participants (11%) were HIV-infected. Median CD4+ count was 487 (IQR 325, 696) cells/mm3, and 90% of HIV-infected women (193/215 selected for in-depth survey) were on antiretroviral therapy. Overall, 5% (205/4231) of women developed fever or hypothermia. Cumulative in-hospital postpartum infection incidence was 2.0% and did not differ by HIV status (aOR 1.4, 95% CI 0.6-3.3, P = 0.49). However, more HIV-infected women developed postpartum complications (4.4% vs. 1.2%, P = 0.001). In-hospital mortality was rare (2/1768, 0.1%), and remained so at 6 weeks (4/1526, 0.3%), without differences by HIV serostatus (P = 1.0 and 0.31, respectively). For women in rural Uganda with high rates of antiretroviral therapy coverage, HIV infection did not predict postpartum infection or mortality, but was associated with increased risk of postpartum complications.

Evaluation of masseter muscle in different vertical skeletal patterns in growing patients.

AIM: The present study aimed to evaluate the relationship between masseter size, maxillary intermolar width and craniofacial vertical skeletal pattern. STUDY DESIGN: The study followed a prospective longitudinal design and enrolled 61 subjects (30 males and 31 females), 9-14 years of age (mean age 11.5) at 2-3 CVM stage. The participants were divided into three groups based on their vertical skeletal pattern which was estimated using the Frankfurt-mandibular plane angle: low-angle group (L-A), normal-angle group (N-A), high-angle group (H-A). An additional gender-based distinction was made. Maxillary intermolar width was measured on the maxillary cast of each patient by means of an electronic caliper; masseter volume was estimated by using magnetic resonance (MR) and masseter thickness was measured by means of ultrasonography (US). The US registrations were performed during the relaxation state (RS) and the maximum voluntary contraction (MVC) of the muscle. The indipendent samples T- test was used for sex comparisons; the analysis of variance test (ANOVA) was used to evaluate the differences between the three groups in males and females, and the Pearson r correlation coefficient was employed to assess the correlation between maxillary intermolar width and masseter volume. RESULTS AND CONCLUSION: Maxillary intermolar width, masseter volume and thickness showed significant gender differences; all the tested variables decreased significantly according to the facial vertical pattern, with greater values in females, especially in low- and normal-angle subjects; maxillary intermolar width and masseter volume showed significant correlations, higher in females.

Analgesic efficacy of Pericapsular Nerve Group (PENG) block compared with Fascia Iliaca Block (FIB) in the elderly patient with fracture of the proximal femur in the emergency room. A randomised controlled trial.

INTRODUCTION AND OBJECTIVES: Data on the efficacy of PENG (Pericapsular Nerve Group) block in hip trauma pain are scarce. We hypothesized that PENG block was more effective than infra-inguinal ultrasound-guided FIB (Fascia Iliaca block) for pain control in patients aged 65 years or older presenting in the emergency room (ER) with traumatic proximal femoral fracture. MATERIALS AND METHODS: We conducted an exploratory, double-blind, randomized controlled trial. One anaesthesiologist performed the block and another assessed outcomes. Patients were randomly allocated to the PENG group (20 ml ropivacaine 0.375%) or the infrainguinal FIB group (40 ml ropivacaine 0.2%). Standard hypothesis tests (t test or χ2 test) were performed to analyse baseline characteristics and outcome parameters. The primary end-point of the study was analgesic success, defined as "NRS pain score ≤ 4" 30 min after blockade, with PENG vs to FIB. Secondary outcomes were pain at rest ("pain at rest NRS score ≤ 4" 30 min after blockade), duration of analgesia (time to first request for analgesia), need for rescue medication in case of block failure, and complications during blockade. RESULTS: After obtaining ethical committee approval and written informed consent, 60 patients were included. The primary endpoint was achieved in 16 out of 30 patients (53.3%) in the PENG group and in 15 out of 28 patients (53.6%) in the FIB group. Comparison between groups did not show superiority of the PENG vs FIB (P-value .98). CONCLUSIONS: PENG block does not provide better pain than FIB in proximal femoral fracture in elderly patients treated in the ER.

Mycobacterium smegmatis expressing a chimeric protein MPT64-proteolipid protein (PLP) 139-151 reorganizes the PLP-specific T cell repertoire favoring a CD8-mediated response and induces a relapsing experimental autoimmune encephalomyelitis.

We infected SJL mice with a recombinant Mycobacterium smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein 139-151 (p139) fused to MPT64, a secreted protein of Mycobacterium tuberculosis (rMS(p139)). Infected mice developed a relapsing experimental autoimmune encephalomyelitis (EAE), showing a prevailing demyelination of the CNS, and disease severity was significantly lower in comparison with the one that follows immunization with p139. rMS(p139) was not detected in lymph node or spleen in the course of clinical disease development or in the CNS during relapse. Infection with rMS(p139) modified the p139-specific T cell repertoire, recruiting the spontaneous p139-specific repertoire and activating CD4(+) T cells carrying the BV4 semiprivate rearrangement. T cells carrying the public BV10 rearrangement that are consistently found in the CNS during flares of disease were not activated by infection with rMS(p139) because lymph node APCs infected with rMS(p139) selectively fail to present the epitope for which BV10 cells are specific. Simultaneously, rMS(p139) expanded p139-specific CD8(+) cells more efficiently than immunization with peptide in adjuvant. SJL mice vaccinated against the CDR3 sequence of the BV10 public rearrangement reduced usage of the BV10 cells and displayed reduced symptoms during bouts of EAE. Thus, transient peripheral infection with a CNS-cross-reactive nonpathogenic Mycobacterium induces a relapsing EAE that continues long after clearance of the infectious agent. The composition of the self-reactive repertoire activated determines severity and histology of the resulting disease.

Diagnosis of deep-seated lymphomas by endoscopic ultrasound-guided fine needle aspiration combined with flow cytometry.

OBJECTIVE: Although endoscopic ultrasound combined with fine needle aspiration (EUS-FNA) is rapidly becoming the preferred diagnostic approach for the sampling and diagnosis of gastrointestinal and mediastinal malignancies, there are limited data as to its use in the diagnosis of lymphoproliferative disorders. Therefore, we carried out a retrospective evaluation of the performance of EUS-guided FNA combined with flow cytometry (FC) as a tool to improve overall sensitivity and specificity in the diagnosis of lymphoma. METHODS: Of 1560 patients having EUS-guided FNA during the period of the study, a total of 56 patients were evaluated by cytology with FC after EUS-FNA. There was adequate material to perform FC analysis for all but one case. RESULTS: EUS-FNA-FC gave a diagnosis of lymphoma in 11 cases and of reactive lymphadenopathy in 20. A specific histological type was defined by FC alone in eight cases. The remaining cases were diagnosed later by cytology and cell block sections: 13 carcinomas, nine granulomatous lymphadenopathies and one mediastinal extramedullary haematopoiesis. One case was considered only suspicious for lymphoma on cytology and FC but was not confirmed on molecular analysis and one had insufficient material for FC. CONCLUSIONS: Our results show that a combination of EUS-FNA-FC is a feasible and highly accurate method, which may be used for the diagnosis and subtyping of deep-seated lymphoma, providing a significant improvement to cytomorphology alone both for diagnosis and treatment planning, as long as immunocytochemistry is available for non-lymphoma cases.

Proximal Femoral Fractures in the Elderly, Mortality at 30 days and Fast Track: Does It Always Worth It?

Objectives: Proximal femur fractures (PFF) usually occur in ge-riatric patients and lead to high mortality and disability. This study aims to analyze the mortality rate at 30 days in over-65 -years hospitalized patients with proximal femur fractures, comparing the data collected from three public hospitals in Lazio Region, focusing on early surgery outcomes. Materials and Methods: They were gathered data from the Regional Program for the Evaluation of the Outcomes of Health Interventions (P.Re.Val.E.) dated 2019, managed by the Department of Epidemiology of the Regional Health Service of Lazio (DEP), concerning femur fractures' treatment and outcome in elderly patients. Three hospitals were selected (called A, B, or C), belonging to a specific Local He-alth Authority in Rome, and for each of them were identified some indicators (total number of hospitalizations, origin of the admissions, destination of patients, surgery within 48 hours or two days, 30-day mortality, number of hospitalizations). Results: In Hospital A, the mortality rate at 30 days (305 registe-red patients) was 2.6%, the lowest among the hospitals considered. In Hospital B, the total mortality at 30 days (254 registered patients) was 7.48%, above the regional average of 5.95%. In Hospital C, the mortality rate at 30 days (71 registered patients) was 4.23%, below the regional average. Conclusions: P.Re.Val.E. represents a fundamental tool to evaluate the work of the Local Health Authorities and the structures that are part of it. In particular, about proximal femoral fractures in over-65-years patients, the results of surgical treatment in 48 hours and the morta-lity rate at 30 days represent a reproducible index of quality of the healthcare system. However, other variables need to be considered in future studies, taking into account different features of various hospitals, even if they belong to the same Local Health Authority. v.

Tuning the catalytic acidity in Al2O3 nanofibers with mordenite nanocrystals for dehydration reactions.

Alumina (Al2O3) is one of the most used supports in the chemical industry due to its exceptional thermal stability, surface area, and acidic properties. Mesoscopic structured alumina with adequate acidic properties is important in catalysis to enhance the selectivity and conversion of certain reactions and processes. This study introduces a synthetic method based on electrospinning to produce Al2O3 nanofibers (ANFs) with zeolite mordenite (MOR) nanocrystals (hereafter, hybrid ANFs) to tune the textural and surface acidity properties. The hybrid ANFs with electrospinning form a non-woven network with macropores. ANF-HMOR, i.e., ANFs containing protonated mordenite (HMOR), shows the highest total acidity of ca. 276 µmol g-1 as determined with infrared spectroscopy using pyridine as a molecular probe (IR-Py). IR-Py results reveal that Lewis acid sites are prominently present in the hybrid ANFs. Brønsted acid sites are also observed in the hybrid ANFs and are associated with the HMOR presence. The functionality of hybrid ANFs is evaluated during methanol dehydration to dimethyl ether (DME). The proof of concept reaction reveals that ANF-HMOR is the more active and selective catalyst with 87% conversion and nearly 100% selectivity to DME at 573 K. The results demonstrate that the textural properties and the acid site type and content can be modulated in hybrid ANF structures, synergistically improving the selectivity and conversion during the methanol dehydration reaction. From a broader perspective, our results promote the utilization of hybrid structural materials as a means to tune chemical reactions selectively.

Lipid incorporation inhibits Src-dependent assembly of fibronectin and type I collagen by vascular smooth muscle cells.

A vital role of vascular smooth muscle cells (SMCs) is to stabilize the artery wall by elaborating fibrils of type I collagen. This is especially important in atherosclerotic lesions. However, SMCs in these lesions can be laden with lipids and the impact of this modification on collagen fibril formation is unknown. To address this, we converted human vascular SMCs to a foam cell state by incubating them with either LDL or VLDL. Biochemical markers of a SMC phenotype were preserved. However, microscopic tracking revealed a profound perturbation in the ability of the cells to assemble collagen fibrils, reducing assembly by up to 79%. This dysfunction was mirrored by an inability of smooth muscle foam cells to assemble fibronectin. Lipid-loaded SMCs did not display a generalized defect in the actin cytoskeleton and the formation of vinculin-containing focal adhesion complexes was preserved. However, lipid-loaded SMCs were unable to assemble fibrillar adhesion complexes and clustering of tensin and alpha5beta1 integrin was disordered. Moreover, phosphorylation of tensin, required for fibrillar adhesion complex formation, was suppressed by up to 57%, with a concomitant decrease in activation of Src and FAK and restriction of activated Src to the cell edges. Forced activation of Src-FAK signaling in lipid-engorged SMCs rescued both fibrillar adhesion formation and fibrillogenesis. We conclude that lipid accumulation by SMCs disables the machinery for collagen and fibronectin assembly. This previously unknown relationship between atherogenic lipids and integrin-based signaling could underlie plaque vulnerability.

Comparison of Histogram-based Textural Features between Cancerous and Normal Prostatic Tissue in Multiparametric Magnetic Resonance Images.

In the last decade, multiparametric magnetic resonance imaging (mpMRI) has been expanding its role in prostate cancer detection and characterization. In this work, 19 patients with clinically significant peripheral zone (PZ) tumours were studied. Tumour masks annotated on the whole-mount histology sections were mapped on T2-weighted (T2w) and diffusion-weighted (DW) sequences. Gray-level histograms of tumoral and normal tissue were compared using six first-order texture features. Multivariate analysis of variance (MANOVA) was used to compare group means. Mean intensity signal of ADC showed the highest showed the highest area under the receiver operator characteristics curve (AUC) equal to 0.85. MANOVA analysis revealed that ADC features allows a better separation between normal and cancerous tissue with respect to T2w features (ADC: P = 0.0003, AUC = 0.86; T2w: P = 0.03, AUC = 0.74). MANOVA proved that the combination of T2-weighted and apparent diffusion coefficient (ADC) map features increased the AUC to 0.88. Histogram-based features extracted from invivo mpMRI can help discriminating significant PZ PCa.

[Réforme et performance de l'Inspection de la santé et de la Division de la santé au Sud-Kivu en République Démocratique du Congo].

Reform and Performance of the Provincial Health Inspectorate and the Provincial Division of Health of South Kivu in the Democratic Republic of Congo. BACKGROUND: The intermediate level incorporated both the Provincial Health Inspectorate (IPS) and the Provincial Health Division (DPS) of Health. The new constitution of 2006 gave impetus to decentralisation, which became effective in 2015. The reform introduced at the intermediate level clearly separated the IPS and the DPS. This article assesses the effect of this reform on the performance of IPS and DPS in South Kivu, Democratic Republic of Congo. METHODOLOGY: The study is evaluative before and after and covers the period from 2012 to 2017. It uses mixed methods: three techniques were used to collect data including observation, document review and individual interviews. The analysis of the quantitative data concerned the evolution of the indicators; that of qualitative data was carried out by themes from two theoretical models: the ministerial functional framework and the 'Strengths, Weaknesses, Opportunities and Threats' analysis framework (SWOT analysis). Scores were assigned to each managerial function according to their level of performance for better comparison. RESULTS: After the reform, a decline in the performance score of activities devolved to IPS is noted, mainly due to the low funding of activities. On the other hand, in the DPS, the evolution of the score is favorable, because of the strong support given to the reform at this level by the partners and the government. The alignment of partners to a single contract for funding DPS activities is observed. The weak financing of the health sector by the government remains a weak point, however, and the brain drain a threat to institutional sustainability. The introduction of the single financing contract constitutes an opportunity to improve the performance of the provincial management team. DISCUSSION AND CONCLUSION: The study shows the improvement in the performance of managerial functions of the DPS and the regression to the IPS. The low funding of IPS by the Congolese government could jeopardise the reform.

Src and FAK mediate cell-matrix adhesion-dependent activation of Met during transformation of breast epithelial cells.

Cell-matrix adhesion has been shown to promote activation of the hepatocyte growth factor receptor, Met, in a ligand-independent manner. This process has been linked to transformation and tumorigenesis in a variety of cancer types. In the present report, we describe a key role of integrin signaling via the Src/FAK axis in the activation of Met in breast epithelial and carcinoma cells. Expression of an activated Src mutant in non-neoplastic breast epithelial cells or in carcinoma cells was found to increase phosphorylation of Met at regulatory tyrosines in the auto-activation loop domain, correlating with increased cell spreading and filopodia extensions. Furthermore, phosphorylated Met is complexed with beta1 integrins and is co-localized with vinculin and FAK at focal adhesions in epithelial cells expressing activated Src. Conversely, genetic or pharmacological inhibition of Src abrogates constitutive Met phosphorylation in carcinoma cells or epithelial cells expressing activated Src, and inhibits filopodia formation. Interestingly, Src-dependent phosphorylation of Met requires cell-matrix adhesion, as well as actin stress fiber assembly. Phosphorylation of FAK by Src is also required for Src-induced Met phosphorylation, emphasizing the importance of the Src/FAK signaling pathway. However, stimulation of Met phosphorylation by addition of exogenous HGF in epithelial cells is refractory to inhibition of Src family kinases, indicating that HGF-dependent and Src/integrin-dependent Met activation occur via distinct mechanisms. Together these findings demonstrate a novel mechanism by which the Src/FAK axis links signals from the integrin adhesion complex to promote Met activation in breast epithelial cells.

Clinical value of 12 occlusal features for the prediction of disc displacement with reduction (RDC/TMD Axis I group IIa).

The purpose of this study is to quantify the clinical value of 12 occlusal variables for the prediction of disc displacement with reduction diagnosed according to research diagnostic criteria (RDC)/temporomandibular disorder (TMD). Twelve occlusal features were clinically assessed by the same three operators. The sample consisted of 165 TMD patients (65 males, 100 females; mean age: 32.55 +/-11.685 years) with only disc displacement with reduction (RDC/TMD Axis I group IIa) and a control sample of 145 healthy subjects (65 males, 80 females; mean age:31.24+/-12.436 years) diagnosed with RDC/TMD Axis I group 0. A stepwise multiple logistic regression model was used to identify the significant correlation between occlusal features and disease. The odds ratio for disc displacement was 2.84 for absence of canine guidance, 2.14 for mediotrusive interference and 1.75 for retruded contact position (RCP)/maximum intercuspation (MI) slide >or=2 mm. Other occlusal variables did not reveal to be statistically significant. The percentage of the total log likelihood for disc displacement explained by the significant occlusal factors was acceptable with a Nagelkerke's R(2) = 0.124. The final model including the significant occlusal features revealed an optimal discriminant capacity to predict patients with disc displacement with a sensitivity of 63.6% or with a specificity of 64.8% for healthy subjects and an accuracy of 64.2%. Occlusal features showed a low predictive value for detecting disc displacement. Multifactorial complex pathologies such as TMD should be investigated using a multivariate statistical analysis; moreover,the future of aetiopathogenic research in this matter requires a multifactorial approach.

Antiretroviral Therapy Adherence Interruptions Are Associated With Systemic Inflammation Among Ugandans Who Achieved Viral Suppression.

BACKGROUND: Residual systemic inflammation, which is associated with non-AIDS clinical outcomes, may persist despite viral suppression. We assessed the effect of antiretroviral therapy (ART) adherence interruptions on systemic inflammation among Ugandans living with HIV who were virally suppressed. SETTING: We evaluated adults initiating first-line ART at a regional referral hospital clinic in Mbarara, Uganda. METHODS: Plasma concentrations of interleukin-6 (IL-6), D-dimer, soluble sCD14, sCD163, the kynurenine/tryptophan (K/T) ratio, and CD8 T-cell activation (HLA-DR/CD38 coexpression) were measured at baseline and 6 months after ART initiation among participants who achieved viral suppression (<400 copies/mL) at 6 months. ART adherence was monitored electronically. Time spent in an adherence interruption was computed as the percentage of days when the running average adherence was ≤10%. We fit adjusted linear regressions to evaluate the effect of time spent in an interruption on the log-transformed plasma concentrations of the inflammation biomarkers. RESULTS: Of 282 participants, 70% were women, and the median age was 34 years. At baseline, median CD4 and median log viral load were 135 cells per microliter and 5.1 copies per milliliter, respectively. In the adjusted analysis, a running average adherence of <10% was associated with higher sCD14 (+3%; P < 0.008), sCD163 (+5%; P = 0.002), D-dimer (+10%; P = 0.007), HLA-DR/CD8 (+3%; P < 0.025), IL-6 (+14%; P = 0.008), and K:T ratio (+5%; P = 0.002). These findings were largely robust to adjustment for average adherence, as well as higher thresholds of running average adherence, albeit with decreased statistical significance. CONCLUSIONS: Increased time spent in adherence interruptions is associated with increased levels of inflammation, despite viral suppression above and beyond average adherence.

ART adherence and viral suppression are high among most non-pregnant individuals with early-stage, asymptomatic HIV infection: an observational study from Uganda and South Africa.

INTRODUCTION: The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS-free generation depend on high adherence in individuals initiating ART during early-stage HIV infection; however, adherence may be difficult in the absence of illness and associated support. METHODS: From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non-pregnant women with early-stage HIV infection (CD4 > 350 cells/µL), pregnant women with early-stage HIV infection and men and non-pregnant women with late-stage HIV infection (CD4 < 200 cells/µL). Socio-behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically. RESULTS: Adherence data were available for 869 participants: 322 (37%) early/non-pregnant, 199 (23%) early/pregnant and 348 (40%) late/non-pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non-pregnant versus early/pregnant or late/non-pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non-pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking. DISCUSSION: ART adherence among non-pregnant individuals with early-stage infection is as high or higher than with late-stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late-stage infection in South Africa and highlight the need for differentiated care delivery.

Combined cytomegalovirus prophylaxis in lung transplantation: effects on acute rejection, lymphocytic bronchitis/bronchiolitis, and herpesvirus infections.

Lung transplantation recipients are at high risk for herpesvirus infections. We evaluated the effect of combined cytomegalovirus (CMV) prophylaxis on CMV pneumonia, acute rejection episodes (ARE), lymphocytic bronchitis/bronchiolitis (LB), and obliterans bronchiolitis (OB) diagnosed in 180 transbronchial biopsies (TBB) of lung transplant recipients. At our center, 25 patients (control group; 1999-2002) received acyclovir for 12 months and 21 recipients (study group; 2003-2007) received combined CMV prophylaxis consisting of CMV-IG (Cytotect Biotest) for 12 months and ganciclovir or valganciclovir from postoperative day 21 for 3 weeks. Among the study group (since 2005), CMV shell vial viral culture and Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and HHV-7 DNA were determined on BAL specimens. In the study group, the number of LB was significantly lower than in the control group (2% vs 11%; P= .04). Similar results were obtained for ARE (6% vs 17%; P= .04). No difference was observed in OB (5% vs 5%; P= .53, NS). A reduction trend was found in CMV pneumonia (2% vs 7%; P= .23, NS). Logistic regression analysis showed a relationship between prophylaxis and a reduced prevalence of ARE (odds ratio [OR] 3.25, confidence interval [CI] 1.12-9.40; P= .03). Finally, in the study group, BAL EBV-DNA positivity and EBV-CMV coinfections were low (6% and 0%, respectively) compared with other herpesviruses and with the literature. Our data suggested the efficacy of combined CMV prophylaxis to prevent ARE and LB, 2 risk factors for chronic rejection, and a possible role to reduce the trend toward CMV pneumonia and EBV infections.

[Chronic renal failure after hematopoietic stem cell transplantation]. / La nefropatia cronica post-trapianto di cellule staminali emopoietich.

Hematopoietic stem cell transplantation, autologous or allogeneic, is a well established hematology procedure. There can be a number of renal complications in this setting, which may occur in every phase but all strongly influence prognosis. Among the late complications, there is the well-known possibility of progressive chronic renal failure, appearing together with hypertension and modest alterations of the urinary sediment, and characterized by pathological findings of thrombotic microangiopathy, often without the corresponding clinical aspects. This clinical picture must be distinguished from other forms of clinically more severe thrombotic microangiopathy, such as those occurring in the early post-transplant period, and from other causes of renal disease in the hematopoietic stem cell transplantation setting. Total body irradiation, chemotherapeutic drugs, calcineurin inhibitors and opportunistic infections have all been considered as causal factors. The nosological classification is still poorly defined, as are the real prognosis and the best treatment. Kidney biopsy is a necessary tool to make a correct diagnosis, assess the frequency of the condition, make a prognostic judgment, and set up rational treatment.

Law on advance health care directives: a medical perspective.

The paper's authors aim to elaborate on law 22 dicembre 2017, n. 219 , designed to regulate informed consent practices and advance health care directives", which has sparked a passionate debate centered on the substantial innovation achieved over the past decades in bio-medical science and at the same time, the noteworthy accomplishments made in enforcing human and personal rights. Within the paper, article three is delved into, which covers the creation of the so-called DAT ("Disposizioni anticipate di trattamento", advance health care directives), by which patients, in light of possible future incapacity to choose, can express their convictions and decisions on how to be treated and their consent or dissent to undergo treatments and procedures, including artificial nutrition and hydration. The authors peruse the new law's provisions through a medical perspective, and observe how they are heavily tilted towards patient choice, thus making doctors little more than mere tools of such decisions.

Disruption by interferon-alpha of an autocrine interleukin-6 growth loop in IL-6-dependent U266 myeloma cells by homologous and heterologous down-regulation of the IL-6 receptor alpha- and beta-chains.

IL-6 is an autocrine growth factor for U266 myeloma cells and their growth is inhibited by IFN-alpha or IL-6 mAb. We asked, therefore, whether IFN-alpha-induced growth inhibition involved IL-6. IFN-alpha and mAb against IL-6, the IL-6R alpha-(gp80) or beta-chain (gp130) potently inhibited U266 cells. Remarkably, this effect occurred despite IFN-alpha-augmented secretion of endogenous IL-6. However, examining the IL-6R revealed that IFN-alpha drastically curtailed expression of the IL-6R alpha- and beta-chain. This effect occurred on two different levels (protein and mRNA) and by two different mechanisms (directly and indirectly through IL-6). First, IFN-alpha, but not IL-6, greatly decreased gp80 and, to a lesser extent, gp130 mRNA levels which resulted in a loss of IL-6 binding sites. Second, IFN-alpha-induced IL-6 predominantly down-regulated membrane-bound gp130. IFN-alpha-mediated decrease of gp80 levels was not detected on IL-6-independent myeloma (RPMI 8226) or myeloid cells (U937). We conclude that IFN-alpha inhibited IL-6-dependent myeloma cell growth by depriving U266 cells of an essential component of their autocrine growth loop, a functional IL-6R.