Reduced or modified dietary fat for preventing cardiovascular disease

BACKGROUND: Reduction or modification of dietary fat can improve total cholesterol levels, but may also have a variety of effects, both positive and negative, on other cardiovascular risk factors. OBJECTIVES: The aim of this systematic review was to assess the effect of reduction or modification of dietary fats on total and cardiovascular mortality and cardiovascular morbidity over at least 6 months, using all available randomized clinical trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE, CAB Abstracts, CVRCT registry and related Cochrane Groups' trial registers were searched through spring 1998, SIGLE to January 1999. Trials known to experts in the field and biographies were included through May 1999. SELECTION CRITERIA: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) healthy adult humans, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Inclusion decisions were duplicated, disagreement resolved by discussion or a third party. DATA COLLECTION AND ANALYSIS: Rate data were extracted by two independent reviewers and meta-analysis performed using random effects methodology. Meta-regression and funnel plots were used. MAIN RESULTS: Twenty seven studies were included (40 intervention arms, 30,901 person-years). There was no significant effect on total mortality (rate ratio 0.98, 95% CI 0.86 to 1.12), a trend towards protection form cardiovascular mortality (rate ratio 0.91, 95% CI 0.77 to 1.07), and significant protection from cardiovascular events (rate ratio 0.84, 95% CI 0.72 to 0.99). The latter became non-significant on sensitivity analysis. Trials where participants were involved for more than 2 years showed significant reductions in the rate of cardiovascular events and a suggestion of protection from total mortality. The degree of protection from cardiovascular events appeared similar in high and low risk groups, but was statistically significant only in the former. REVIEWER'S CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk in trials longer than two years. Lifestyle advice to all those at high risk of cardiovascular disease (especially where statins are unavailable or rationed), and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates

Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan

Integrated control of neglected tropical diseases (NTDs) is being scaled up in a number of developing countries, because it is thought to be more cost-effective than stand-alone control programmes. Under this approach, treatments for onchocerciasis, lymphatic filariasis (LF), schistosomiasis, soil-transmitted helminth (STH) infection, and trachoma are administered through the same delivery structure and at about the same time. A pre-requisite for implementation of integrated NTD control is information on where the targeted diseases are endemic and to what extent they overlap. This information is generated through surveys that can be labour-intensive and expensive. In Southern Sudan, all of the above diseases except onchocerciasis require further mapping before a comprehensive integrated NTD control programme can be implemented. To determine where treatment for which disease is required, integrated surveys were conducted for schistosomiasis, STH infection, LF, and loiasis, throughout one of ten states of the country. Our results show that treatment is only required for urinary schistosomiasis and STH in a few, yet separate, geographical area. This illustrates the importance of investing in disease mapping to minimize overall programme costs by being able to target interventions. Integration of survey methodologies for the above disease was practical and efficient, and minimized the effort required to collect these data

Comparative Field Evaluation of Combinations of Long-Lasting Insecticide Treated Nets and Indoor Residual Spraying, Relative to Either Method Alone, for Malaria Prevention in an Area where the main Vector is Anopheles Arabiensis.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are commonly used together in the same households to improve malaria control despite inconsistent evidence on whether such combinations actually offer better protection than nets alone or IRS alone. Comparative tests were conducted using experimental huts fitted with LLINs, untreated nets, IRS plus untreated nets, or combinations of LLINs and IRS, in an area where Anopheles arabiensis is the predominant malaria vector species. Three LLIN types, Olyset®, PermaNet 2.0® and Icon Life® nets and three IRS treatments, pirimiphos-methyl, DDT, and lambda cyhalothrin, were used singly or in combinations. We compared, number of mosquitoes entering huts, proportion and number killed, proportions prevented from blood-feeding, time when mosquitoes exited the huts, and proportions caught exiting. The tests were done for four months in dry season and another six months in wet season, each time using new intact nets. All the net types, used with or without IRS, prevented >99% of indoor mosquito bites. Adding PermaNet 2.0® and Icon Life®, but not Olyset® nets into huts with any IRS increased mortality of malaria vectors relative to IRS alone. However, of all IRS treatments, only pirimiphos-methyl significantly increased vector mortality relative to LLINs alone, though this increase was modest. Overall, median mortality of An. arabiensis caught in huts with any of the treatments did not exceed 29%. No treatment reduced entry of the vectors into huts, except for marginal reductions due to PermaNet 2.0® nets and DDT. More than 95% of all mosquitoes were caught in exit traps rather than inside huts. Where the main malaria vector is An. arabiensis, adding IRS into houses with intact pyrethroid LLINs does not enhance house-hold level protection except where the IRS employs non-pyrethroid insecticides such as pirimiphos-methyl, which can confer modest enhancements. In contrast, adding intact bednets onto IRS enhances protection by preventing mosquito blood-feeding (even if the nets are non-insecticidal) and by slightly increasing mosquito mortality (in case of LLINs). The primary mode of action of intact LLINs against An. arabiensis is clearly bite prevention rather than insecticidal activity. Therefore, where resources are limited, priority should be to ensure that everyone at risk consistently uses LLINs and that the nets are regularly replaced before being excessively torn. Measures that maximize bite prevention (e.g. proper net sizes to effectively cover sleeping spaces, stronger net fibres that resist tears and burns and net use practices that preserve net longevity), should be emphasized