The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature

Background: Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. Methods: A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. Results: Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. Conclusions: Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy

Existing data sources for clinical epidemiology: The pharmo database network

The PHARMO Database Network provides a unique opportunity to gain insight in the complete patient journey and healthcare in the Netherlands. The PHARMO Database Network is a population-based network of electronic healthcare databases and combines anonymous data from different primary and secondary healthcare settings in the Netherlands. Healthcare settings include general practitioners, out-patient and in-patient pharmacies, hospitals and clinical laboratories. Furthermore, databases are linked with external registries suc

Spillover of interpersonal conflicts from work into nonwork: A daily diary study

This study among a heterogeneous sample of employees expands the Job-Demands (JD-R) theory by examining how interpersonal conflicts at work -task and relationship conflictspillover into the non-work domain on a daily basis. We hypothesized that daily personal resources can buffer the daily negative spillover of interpersonal conflicts from work into the non-work domain. A total of 113 employees (N = 565 occasions) filled in a daily diary questionnaire in the evening before bedtime over five consecutive working days. Results of multi-level analysis showed that the presence of daily personal resources is essential in order to buffer the spillover of interpersonal conflict at work to the non-work domain. Specifically, on days that employees were not very optimistic or resilient, interpersonal conflicts resulted in higher strain-based work-life conflict experiences. These findings contribute to the JD-R theory and show how the unfavorable effects of daily interpersonal conflicts in the work domain may be avoided in the non-work domain through enhancing personal resources. We discuss the implications for theory and practice

Risk Factors for Tremor in a Population of Patients with Severe Mental Illness:An 18-year Prospective Study in a Geographically Representative Sample (The Curacao Extrapyramidal Syndromes Study XI)

BACKGROUND: The aim was to assess incidence, prevalence and risk factors of medication-induced tremor in African-Caribbean patients with severe mental illness (SMI).METHOD: A prospective study of SMI patients receiving care from the only mental health service of the previous Dutch Antilles. Eight clinical assessments, over 18 years, focused on movement disorders, medication use, and resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled with logistic regression for both current (having) tremor and for tremor at the next time point (developing). The latter used a time-lagged design to assess medication changes prior to a change in tremor state.RESULTS: Yearly tremor incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third of patients displayed tremor during the study. Of the patients, 5.2% had AT with 25% of cases persisting to the next time point, while 17.1% of patients had RT of which 65.3% persisted. When tremor data were examined in individual patients, they often had periods of tremor interspersed with periods of no tremor. Having RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03-1.11), sex (OR=0.17 for males; 0.05-0.78), cocaine use (OR=10.53; 2.22-49.94), dyskinesia (OR=0.90; 0.83-0.97), and bradykinesia (OR=1.16; 1.09-1.22). Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80-25.63), with previous RT severity (OR=1.22; 1.05-1.41), and higher anticholinergic load (OR= 1.24; 1.08-1.43). Having AT was associated with tremor-inducing medication (OR= 4.54; 1.90-10.86), cocaine use (OR=14.04; 2.38-82.96), and bradykinesia (OR=1.07; 1.01-1.15). Developing AT was associated with, previous AT severity (OR=2.62 per unit; 1.64-4.18) and tremor reducing medication (OR=0.08; 0.01-0.55).CONCLUSIONS: Long-stay SMI patients are prone to developing tremors, which show a relapsing-remitting course. Differentiation between RT and AT is important as risk factors differ and they require different prevention and treatment strategies.</p

CoA-dependent activation of mitochondrial acyl carrier protein links four neurodegenerative diseases

PKAN, CoPAN, MePAN, and PDH-E2 deficiency share key phenotypic features but harbor defects in distinct metabolic processes. Selective damage to the globus pallidus occurs in these genetic neurodegenerative diseases, which arise from defects in CoA biosynthesis (PKAN, CoPAN), protein lipoylation (MePAN), and pyruvate dehydrogenase activity (PDH-E2 deficiency). Overlap of their clinical features suggests a common molecular etiology, the identification of which is required to understand their pathophysiology and design treatment strategies. We provide evidence that CoA-dependent activation of mitochondrial acyl carrier protein (mtACP) is a possible process linking these diseases through its effect on PDH activity. CoA is the source for the 4 '-phosphopantetheine moiety required for the posttranslational 4 '-phosphopantetheinylation needed to activate specific proteins. We show that impaired CoA homeostasis leads to decreased 4 '-phosphopantetheinylation of mtACP. This results in a decrease of the active form of mtACP, and in turn a decrease in lipoylation with reduced activity of lipoylated proteins, including PDH. Defects in the steps of a linked CoA-mtACP-PDH pathway cause similar phenotypic abnormalities. By chemically and genetically re-activating PDH, these phenotypes can be rescued, suggesting possible treatment strategies for these diseases

Species-specific metabolic reprogramming in human and mouse microglia during inflammatory pathway induction

Metabolic reprogramming is a hallmark of the immune cells in response to inflammatory stimuli. This metabolic process involves a switch from oxidative phosphorylation (OXPHOS) to glycolysis or alterations in other metabolic pathways. However, most of the experimental findings have been acquired in murine immune cells, and little is known about the metabolic reprogramming of human microglia. In this study, we investigate the transcriptomic, proteomic, and metabolic profiles of mouse and iPSC-derived human microglia challenged with the TLR4 agonist LPS. We demonstrate that both species display a metabolic shift and an overall increased glycolytic gene signature in response to LPS treatment. The metabolic reprogramming is characterized by the upregulation of hexokinases in mouse microglia and phosphofructokinases in human microglia. This study provides a direct comparison of metabolism between mouse and human microglia, highlighting the species-specific pathways involved in immunometabolism and the importance of considering these differences in translational research.</p

High-resolution dietary reconstruction of victims of the 79 CE Vesuvius eruption at Herculaneum by compound-specific isotope analysis.

The remains of those who perished at Herculaneum in 79 CE offer a unique opportunity to examine lifeways across an ancient community who lived and died together. Historical sources often allude to differential access to foodstuffs across Roman society but provide no direct or quantitative information. By determining the stable isotope values of amino acids from bone collagen and deploying Bayesian models that incorporate knowledge of protein synthesis, we were able to reconstruct the diets of 17 adults from Herculaneum with unprecedented resolution. Significant differences in the proportions of marine and terrestrial foods consumed were observed between males and females, implying that access to food was differentiated according to gender. The approach also provided dietary data of sufficient precision for comparison with assessments of food supply to modern populations, opening up the possibility of benchmarking ancient diets against contemporary settings where the consequences for health are better understood

Blink rate is associated with drug-induced parkinsonism in patients with severe mental illness, but does not meet requirements to serve as a clinical test:The Curacao extrapyramidal syndromes study XIII

BACKGROUND: Drug-induced parkinsonism (DIP) has a high prevalence and is associated with poorer quality of life. To find a practical clinical tool to assess DIP in patients with severe mental illness (SMI), the association between blink rate and drug-induced parkinsonism (DIP) was assessed. METHODS: In a cohort of 204 SMI patients receiving care from the only mental health service of the previous Dutch Antilles, blink rate per minute during conversation was assessed by an additional trained movement disorder specialist. DIP was rated on the Unified Parkinson's Disease Rating Scale (UPDRS) in 878 assessments over a period of 18 years. Diagnostic values of blink rate were calculated. RESULTS: DIP prevalence was 36%, average blink rate was 14 (standard deviation (SD) 11) for patients with DIP, and 19 (SD 14) for patients without. There was a significant association between blink rate and DIP (p < 0.001). With a blink rate cut-off of 20 blinks per minute, sensitivity was 77% and specificity was 38%. A 10% percentile cut-off model resulted in an area under the ROC curve of 0.61. A logistic prediction model between dichotomous DIP and continuous blink rate per minute an area under the ROC curve of 0.70. CONCLUSIONS: There is a significant association between blink rate and DIP as diagnosed on the UPDRS. However, blink rate sensitivity and specificity with regard to DIP are too low to replace clinical rating scales in routine psychiatric practice. TRIAL REGISTRATION: The study was started over 20 years ago in 1992, at the time registering a trial was not common practice, therefore the study was never registered