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Introduction: Liquefied petroleum gas (LPG) is a clean cooking fuel that emits less household air pollution (HAP) than polluting cooking fuels (e.g. charcoal, wood). While switching from polluting fuels to LPG can reduce HAP and improve health, the impact of ‘stacking’ (concurrent use of polluting fuels and LPG) on adverse health symptoms (e.g. headaches, eye irritation, cough) among female cooks is uncertain. Methods: Survey data from the CLEAN-Air(Africa) study was collected on cooking patterns and health symptoms over the last 12 months (cough, wheezing, chest tightness, shortness of breath, eye irritation, headaches) from approximately 400 female primary cooks in each of three peri‑urban communities in sub-Saharan Africa: Mbalmayo, Cameroon; Obuasi, Ghana; and Eldoret, Kenya. Random effects Poisson regression, adjusted for socioeconomic and health-related covariates, assessed the relationship between primary and secondary cooking fuel type and self-reported health symptoms. Results: Among 1,147 participants, 10 % (n = 118) exclusively cooked with LPG, 45 % (n = 509) stacked LPG and polluting fuels and 45 % (n = 520) exclusively cooked with polluting fuels. Female cooks stacking LPG and polluting fuels had significantly higher odds of shortness of breath (OR 2.16, 95 %CI:1.04–4.48) compared with those exclusively using LPG. In two communities, headache prevalence was 30 % higher among women stacking LPG with polluting fuels (Mbalmayo:82 %; Eldoret:65 %) compared with those exclusively using LPG (Mbalmayo:53 %; Eldoret:33 %). Women stacking LPG and polluting fuels (OR 2.45, 95 %CI:1.29–4.67) had significantly higher odds of eye irritation than women cooking exclusively with LPG. Second-hand smoke exposure was significantly associated with higher odds of chest tightness (OR 1.92, 95 % CI:1.19–3.11), wheezing (OR 1.76, 95 % CI:1.06–2.91) and cough (OR 1.78, 95 %CI:1.13–2.80). Conclusions: In peri‑urban sub-Saharan Africa, women exclusively cooking with LPG had lower odds of several health symptoms than those stacking LPG and polluting fuels. Promoting a complete transition to LPG in these communities may likely generate short-term health benefits for primary cooks.

Abstract Background Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are delta retroviruses with similar genetic organization. Although both viruses immortalize T-cells in vitro, they exhibit distinct pathogenic potential in vivo. To search for possible differences in its expression strategy with respect to HTLV-1, we investigated the pattern of HTLV-2 expression in infected cell lines and peripheral blood mononuclear cells (PBMCs) from infected patients using splice site-specific quantitative RT-PCR. Findings A novel alternative splice acceptor site for exon 2 was identified; its usage in env transcripts was found to be subtype-specific. Time-course analysis revealed a two-phase expression kinetics in an infected cell line and in PBMCs of two of the three patients examined; this pattern was reminiscent of HTLV-1. In addition, the minus-strand APH2 transcript was mainly detected in the nucleus, a feature that was similar to its HTLV-1 orthologue HBZ. In contrast to HTLV-1, expression of the mRNA encoding the main regulatory proteins Tax and Rex and that of the mRNAs encoding the p28 and truncated Rex inhibitors is skewed towards p28/truncated Rex inhibitors in HTLV-2. Conclusion Our data suggest a general converging pattern of expression of HTLV-2 and HTLV-1 and highlight peculiar differences in the expression of regulatory proteins that might influence the pathobiology of these viruses.

Community-centered approaches can be effective ways to engage communities and improve their health and well-being. The Grange is a community-led, multifaceted, and dynamic intervention incorporating a community hub and garden, that took place in a small area of the North-West of England, characterized by high levels of deprivation and poor health. Activities have been defined, developed, and supported by residents to meet locally defined needs. This study used photovoice methods to explore residents' perceptions and experiences of this community-led intervention and any perceived impact on health, well-being, and community inclusion. Through photographs, semistructured interviews, a focus group discussion, and an exhibition, this study engaged intensively and creatively with a group of six residents. They identified positive and negative aspects related to The Grange and suggested recommendations that were directly communicated to policy makers during the photo-exhibition event. Participants reflected on various activities such as the community garden and the community shop. They also reflected on contextual factors and suggested that the culture of inclusivity and friendships associated with The Grange were more important to them than specific activities. This study demonstrated the value of using photovoice to: (1) explore residents' perceptions of community led interventions; and (2) meaningfully engage residents living in areas with high levels of deprivation. Public health practitioners should consider the use of photovoice: (1) in the evaluation of health interventions that take place in a complex and changing context; and (2) as a powerful tool to engage with members of the community, especially traditionally disadvantaged groups, to ensure that engagement about health, well-being, and social inclusion is meaningful.

Abstract Background Locally delivered, place-based public health interventions are receiving increasing attention as a way of improving health and reducing inequalities. However, there is limited evidence on their effectiveness. This umbrella review synthesises systematic review evidence of the health and health inequalities impacts of locally delivered place-based interventions across three elements of place and health: the physical, social, and economic environments. Methods Systematic review methodology was used to identify recent published systematic reviews of the effectiveness of place-based interventions on health and health inequalities (PROGRESS+) in high-income countries. Nine databases were searched from 1st January 2008 to 1st March 2020. The quality of the included articles was determined using the Revised Assessment of Multiple Systematic Reviews tool (R-AMSTAR). Results Thirteen systematic reviews were identified - reporting 51 unique primary studies. Fifty of these studies reported on interventions that changed the physical environment and one reported on changes to the economic environment. Only one primary study reported cost-effectiveness data. No reviews were identified that assessed the impact of social interventions. Given heterogeneity and quality issues, we found tentative evidence that the provision of housing/home modifications, improving the public realm, parks and playgrounds, supermarkets, transport, cycle lanes, walking routes, and outdoor gyms – can all have positive impacts on health outcomes – particularly physical activity. However, as no studies reported an assessment of variation in PROGRESS+ factors, the effect of these interventions on health inequalities remains unclear. Conclusions Place-based interventions can be effective at improving physical health, health behaviours and social determinants of health outcomes. High agentic interventions indicate greater improvements for those living in greater proximity to the intervention, which may suggest that in order for interventions to reduce inequalities, they should be implemented at a scale commensurate with the level of disadvantage. Future research needs to ensure equity data is collected, as this is severely lacking and impeding progress on identifying interventions that are effective in reducing health inequalities. Trial registration PROSPERO CRD42019158309

BackgroundGastrointestinal (GI) infections cause a significant public health burden worldwide and in the UK with evidence pointing to socio-economic inequalities, particularly among children. Qualitative studies can help us understand why inequalities occur and contribute to developing more effective interventions. This study had two aims: 1. Conduct a systematic review to determine the extent and nature of UK qualitative evidence on gastrointestinal infections; 2. Use meta-ethnography to examine the influences of the differing social contexts in which people live.MethodsMEDLINE, Scopus, Web of science, CINAHL and JSTOR were searched for UK qualitative studies engaging with the risk, diagnosis, management or consequences of gastrointestinal infections from 1980 to July 2019. Five reviewers were involved in applying inclusion and exclusion criteria, extracting and synthesising data (PROSPERO CRD 42017055157).ResultsSearches identified 4080 studies, 18 met the inclusion criteria. The majority (n = 16) contained data relating to the risk of gastrointestinal infection and these made up the main synthesis. The tenets of meta-ethnography were used to glean new understandings of the role of social and environmental contexts in shaping the risk of gastrointestinal infection, specifically with respect to foodborne GI illness. Three main explanations concerning risk emerged from the data: explanations of risk in the community were underpinned by understandings of 'bugs', dirt and where food comes from; risks were negotiated in households alongside diverse processes of decision making around food; and resources available to households shaped food practices.ConclusionThis systematic review highlights the scarcity of UK qualitative evidence examining gastrointestinal infections. Apart from risk, questions around diagnosis, management and consequences of illness were largely untouched. No studies investigated patterning by socio-economic status. Nevertheless, the meta-ethnography yielded wider contextual theories and explanations as to why people might not follow food hygiene guidance, giving pointers to the types of qualitative enquiry needed to develop more effective interventions.

Abstract Background Many interventions have been developed to promote respect and social inclusion among older people, but the evidence on their impacts on health has not been synthesised. This systematic review aims to appraise the state of the evidence across the quantitative and qualitative literature. Methods Eligible studies published between 1990 and 2015 were identified by scanning seven bibliographic databases using a pre-piloted strategy, searching grey literature and contacting experts. Studies were included if they assessed the impact (quantitatively) and/or perceived impact (qualitatively) of an intervention promoting respect and social inclusion on the physical or mental health of community-residing people aged 60 years and older. Titles and abstracts were screened for eligibility by one reviewer. A second reviewer independently screened a 10% random sample. Full texts were screened for eligibility by one reviewer, with verification by another reviewer. Risk of bias was assessed using standardised tools. Findings were summarised using narrative synthesis, harvest plots and logic models to depict the potential pathways to health outcomes. Results Of the 27,354 records retrieved, 40 studies (23 quantitative, 6 qualitative, 11 mixed methods) were included. All studies were conducted in high and upper middle-income countries. Interventions involved mentoring, intergenerational and multi-activity programmes, dancing, music and singing, art and culture and information-communication technology. Most studies (n = 24) were at high or moderate risk of bias. Music and singing, intergenerational interventions, art and culture and multi-activity interventions were associated with an overall positive impact on health outcomes. This included depression (n = 3), wellbeing (n = 3), subjective health (n = 2), quality of life (n = 2), perceived stress and mental health (n = 2) and physical health (n = 2). Qualitative studies offered explanations for mediating factors (e.g. improved self-esteem) that may lead to improved health outcomes and contributed to the assessment of causation. Conclusions Whilst this review suggests that some interventions may positively impact on the health outcomes of older people, and identified mediating factors to health outcomes, the evidence is based on studies with heterogeneous methodologies. Many of the interventions were delivered as projects to selected groups, raising important questions about the feasibility of wider implementation and the potential for population-wide benefits. Systematic review registration PROSPERO registration number CRD42014010107

This research looked into the effectiveness of a campaign at the Universiti Sains Malaysia for a compulsory ban on disposable plastics. Although there was high awareness of the "Say No to Plastic Bags" bags campaign, and moderate compliance on campus, we wondered whether a compulsory approach would maintain the desired behaviours off campus and over time. We surveyed a sample of 300 first-year students and conducted in-depth interviews after two years with eight students who were involved in the earlier survey. The impacts of the campaign were moderate based on the level of knowledge, attitude and practice of the students. The compulsory approach caused a minimal level of cognitive dissonance, inconsistent practice outside the campus and the possibility of discontinuation of practice in the long run, but the differences were not significant. Based on the follow-up interviews, the study concludes that knowledge alone is insufficient to motivate long-term behaviours. More important to maintain behaviour change is a strong positive attitude towards the issue and continuous support from family and friends. (Contains 4 tables and 3 notes.)

BACKGROUND: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.

To improve the well-being of young people in the province of Taranto (Italy), intervention research was performed to study the effects of sport and its fundamental role in the prevention of juvenile deviance. A questionnaire was administered to 174 subjects (aged 7 and 11), and data were collected that investigated the main areas of influence in the process of growth and harmonious development of the minors' personality structure in relation to sports practice. Sport is widely recognized as a means of disseminating and transmitting positive values such as solidarity, loyalty, respect for people and the rules; in addition, sport can create a suitable environment for promoting ease and well-being in youth. The obtained results showed that the presence of and intervention by experienced and trained figures in the sports field, such as sports science graduates, is essential. The performed research showed a significant change in the organization and function of the family and sports associations because they must respond to new educational needs arising from the current phase of social culture. Both have an enormous responsibility in the prevention of youth discomfort. The performed research indicates that in addition to the family, there is a growing need for institutional figures who are trained and well-prepared such as coaches and managers of sports associations. These figures, better if they have a degree in sports sciences, have a pedagogical and strategic value for the minors because they can positively influence the conditions of growth, evolution, and harmonious development, and contrast and prevent deviant behaviours in youth. [ABSTRACT FROM AUTHOR]

There is no standard physical exercise protocol that can guarantee adequate physical and working efficiency of police officers. However, integrated circuit training can be used to train more physical abilities by optimizing timing and promoting well-being and performance in job tasks. Therefore, the purpose of this preliminary study was to monitor and evaluate the physiological and perceptual impact of multifunctional tactical training (MTT) and to develop it as a specific method for increasing the physical and working abilities of the Mobile Units police officers. A total of 4 police officers (of different ages, seniority, and anthropometric characteristics) voluntarily participated in this study. They used the MTT method consisting of a series of multiple exercises that are specific and functional for the Mobile Units personnel and designed to develop strength, muscular endurance, cardiorespiratory endurance, speed, aerobic and anaerobic power, reaction time, coordination, dynamic balance, and agility. The MTT method was developed according to the principles of individualization, progressivity, variety and multilaterality of the load. Small tools and materials from riot gear were used. During the MTT session (approximately 40 min duration), the police officers' heart rate was constantly monitored, and the rate of perceived exertion was measured immediately before and after each execution of the circuit, which was performed three times. The obtained results show that MTT is a safe and effective method for training the cardiorespiratory system. In addition, functional exercises are necessary to prepare the police officers to efficiently perform tactical tasks while preventing the risk of injury. Further studies are needed to improve the MTT method with an objective of continuous physical-motor education among police officers. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a developmental disorder that affects communication and behaviour. Previously, multiple interventions were designed to improve social-emotional and executive functioning in children with ASD. However, to date, only a few studies have examined the role of martial arts on social dysfunction and executive functioning deficits in children with ASD. Therefore, this study examined the effects of a 12-week Karate training on social-emotional and executive functioning of children (8-11 years) with ASD. Twenty-eight children were matched into pairs based on age, gender, and autism severity, and randomly allocated into an intervention (n = 14) or waitlist control group (n = 14). The intervention group performed Kata techniques training two times per week (45 min). The intervention included typically-developing children that helped facilitate the social skills, and activities targeted to train specific domains of executive functions, namely behavioural inhibition, working memory, and cognitive flexibility. At baseline and after 12 weeks, parents assessed social skills and executive functioning respectively through the Social Skills Improvement System Rating Scale and Behaviour Rating Inventory of Executive Function. After 12-week, the intervention group showed greater socio-emotional competence such as communication, cooperation and engagement, better executive functioning ability such as cognitive flexibility, inhibitory control and working memory, and a lower aggressiveness, sadness, anxiety and hyperactivity compared to the control group (p< 0.01; large effect size). Since ASD is a broad economic and societal problem that affects individual, family, and community levels, Karate training should be considered by autism institutions to improve individual well-being and overall health. Key Words: working memory; cognitive flexibility; inhibitory control; social skills; behavioural problems. [ABSTRACT FROM AUTHOR]

In 2016, the government of Cameroon, a central African country heavily reliant on wood fuel for cooking, published a Masterplan for increasing primary use of LPG from 20% to 58% of households by 2035. Developed via a multi-sectoral committee with support from the Global LPG Partnership, the plan envisages a 400 million Euro investment program to 2030, focused on increasing LPG cylinder numbers, key infrastructure, and enhanced regulation. This case study describes the Masterplan process and investment proposals and draws on community studies and stakeholder interviews to identify factors likely to impact on the planned expansion of LPG use. [ABSTRACT FROM AUTHOR]

Summary: HBV eradication in chronic hepatitis B (CHB) subjects is rarely achieved with either nucleos(t)ide analogues (NA) or pegylated interferon (Peg‐IFN), which both have a limited effect in restoring immune responses. Thirty CHB subjects on long‐term treatment with tenofovir (TDF) and HBV suppression were enrolled and randomized 1:2 to either receive Peg‐IFN‐α‐2a add‐on therapy or continue TDF alone. We studied γδ T and iNKT frequency and function (by flow cytometry) at baseline, at 12 weeks and 12 weeks after the end of treatment. A higher reduction in qHBsAg occurred in the add‐on group compared with the NA group at W12 (P = .016) and at W24 (P = .012). A decline of qHBsAg ≥0.5 log10 at week 24 occurred in 4 of 10 patients in the add‐on arm and 1 of 20 in the NA arm, respectively (P = .03). HBsAg loss was seen in 20% of subjects in the add‐on group and in none of the NA group. Compared to HBV negative, CHB on TDF showed lower frequency of iNKT (P = .03) and γδ T cells (P = .03) as well as fewer γδ T cells expressing Vδ2 T‐cell receptors (P = .005). No changes in unconventional T‐cell frequency and function were shown in both add‐on and NA patients nor were differences detected between the two treatment groups. We report persistent impairment of unconventional T cells in CHB. Despite a greater qHBsAg decline of add‐on patients, our data failed to detect any effect of Peg‐IFN treatment on unconventional T cells. [ABSTRACT FROM AUTHOR]

Objectives Clinical trials of all-oral direct-acting antivirals ( DAAs) for chronic hepatitis C virus ( HCV) infection reported high response rates in HCV/ HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting. Methods In this prospective observational study, all the HCV-monoinfected and HCV/ HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy ( SVR12) and reported adverse events ( AEs) were evaluated. Resistance-associated variants ( RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure. Results One-hundred and nine patients (51 HCV-infected and 58 HCV/ HIV-coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (peg IFN/ RBV)-experienced. Thirty-six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV-infected and uninfected patients, respectively ( P = 0.44). The 4-week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort. Conclusions Treatment with all-oral DAA combinations of patients infected with HCV and with HCV/ HIV under real-life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to peg IFN/ RBV were not predictive of the response to all-oral DAAs. [ABSTRACT FROM AUTHOR]

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria, Background Micro RNAs (miRNAs) inhibit HIV‐1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. Here, we investigated the miRNA profile that discriminates different classes [...]

Urbanisation and population ageing have contributed to recognise cities as important settings for healthy ageing. This paper considers opportunities, challenges and solutions of using photovoice methods for exploring how individuals perceive their cities and the contribution this makes to their health. It focuses on one aspect of older people's experiences – respect and social inclusion, in the context of a community-based participatory research. Drawing on selected findings (participants' photographs, associated quotes and researchers' field notes), we provide an assessment of the suitability of photovoice methodology for the intended purpose. Four groups of older people (n=26; aged 60 years or more) from four contrasting geographical areas in Liverpool, UK, were recruited purposively. Participants photographed perceived positive and negative aspects of respect and social inclusion in the city, reflecting on the meanings of the photographs in individual (n=23) and group interviews (n=9). Thematic and content analysis was conducted using NVivo 10 software.The work reported here provides insights into how participants engage with the photovoice process; factors preventing taking photos of interest; and how photographs complement interviews and focus groups. The findings demonstrate that photovoice both facilitated the dissemination of personalised relevant knowledge, and encouraged critical dialogue between participants, and city stakeholders. Reported difficulties included photography of negative and social concepts, and anxiety when taking photographs due to (i) expectations of what is a ‘proper’ photograph, and (ii) the need to obtain consent from subjects. With preparation, training, and discussion of participants’ ideas not expressed through photographs, photovoice was well-suited to this topic, providing insights complementing other research methods. Through analysing the application of photovoice for exploring perceptions of respect and social inclusion in cities, our paper has identified potential issues and provides important recommendations for researchers on how photovoice methodology can be strengthened in exploring conditions for better health in the urban environment. Keywords: UK, Older people, Aging, Age-friendly city, Photovoice, Community-based participatory research

The potential of anaflatoxin B(1) (AnAFB(1)) conjugated to keyhole limpet hemocyanin (KLH) as a vaccine (AnAFB(1)-KLH) in controlling the carry over of the aflatoxin B(1) (AFB(1)) metabolite aflatoxin M(1) (AFM(1)) in cow milk is reported. AFB(1) is the most carcinogenic compound in food and foodstuffs amongst aflatoxins (AFs). AnAFB(1) is AFB(1) chemically modified as AFB(1)-1(O-carboxymethyl) oxime. In comparison to AFB(1), AnAFB(1) has proven to be non-toxic in vitro to human hepatocarcinoma cells and non mutagenic to Salmonella typhimurium strains. AnAFB(1)-KLH was used for immunization of cows proving to induce a long lasting titer of anti-AFB(1) IgG antibodies (Abs) which were cross reactive with AFB(1), AFG(1), and AFG(2). The elicited anti-AFB(1) Abs were able to hinder the secretion of AFM(1) into the milk of cows continuously fed with AFB(1). Vaccination of lactating animals with conjugated AnAFB(1) may represent a solution to the public hazard constituted by milk and cheese contaminated with AFs.

A 50-year-old man, pentathlete and fond of salmon fishing, after returning from Alaska was referred to our Division for an erythematous and indolent lesion on the right thigh gradually enlarging from the right knee to the right rear and the buttock.The patient was clinically diagnosed with figurate erythema. Laboratory analysis demonstrated a moderate leukocytosis and hypergammaglobulinemia, accompanied by serological markers of past contact with noted EBV and CMV.A “punch” biopsy of the edge of the lesion showed a superficial and deep perivascular and interstitial infiltrate of lymphocytes, eosinophiles and a few plasma cells, consistent with a borrelial infection. Lyme serology (IFI) suggested a questionable borderline positivity; subsequent investigations by ELISA and Western Blot were both positive, leading to the diagnosis of erythema chronicum migrans in course of borreliosis.The diagnosis was further confirmed by positive PCR for Borrelia burgdorferi sensu lato. The erythema resolved after a 2-week doxycycline treatment (2x100 mg die). The amplification product (16S rDNA gene) obtained from skin biopsy was sequenced using standard ABI technology, and confirmed the identification of a member of B. burgdorferi sensu lato (sl) complex. Since this sequence was not useful to identify the genospecies, further studies were conducted employing a nested PCR targeted on the internal transcribed spacer (ITS) of B. burgdorferi, following a protocol previously described (1). The ITS sequence showed 100% identity with B. afzelii, a species not reported from North America, thus prompting us to conclude that the patient was not infected by B. afzelii during the fishing trip in Alaska.

Objectives: Clinical trials of all-oral direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting., Methods: In this prospective observational study, all the HCV-monoinfected and HCV/HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy (SVR12) and reported adverse events (AEs) were evaluated. Resistance-associated variants (RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure., Results: One-hundred and nine patients (51 HCV-infected and 58 HCV/HIV-coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (pegIFN/RBV)-experienced. Thirty-six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV-infected and uninfected patients, respectively (P = 0.44). The 4-week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort., Conclusions: Treatment with all-oral DAA combinations of patients infected with HCV and with HCV/HIV under real-life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to pegIFN/RBV were not predictive of the response to all-oral DAAs., (© 2016 British HIV Association.)

The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono-infected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV mono-infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real-time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P<.01) that was not significantly different between the two study groups. Moreover, a significant decline in estimated glomerular filtration rate (eGFR) was observed from baseline (P<.01), and it was significantly greater in HBV mono-infected than co-infected patients (P=.03). The distribution of ABCC2, ABCC4 and ABCC10 genotypes among a subgroup of 34 patients did not show significant association with eGFR decline <90 mL/min per 1.73 m 2 . Although our findings showed a statistically significant decrease in eGFR with long-term use of TDF, its clinical impact seems to be modest. The role of genetic factors to identify patients at greater risk for developing tenofovir-induced renal toxicity needs to be further investigated., (© 2016 John Wiley & Sons Australia, Ltd.)

A phosphorylated peptide, named K40H, derived from the constant region of IgMs was detected in human serum by liquid chromatography coupled to high-resolution mass spectrometry. Synthetic K40H proved to exert a potent in vitro activity against fungal pathogens, and to inhibit HIV-1 replication in vitro and ex vivo. It also showed a therapeutic effect against an experimental infection by Candida albicans in the invertebrate model Galleria mellonella. K40H represents the proof of concept of the innate role that naturally occurring antibody fragments may exert against infectious agents, shedding a new light upon the posthumous role of antibodies and opening a new scenario on the multifaceted functionality of humoral immunity.

Complex drug-drug interactions have been reported with concurrent administration of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors (PIs), leading to relevant limitations of the therapeutic options for patients coinfected with hepatitis C virus (HCV) and HIV. However, little is known about the pharmacokinetics and drug interactions between TVR and antiretrovirals in HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1-coinfected patients with advanced liver fibrosis treated with TVR-based triple anti-HCV therapy. No significant differences were observed in the pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15 of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir declined below their minimum effective concentrations even in association with TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR exposure was seen in patients concomitantly given amprenavir versus those given atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion, this study highlighted the feasibility of maintaining the current antiretroviral regimen in HIV/HCV-coinfected patients, even when significant interactions with TVR are predictable, whenever a change of HIV PIs is not deemed appropriate., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

The potential of anaflatoxin B(1) (AnAFB(1)) conjugated to keyhole limpet hemocyanin (KLH) as a vaccine (AnAFB(1)-KLH) in controlling the carry over of the aflatoxin B(1) (AFB(1)) metabolite aflatoxin M(1) (AFM(1)) in cow milk is reported. AFB(1) is the most carcinogenic compound in food and foodstuffs amongst aflatoxins (AFs). AnAFB(1) is AFB(1) chemically modified as AFB(1)-1(O-carboxymethyl) oxime. In comparison to AFB(1), AnAFB(1) has proven to be non-toxic in vitro to human hepatocarcinoma cells and non mutagenic to Salmonella typhimurium strains. AnAFB(1)-KLH was used for immunization of cows proving to induce a long lasting titer of anti-AFB(1) IgG antibodies (Abs) which were cross reactive with AFB(1), AFG(1), and AFG(2). The elicited anti-AFB(1) Abs were able to hinder the secretion of AFM(1) into the milk of cows continuously fed with AFB(1). Vaccination of lactating animals with conjugated AnAFB(1) may represent a solution to the public hazard constituted by milk and cheese contaminated with AFs.

Background: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here., Methodology/principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains., Conclusions/significance: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.

We examined the efficacy and effect of HAART in HIV-1-infected men confronted with assisted fertilization procedures. We showed that HAART did not always reduce the HIV-1-RNA level in blood and semen compartments, and that a significant upward shift in mitochondrial DNA was observed in spermatozoa from a HAART-treated patient group compared with spermatozoa from HAART-untreated or HIV-1-uninfected groups (P < 0.001). These findings emphasize the negative role of HAART, but not of HIV-1 infection, in determining semen alterations.

Human T-cell lymphotropic virus (HTLV) type II has spread among intravenous drug users (IDUs), many of whom are coinfected with HIV-1. We have investigated the rate of HTLV-II infection in 3574 Italian IDUs screened for HIV-1, HTLV-I, and HTLV-II from 1986 to the present. HTLV-II proviral load was determined by a real-time polymerase chain reaction specifically designed for tax amplification. The frequency of HTLV-II infection was 6.7% among HIV-1-positive subjects and 1.1% among HIV-1-negative subjects (P < 0.0001). For examination of AIDS progression, a group of 437 HIV-1-monoinfected subjects and another group of 96 HIV-1/HTLV-II-coinfected subjects were monitored. Enrollees were matched at entry by CD4 cell counts and followed for an average of 13 years. HIV-1/HTLV-II coinfection was associated with older age (P < 0.0001) and higher CD4 (P < 0.0001) and CD8 (P < 0.001) cell counts compared with monoinfected IDUs. The number of long-term nonprogressors for AIDS was significantly higher (P < 0.0001) among coinfected patients (13 [13.5%] of 96 patients) than HIV monoinfected patients (5 [1.1%] of 437 patients), showing that HTLV-II exerts a protective role. An increased incidence of liver disease and hepatitis C virus positivity among coinfected IDUs was observed. Five coinfected subjects undergoing antiretroviral therapy showed a significant (P < 0.05) increase in HTLV-II proviral load concomitant to a decrease in HIV-1 viremia, suggesting that the treatment is ineffective against HTLV-II infection.