Characteristics of TPT initiation and completion among people living with HIV.

BACKGROUND: TB preventive treatment (TPT) reduces morbidity and mortality among people living with HIV (PLHIV). Despite the successful scale-up of TPT in Malawi, monitoring and evaluation have been suboptimal. We utilized the Malawi Population-Based HIV Impact Assessment (MPHIA) 2020-2021 survey data to estimate TPT uptake and completion among self-reported HIV-positive persons. METHODS: We estimated the proportion of HIV-positive respondents who had ever undergone TPT, and determined the percentage of those currently on TPT who had completed more than 6 months of treatment. Bivariate and multivariable logistic regression were performed to calculate the odds ratios for factors associated with ever-taking TPT. All variables were self-reported, and the analysis was weighted and accounted for in the survey design. RESULTS: Of the HIV+ respondents, 38.8% (95% CI 36.4-41.3) had ever taken TPT. The adjusted odds of ever taking TPT were 8.0 and 5.2 times as high in the Central and Southern regions, respectively, compared to the Northern region; 1.9 times higher among those in the highest wealth quintile, and 2.1 times higher for those on antiretroviral therapy >10 years. Of those currently taking TPT, 56.2% completed >6 months of TPT. CONCLUSION: These results suggest low TPT uptake and >6 months' completion rates among self-reported HIV+ persons. Initiatives to create demand and strengthen adherence would improve TPT uptake.

CONTEXTE: Le traitement préventif de la TB (TPT) réduit la morbidité et la mortalité chez les personnes vivant avec le VIH (PVVIH). Malgré l'extension réussie du TPT au Malawi, le suivi et l'évaluation n'ont pas été optimaux. Nous avons utilisé les données de l'enquête MPHIA (Malawi Population-Based HIV Impact Assessment) 2020­2021 pour estimer l'adoption et l'achèvement du TPT parmi les personnes se déclarant séropositives. MÉTHODES: Nous avons estimé la proportion de répondants séropositifs qui avaient déjà subi un TPT et déterminé le pourcentage de ceux qui sont actuellement sous TPT et qui ont terminé plus de 6 mois de traitement. Une régression logistique bivariée et multivariable a été effectuée pour calculer les rapports de cotes des facteurs associés au fait d'avoir déjà pris un TPT. Toutes les variables étaient autodéclarées et l'analyse a été pondérée et prise en compte dans la conception de l'enquête. RÉSULTATS: Parmi les répondants séropositifs, 38,8% (IC 95% 36,4­41,3) avaient déjà pris du TPT. Les probabilités ajustées de prise de TPT étaient 8,0 et 5,2 fois plus élevées dans les régions du centre et du sud, respectivement, que dans la région du nord ; 1,9 fois plus élevées chez les personnes appartenant au quintile de richesse le plus élevé, et 2,1 fois plus élevées chez les personnes suivant une thérapie antirétrovirale depuis plus de 10 ans. Parmi ceux qui prennent actuellement un TPT, 56,2% ont terminé >6 mois de TPT. CONCLUSION: Ces résultats suggèrent un faible taux d'utilisation du TPT et des taux d'achèvement de >6 mois parmi les personnes déclarées séropositives. Des initiatives visant à créer une demande et à renforcer l'adhésion permettraient d'améliorer l'utilisation du TPT.

In memory of Giovanni Berlinguer. The Man, the Scientist, the Politician.

On this occasion I am very grateful to the Academic Authorities for having asked me to illustrate the life of Giovanni Berlinguer as a Researcher, a Professor and a Doctor of Public Health. I will try to fulfill this duty, perhaps with some reservations, because I find it almost impossible to think of Giovanni as a researcher and a professor separately from his complex personality and his role as a politician and a brilliant and prolific writer. This is because Giovanni was an inextricable combination of all these roles, which cannot be described separately.

Exploring the Feasibility of Engaging Traditional Birth Attendants in a Prevention of Mother to Child HIV Transmission Program in Lilongwe; Malawi

Objective:To investigate the willingness of Traditional Birth Attendants (TBAs) to provide single dose antiretroviral prophylaxis to infants born to mothers with HIV and the feasibility of providing the TBAs with antiretroviral medication. Design 2 focus groups with a total of 17 registered TBAs. Setting Lilongwe; Malawi Methods TBAs were recruited by local health workers and participated in focus groups assessing their attitudes towards participation in a PMTCT program. Results TBAs were willing to participate in this prevention of mother-to-child HIV transmission (PMTCT) program and helped identify barriers to their participation. Conclusions:Given appropriate support and training; TBAs' participation in PMTCT programs could be an additional way to deliver medication to mothers and neonates who might otherwise miss crucial doses of medication

Metformin regulates the incretin receptor axis via a pathway dependent on peroxisome proliferator-activated receptor-α in mice.

AIMS/HYPOTHESIS: Metformin is widely used for the treatment of type 2 diabetes. Although it reduces hepatic glucose production, clinical studies show that metformin may reduce plasma dipeptidyl peptidase-4 activity and increase circulating levels of glucagon-like peptide 1 (GLP-1). We examined whether metformin exerts glucoregulatory actions via modulation of the incretin axis. METHODS: Metformin action was assessed in Glp1r(-/-), Gipr(-/-), Glp1r:Gipr(-/-), Pparα (also known as Ppara)(-/-) and hyperglycaemic obese wild-type mice with or without the GLP-1 receptor (GLP1R) antagonist exendin(9-39). Experimental endpoints included glucose tolerance, plasma insulin levels, gastric emptying and food intake. Incretin receptor expression was assessed in isolated islets from metformin-treated wild-type and Pparα(-/-) mice, and in INS-1 832/3 beta cells with or without peroxisome proliferator-activated receptor (PPAR)-α or AMP-activated protein kinase (AMPK) antagonists. RESULTS: In wild-type mice, metformin acutely increased plasma levels of GLP-1, but not those of gastric inhibitory polypeptide or peptide YY; it also improved oral glucose tolerance and reduced gastric emptying. Metformin significantly improved oral glucose tolerance despite loss of incretin action in Glp1r(-/-), Gipr(-/-) and Glp1r(-/-) :Gipr(-/-) mice, and in wild-type mice fed a high-fat diet and treated with exendin(9-39). Levels of mRNA transcripts for Glp1r, Gipr and Pparα were significantly increased in islets from metformin-treated mice. Metformin directly increased Glp1r expression in INS-1 beta cells via a PPAR-α-dependent, AMPK-independent mechanism. Metformin failed to induce incretin receptor gene expression in islets from Pparα(-/-) mice. CONCLUSIONS/INTERPRETATION: As metformin modulates multiple components of the incretin axis, and enhances expression of the Glp1r and related insulinotropic islet receptors through a mechanism requiring PPAR-α, metformin may be mechanistically well suited for combination with incretin-based therapies.

[Assessment of seawater quality along the Asinara Gulf. Note 1: preliminary results of seawater monitoring using Dicentrarchus labrax and Sparus aurata as bioindicators]. / Valutazione della qualità delle acque di mare del Golfo dell'asinara. Nota 1: Risultati preliminari del monitoraggio mediante l'utilizzo dei bioindicatori dicentrarchus labrax e Sparus aurata.

In recent years, physical-chemical, chemical and microbiological testing systems to water's control was matched by the use of "biomarkers" such as algae, nematodes, Anellidi, Porifera, molluscs and arthropods (crustaceans), although these are phylogenetically distant from humans and they differ in methods of recruitment, toxico-kinetics and metabolism of xenobiotics. That is why today the predatory fishes (tuna, mackerel, sea bream, sea bass and swordfish) are among the most widely used in biomonitoring studies. In particular Sparus aurata and Dicentrarchus labrax (sea bream and sea bass) are appropriate in warning of environmental pollution. Moreover since the two species are precious and particularly present in food, they could represent a potential vehicle for the transport of contaminants to humans. To this end, the aim of this note, part of a complex research project launched in line with the provisions of the ministry for the environment, land and sea, is to evaluate the quality of coastal waters by using of Sparus aurata and Dicentrarchus labrax. The results obtained show that the area concerned, at present, is not affected by serious pollution processes, as the human pressure is highlighted by the presence of phenols in sea water and heavy metals (Cd and Hg) in the bioindicators. The detection of these toxic elements in fish species, could also not be directly attributable to any condition of impairment of the environment. However given the accumulation of these contaminants in the parts are edible, the consumption of fish could be a source of exposure particularly for those most exposed to health risks (children, elderly, sick and pregnant women).

Monitoring on chemical and biological pollutants in sea waters of central-northern Sardinia.

INTRODUCTION: The aims of this study are to assess the quality of the coastal waters of central-northern Sardinia through data from a monitoring network and to outline maps and experimental models of environmental risk correlated to the presence of chemical and microbiological contaminants. The area studied is the coast between Capo Falcone and the mouth of the river Coghinas, in the northwestern part of the island. METHODS: In a first phase, 7 sampling stations of sea water and 1 sampling station of bivalve molluscs (Mytilus galloprovincialis Lam.) were identified. For each transept 3 different collection points at respectively 500, 1000, and 3000 meters from the coast for a total 21 sampling sites were identified. In a second phase, another 7 transepts were identified, 2 of which on the island of Asinara. RESULTS: As regards the microbiological monitoring of the sea water, very low concentrations of Total coliforms, Faecal coliforms and Faecal Streptococci were found and no Salmonella were isolated. Chemical analysis of the waters showed a high constant presence of phenols. In the bivalves we found rather high concentrations of Faecal coliforms without any clear seasonal variation, while no Salmonella was isolated in any of the examined samples. DISCUSSION: The results show that the considered area is not affected by serious pollution processes, thus allowing to express a completely satisfactory judgement on its state of health. However anthropic pressure in the considered territory is testified by the presence in the water of high concentrations of phenols. CONCLUSIONS: The results point out to the necessity of targeted and rational preventive action by means of control and protection measures for environmental ecosytems.

Regulation of insulin signalling, glucose uptake and metabolism in rat skeletal muscle cells upon prolonged exposure to resistin.

AIMS/HYPOTHESIS: Debate exists regarding the role of resistin in the pathophysiology of insulin resistance. The aim of this study was to directly assess the effects of resistin (0-24 h) on basal and insulin-stimulated glucose uptake and metabolism in skeletal muscle cells and to investigate the mechanisms responsible for the effects of resistin. METHODS: We used L6 rat skeletal muscle cells and examined [(3)H]2-deoxyglucose uptake, GLUT4 translocation and GLUT protein content. We assessed glucose metabolism by measuring the incorporation of D-[U-(14)C]glucose into glycogen, (14)CO(2) and lactate production, as well as the phosphorylation level and total protein content of insulin signalling proteins, including insulin receptor beta-subunit (IRbeta), insulin receptor substrate (IRS), Akt and glycogen synthase kinase-3beta (GSK-3beta). RESULTS: Treatment of L6 rat skeletal muscle cells with recombinant resistin (50 nmol/l, 0-24 h) reduced levels of basal and insulin-stimulated 2-deoxyglucose uptake and decreased insulin-stimulated GLUT4myc content at the cell surface, with no alteration in the production of GLUT4 or GLUT1. Resistin also decreased glycogen synthesis and GSK-3beta phosphorylation. Insulin-stimulated oxidation of glucose via the Krebs cycle was reduced by resistin, whereas lactate production was unaltered. Although insulin receptor protein level and phosphorylation were unaltered by resistin, production of IRS-1, but not IRS-2, was downregulated and a decreased tyrosine phosphorylation of IRS-1 was detected. Reduced phosphorylation of Akt on T308 and S473 was observed, while total Akt and Akt1, but not Akt2 or Akt3, production was decreased. CONCLUSIONS/INTERPRETATION: Our data show that resistin regulates the function of IRS-1 and Akt1 and decreases GLUT4 translocation and glucose uptake in response to insulin. Selective decreases in insulin-stimulated glucose metabolism via oxidation and conversion to glycogen were also induced by resistin. These observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes in obesity.

[Epidemiological survey on smoking habit among young students in Sardinia. A cross sectional study]. / Il fumo fra i giovani: indagine trasversale nelle scuole medie superiori della Sardegna.

The study reports the prevalence of cigarette smoking among 11401 high school Sardinian students. The prevalence of smokers (40.2%) significantly differs between gender (41.1% males and 38.4% females). Males have an early initiation of smoking with an evident addictive effect by age. 54.3% are daily smokers and 21.4% smoke 15 or more cigarettes per day. More than 50% smoke to look grown-up and to be accepted by the group. Besides age (OR=1.10; 95%CI: 1.06-1.15), other factors are associated with smoke: low education level of father (OR=1.08; 95%CI: 1.02-1.15), no maternal support (OR = 1.73; 95%CI: 1.17-2.54), to have at least one smoker cohabitant (OR=1.66; 95%CI: 1.54-1.80) and alcohol drinking (OR=3.46; 95%CI: 3.04-3.93). The smokers' knowledge on smoke topics significantly differ from non smokers. Our results suggest the need of community preventive interventions, diversified for specific target populations, to modify the students' behaviours so that they respect their own health and that of their fellow citizens.

Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells.

AIMS/HYPOTHESIS: The aim of this study was to determine whether adiponectin elicits glucose uptake via increased GLUT4 translocation and to investigate the metabolic fate of glucose in skeletal muscle cells treated with globular adiponectin. MATERIALS AND METHODS: Basal and insulin-stimulated 2-deoxy-D: -[(3)H]glucose uptake, cell surface myc-tagged GLUT4 content, production of (14)CO(2) by oxidation of D: -[U-(14)C]glucose and [1-(14)C]oleate, and incorporation of D: -[U-(14)C]glucose into glycogen and lactate were measured in the presence and absence of globular adiponectin. RESULTS: RT-PCR and Western blot analysis revealed that L6 cells and rat skeletal muscle cells express AdipoR1 mRNA and protein. Globular adiponectin increased both GLUT4 translocation and glucose uptake by increasing the transport V(max) of glucose without altering the K(m). Interestingly, the incorporation of D: -[U-(14)C]glucose into glycogen under basal and insulin-stimulated conditions was significantly decreased by globular adiponectin, whereas lactate production was increased. Furthermore, globular adiponectin did not affect glucose oxidation, but enhanced phosphorylation of AMP kinase and acetyl-CoA carboxylase, and fatty acid oxidation. CONCLUSIONS/INTERPRETATION: The present study is the first to show that globular adiponectin increases glucose uptake in skeletal muscle cells via GLUT4 translocation and subsequently reduces the rate of glycogen synthesis and shifts glucose metabolism toward lactate production. These effects are consistent with the increased phosphorylation of AMP kinase and acetyl-CoA carboxylase and oxidation of fatty acids induced by globular adiponectin.

Epidemiology of hydatidosis in the province of Sassari, Italy.

Cystic echinococcosis is endemic in certain parts of the world, including Sardinia, Italy. It was performed a study in the province of Sassari in order to evaluate the incidence of the infection in man and the effects of control programs since 1964 to 2002. Data obtained by surgical records, hospital discharge forms, radiological and pathological files were collected using a case report form. During the years 1964-2002, 2702 new cases were identified (average annual incidence: 17 per 100,000) and 1981 (73.3%) were submitted to surgical treatment. In 57.3% municipalities no cases were observed during the years 1998-2002. Males are more affected (56.2%), mostly farmers-shepherdess (68.6 per 100,000) and pensioners (59.6 per 100,000). Control measures led to a significant decline in the incidence rate of hydatidosis during the period 1964-2002, dropping by 27.6 per 100,000. The mean age of surgical patients increased during the years of surveillance, such as the surgical liver/lung ratio as a consequence of a cohort effect. The durability of control programs is the corner stone for obtaining a significant decrease of this infection.

Detection of isoniazid and rifampin resistance in Mycobacterium tuberculosis strains by single-strand conformation polymorphism analysis and restriction fragment length polymorphism.

Anti-Mycobacterium tuberculosis drug-resistance, mainly multi-drug resistance (MDR-TB), represents an important public health problem in several countries. Aim of our study is to identify the presence of these mutations in M. tuberculosis isoniazid- and rifampin-resistant strains isolated in our Institute; to evaluate linkage between type of mutation and level of resistance; to determine the usefulness of easy molecular techniques for rapid detection of such mutations on body specimens. Isoniazid- and rifampin-resistance was tested on 67 M. tuberculosis strains by Single-Strand Conformation Polymorphism (SSCP) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assays, using HaeIII, PstuI, BsteII, BstuI enzymes. Drug-resistance of control strains was determined by cultural techniques (fluorimetry- BACTEC 9120). Cultural assay showed isoniazid- and rifampin-resistance in 6.12 and 2%, respectively (data confirmed by SSCP assay). Mutation of katG, linked to isoniazid resistance, was detected using BstuI enzyme, and mutation of rpoB, expression of reduced sensitivity to rifampin, using HaeIII. 15 body specimens, M. tuberculosis-positive to conventional assays, were tested by SSCP technique. Epidemiologic reports of numerous cases of tuberculosis due to MDR strains induce to detect quickly both Mycobacteria and drug-resistance, in order to start prompt effective therapy. On this basis, molecular assays are useful for a rapid therapeutic decision.

[The debate in Italy and in Europe about the adoption of pneumococcal vaccine in children]. / Il dibattito in corso in Italia ed in Europa sull'adozione della vaccinazione anti-pneumococcica in età pediatrica.

Since the introduction of the conjugate vaccine PnC-7, for the prevention of invasive pneumococcal infections for at-risk children, a controversy has arisen about the need for a universal vaccination under the age of two years. This article reviews the pathogenesis and the changing epidemiological pattern of pneumococcal diseases, the emergence of drug resistant S. pneumoniae and the costs and benefits of vaccination. Furthermore, the recommendations of various European countries and an up to date of the Italian ones are illustrated. It concludes with the public health perspective on the adoption of this pneumococcal vaccine and future recommendations for vaccination.

[Munchausen syndrome by proxy, an unusual presentation]. / Síndrome de Münchausen por poder, una presentación inusual.

We report a 12 year old girl that first consulted for fever with bilateral knee arthralgias. A neurological workout was started due to a progressive gait disturbance, but all results were incongruent with nerve or nerve root lesions, leading to the diagnosis of a functional paralysis. The patient worsened to the point of prostration. Due to the suspicion that the mother was inducing the symptoms, the patient was admitted to the hospital, where she improved notably. She was discharged walking. The improvement during hospital stay confirmed the diagnosis of a Münchausen by proxy syndrome, mimicking a disabling neurological condition.

Pretreatment antibiotic resistance in Helicobacter pylori infection: results of three randomized controlled studies.

BACKGROUND: Although combinations of antibiotics and antisecretory drugs are useful for treatment of Helicobacter pylori infection, treatment failure is common. The aim of this study was to evaluate the relation between pretreatment antibiotic resistance and outcome by using six different treatment regimens for H. pylori infection. PATIENTS AND METHODS: Three hundred sixty-nine consecutive H. pylori-infected patients with dyspeptic symptoms were enrolled in three consecutive randomized, controlled, single-center clinical trials: trial A, 128 patients; trial B, 125 patients; trial C, 116 patients. Treatments consisted of (A) a 15-day course of dual therapy (omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, or clarithromycin, 500 mg tid) (OA vs OC); (B) a 7-day triple therapy of omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, and amoxicillin, 1,000 mg bid, or clarithromycin, 500 mg tid (OMA vs OMC); or (C) omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, plus tetracycline, 500 mg qid, or doxycycline, 100 mg tid (OMT vs OMD). Diagnostic endoscopy was made in all patients before and 5 to 6 weeks after therapy. Six biopsies were taken from each patient for histology, rapid urease test, and H. pylori culture; antibiotic susceptibility testing was performed using the E-test method. RESULTS: Overall cure rates were poor for both dual therapies OA and OC (38% and 37%, respectively) and for triple therapies OMA, OMC, and OMD (57%, 55%, and 58%, respectively). The OMT combination was successful in 91% (95% confidence interval [CI], 80.4%-97%). Metronidazole resistance was present in 29.7% (95% CI, 24%-35%), amoxicillin resistance was present in 26% (95% CI, 21%-32%), clarithromycin resistance was present in 23.1% (95% CI, 18%-29%), tetracycline resistance was present in 14% (95% CI, 10%-20%), and doxycycline resistance was present in 33.3% (95% CI, 21%-47%). Antibiotic resistance markedly reduced the cure rates and accounted for most of the poor results with the triple therapies: 89% versus 23%; 77% versus 26%; 100% versus 60%; and 67% versus 23% for OMC, OMA, OMT, and OMD, respectively. OMT appeared to be the best because of the high success rate with metronidazole-resistant H. pylori (71%) and in low-level tetracycline resistance. CONCLUSIONS: Pretreatment antibiotic-resistant H. pylori can, in part, explain the low cure rate of the infection and the variability in outcome in reported trials.

Amoxycillin resistance is one reason for failure of amoxycillin-omeprazole treatment of Helicobacter pylori infection.

BACKGROUND: The efficacy of omeprazole and amoxycillin dual therapy to treat Helicobacter pylori infection has been inconsistent, suggesting the presence of host or bacterial factors influencing treatment success. The aim of this study was to assess the role of pre-treatment amoxycillin resistance in the efficacy of omeprazole and amoxycillin dual therapy. METHODS: We studied 43 consecutive dyspeptic patients with H. pylori infection. Pre-treatment H. pylori infection was established by the combination of positive rapid urease test, culture and histology. Amoxycillin susceptibility testing was performed by an Epsilometer test (E-test) method and amoxycillin resistance was defined as minimum inhibitory concentration greater than 8 microg/mL. Patients received 20 mg omeprazole twice daily for 28 days and amoxycillin 1000 mg twice daily for 2 weeks. Adverse effects were documented using a questionnaire. H. pylori status was reassessed 6-8 weeks after the end of treatment by rapid urease testing and histological examination of gastric biopsies. RESULTS: Forty-two dyspeptic patients completed the study, and one patient dropped out. H. pylori infection was cured in 2 3 of 42 patients (55%). The cure rate was higher in patients harbouring amoxycillin-sensitive organisms than in those with resistant strains: 66% (19/29) vs. 31% (4/13), respectively (P = 0.049). No significant differences in cure rates were evident in relation to age, sex, smoking habits or compliance. CONCLUSIONS: The effectiveness of amoxycillin-omeprazole dual therapy was greatly reduced in the presence of pre-treatment amoxycillin-resistant H. pylori. The success rate in patients with amoxycillin-sensitive H. pylori was only 66%, suggesting the presence of additional factors affecting the efficacy of this therapy.

IS200 fingerprint of Salmonella enterica serotype Typhimurium human strains isolated in Sardinia.

A collection of Salmonella enterica serotype Typhimurium human strains isolated in Northern Sardinia (Italy) was examined for the insertion sequence IS200, phage type, antibiotic profile, ribotyping polymorphisms and plasmid profile. All clinical isolates studied contained from 4 to 10 copies of the IS200 element. IS200 permitted to discriminate Typhimurium strains and to identify five IS200 types, some of them circulating in Sardinia at least since 1900. Strains belonging to phage DT104 predominated and correlated with a specific IS200 pattern.

Comparative in vitro activity of cefodizime and other antibiotics against pathogens recently isolated in Italy.

In the present study we tested the susceptibility to cefodizime on 1,985 selected nosocomial pathogens isolated in five laboratories. Moreover, we evaluated the epidemiology of the resistance of the tested strains to cefodizime and to other antibiotics clinically available in Italy. The susceptibility to cefodizime was determined with both MIC (microdilution method) and the agar diffusion method (Kirby-Bauer). The Kirby-Bauer method was used to compare the antibiotics. Cefodizime was equivalent in activity to ceftazidime and ceftriaxone and was more active than piperacillin and amoxicillin + clavulanic acid. The activity of gentamicin (where tested) was generally comparable to that of cefodizime; ciprofloxacin had lower percentages of resistance against some species of Enterobacteriaceae and staphylococci.