Established and emerging vascular risk factors and the development of aortic stenosis: an opportunity for prevention?

Background: Aortic stenosis (AS) is the commonest valvular heart disease in the developed world. It is becoming increasingly accepted that the pathogenesis of AS and of its preceding abnormalities, aortic valve sclerosis (AVS) and aortic valve calcification (AVC), shares many characteristics with the atherosclerotic process. Objective: To assess the contribution of established and emerging vascular risk factors in the development of AS and to evaluate the potential of pharmacological intervention to modify the natural history of AS. Methods: We reviewed the epidemiological data that link AS and atherosclerosis and studies of vasculoprotective agents in patients with AS. Results/conclusions: AS, AVS and AVC share many common risk factors with atherosclerosis and are possible markers of preclinical vascular disease. Statins appear to delay the progression of AS. However, more studies are needed before introducing such pharmacologic treatment for AS. The future may point towards targeted prevention of AS.     

Diabetes mellitus as a risk factor for cancer: stress or viral etiology?

Diabetes mellitus (DM) is a metabolic disorder. Currently over 230 million patients demonstrate already an epidemic scale of the disease. It is a lifelong progressive disease with a high mortality worldwide: every 10 seconds one patient dies on DM-related consequences. Whereas cardio-vascular complications are well-known for DM, it is relatively new consideration that diabetic patients are highly predisposed to cancer. Particularities of molecular pathomechanisms of cancer in diabetes are currently largely unclear. Disturbed glucose/insulin homeostasis is DM-specific stress factor resulting in increased production of Reactive Oxygen Species (ROS) and oxidative damage to chromosomal and mitochondrial DNA frequently observed in diabetic patients. Long-term accumulation of DNA mutations is well-acknowledged as triggering cancer. DNA-repair is highly energy consuming process which provokes increased mitochondrial activity. Particularly dangerous is a provoked activity of damaged mitochondria which leads to the "vicious circle" lowing energy supply and potentiating ROS production. Mitochondrial dysfunction is the well-acknowledged risk factor for neuro/degenerative diseases--one of possible pathomechanisms for various complications developed secondary to diabetes. At the same time, mitochondrial dysfunction might be implicated in pathomechanisms of diabetes-provoked cancer. There is a growing body of evidence that DM predisposes to almost all cancer types with some particular preferences. Frequently suffering from compromised immune response, diabetic patients is high-risk group for infectious disorders including viral infections. In its turn, viral infections are known to be implicated in cancer pathology. This review considers both stress and viral infections as possible etiology of cancer in diabetes.     

Do adolescent delinquency and problem drinking share psychosocial risk factors? A literature review

Despite the prevalence and damaging effects of adolescent problem drinking, relative to delinquency, far less research has focused on drinking using an integrated theoretical approach. The aim of the current research was to review existing literature on psychosocial risk factors for delinquency and problem drinking, and explore whether integrating elements of social learning theory with an established psychosocial control theory of delinquency could explain adolescent problem drinking. We reviewed 71 studies published post-1990 with particular focus on articles that empirically researched risk factors for adolescent problem drinking and delinquency in separate and concurrent studies and meta-analytic reviews. We found shared risk factors for adolescent delinquency and problem drinking that are encompassed by an extension of psychosocial control theory. The potential of an extended psychosocial control theory providing a parsimonious theoretical approach to explaining delinquency, problem drinking and other adolescent problem behaviours, along with suggestions for future investigations, is discussed.     

A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient?

The field of erectile dysfunction (ED) has been revolutionised over the last two decades. Several treatment options are available today, most of which are associated with high efficacy rates and favourable safety profiles. A MEDLINE search was undertaken in order to evaluate all currently available data on treatment modalities for ED. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first-choice of most physicians and patients for the treatment of ED. PDE5 inhibitors have differences in their pharmacological profiles, the most obvious being the long duration of action of tadalafil, but there are no data supporting superiority for any one of them in terms of efficacy or safety. Sublingual apomorphine has limited efficacy compared with the PDE5 inhibitors, and its use is limited to patients with mild ED. Treatment failures with oral drugs may be due to medication, clinician and patient issues. The physician needs to address all of these issues in order to identify true treatment failures. Patients who are truly unresponsive to oral drugs may be offered other treatment options.Intracavernous injections of alprostadil alone, or in combination with other vasoactive agents (papaverine and phentolamine), remain an excellent treatment option, with proven efficacy and safety over time. Topical pharmacotherapy is appealing in nature, but currently available formulations have limited efficacy. Vacuum constriction devices may be offered mainly to elderly patients with occasional intercourse attempts, as younger patients show limited preference because of the unnatural erection that is associated with this treatment modality. Penile prostheses are generally the last treatment option offered, because of invasiveness, cost and non-reversibility; however, they are associated with high satisfaction rates in properly selected patients.All treatment options are associated with particular strengths and weaknesses. A patient-centred approach based on patient needs and expectations is necessary for the management of ED. The clinician must educate the patient and provide a supportive environment for shared decision making. The management strategy must be supplemented by careful follow-up in order to identify changes in patient health and relationship/emotional status that may necessitate treatment optimisation.     

“Technophilia”: A new risk factor for electronic cigarette use among early adolescents?

PurposeDevelop and validate a scale that measures Technophilia (positive orientation toward new technology) and use it to address orientation toward new technologies to explain e-cigarette trial and adoption, especially in relatively low risk adolescents.MethodsSurvey data were obtained from students of the three largest cities in Mexico (n = 8123). We developed eight questions involving access, use and pleasure from different electronic media to measure technophilia. Exploratory factor analysis (EFA) was conducted. Linear GEE models were used when regressing technophilia on covariates. When regressing e-cigarette and conventional cigarette trial and use, logistic GEE models were used. Finally, we used multinomial logistic regression to evaluate the associations between technophilia and e-cigarettes as the first tobacco product.ResultsTechnophilia were correlated with theoretically-related variables. Unadjusted and adjusted models regressing e-cigarette trial and use indicated that students in the highest quartile for technophilia were more likely to have tried e-cigarettes compared with the lowest quartile (AOR_{Q4 vs Q1} = 1.36, 95% CI 1.14–1.62). Technophilia was not independently associated with current e-cigarette use in adjusted models. Students with higher technophilia were more likely to have first tried e-cigarettes in both crude and adjusted models (AOR_Q4vQ1 = 1.66, 95% CI 1.20–2.31; AOR_Q3vQ1 = 1.43, 95% CI 1.02–2.01). Technophilia did not have a statistically significant, independent association with first use of other tobacco products.ConclusionThis study suggests that technophilia is associated with trial of e-cigarettes among youth. The measure we developed appears useful for understanding why some youth are open to trying novel, technologically oriented ways to consume nicotine.     

Is complicated grief a risk factor for substance use? A comparison of substance-users and normative grievers

Background: There are no studies to date which have examined complicated grief (CG) symptomatology in substance use disorder (SUD) populations specifically. This study aimed to determine if the presence of symptoms of CG is more frequent among drug dependent patients than a control group and identify which variables could be associated with the symptomatology of CG.

Method: Sociodemographic variables, drug and bereavement related characteristics, CG symptomatology and perceived social support were examined in a sample of 196 bereaved SUD patients (78.1% men). The control group was formed by 100 bereaved non-addicted participants (73% men). A multiple linear regression analysis was conducted to identify which variables were associated with symptoms of CG.

Results: The presence of symptoms of CG among SUD patients was 34.2%, in comparison to 5% in the control group. Respondents with a higher CG symptomatology include: those being widowed (β=?0.165), those who had lost a sibling (β?=?0.253), those who had experienced a traumatic death (β?=?0.158), those without working status (β=?0.005). By contrast, being from the control group (β=??0.157), reporting secondary education (β?=??0.201) and perceived social support (β?=??0.146) were found to be protective factors.

Conclusions: These findings highlight the importance of diagnosing and treating those bereaved individuals with SUD who appear to be particularly vulnerable to develop CG symptomatology.     

Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon?

A case–control study was conducted to examine whether occupational or environmental exposures, particularly to heavy metals, are associated with male infertility in Lebanon, a war-torn country with a history of environmental degradation. Seventy-four infertile cases and 76 fertile controls were selected from 2 major fertility clinics in Beirut. Data collection involved risk-factor interviews, semen analysis, and blood collection for heavy metal analysis. Multiple regression analysis showed that men with reported occupational exposures were twice as likely to be infertile as unexposed men. However, none of the subcategories of infertile men (based on semen analysis results) had significantly higher whole blood concentrations of heavy metals when compared to fertile controls. Blood concentrations were well within the range for referent populations of healthy individuals. Thus, despite Lebanon's poor record of occupational and environmental stewardship, exposure to metal pollutants does not appear to represent an important risk factor for male infertility.     

A prospective study of risk drinking: at risk for what?

Data from two waves of a nationally representative U.S. population sample were used to link frequency of risk drinking in the year preceding the Wave 1 interview with the incidence or occurrence of various adverse outcomes in the approximately 3-year-period between the two interviews (n=22,122 Wave 1 drinkers who were reinterviewed at Wave 2). Risk drinking was defined as consuming the equivalent of 5+ standard drinks in a day for men and the equivalent of 4+ standard drinks in a day for women. Controls included sociodemographic and health characteristics, mean quantity of drinks consumed on risk drinking days and average volume of intake on non-risk drinking days. The odds of nonhierarchical alcohol abuse and dependence, initiation of smoking and incidence of nicotine dependence were increased at all frequencies of risk drinking and showed a fairly continuous increase in magnitude with increasing frequency, reaching OR of 3.03-7.23 for daily/near daily risk drinking. The incidence of liver disease was strongly increased among weekly or more frequent risk drinkers (OR=2.78-4.76). The odds of social harm and drug use were increased among daily/near daily risk drinkers (OR=1.61-2.54), and the likelihood of drivers license revocation showed near-significant increases at all frequencies of risk drinking. Frequency of risk drinking interacted with volume of intake on non-risk drinking days in predicting alcohol abuse and illicit drug use and with duration of drinking in predicting alcohol dependence. Risk drinking poses a threat of many types of harm, both directly and indirectly through its association with smoking initiation and nicotine dependence. These findings have illustrative value for prevention programs, and they indicate that frequent risk drinking is a strong marker for alcoholism.     

Emerging drug targets for Aβ and tau in Alzheimer’s disease: a systematic review

Aims

Currently, treatment for Alzheimer’s disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD.

Methods

A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group 1. Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence.

Results

The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration.

Conclusions

There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition.