Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, largely manifested as central nervous system (CNS) disorders. The principal site of manifestations in the mouse model is the fetal brain's neural progenitor cell (NPC)-rich subventricular zone. Our previous human NPC studies found these cells to be fully permissive for HCMV and a useful in vitro model system. In continuing work, we observed that under culture conditions favoring maintenance of multipotency, infection caused NPCs to quickly and abnormally differentiate. This phenotypic change required active viral transcription. Whole-genome expression analysis found rapid downregulation of genes that maintain multipotency and establish NPCs' neural identity. Quantitative PCR, Western blot, and immunofluorescence assays confirmed that the mRNA and protein levels of four hallmark NPC proteins (nestin, doublecortin, sex-determining homeobox 2, and glial fibrillary acidic protein) were decreased by HCMV infection. The decreases required active viral replication and were due, at least in part, to proteasomal degradation. Our results suggest that HCMV infection causes in utero CNS defects by inducing both premature and abnormal differentiation of NPCs.Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system (CNS). Primary infection during pregnancy poses a 30 to 40% risk of intrauterine transmission, with severe adverse outcomes more likely if the infection occurs within the first half of gestation (46). Each year, approximately 1% of all newborns are congenitally infected with HCMV. Approximately 5 to 10% of these infants manifest signs of serious neurological defects at birth, including deafness, mental retardation, blindness, microencephaly, hydrocephalus, and cerebral calcification (2,4,65). In addition, 10 to 15% of congenitally infected infants who are asymptomatic at birth subsequently develop brain disorders such as sensorineural hearing loss (12, 47, 52). Moreover, accumulating evidence suggests that more subtle changes in human brain development, such as autism and language development, may be related to congenital HCMV infection (68,76,77).Although HCMV can infect a wide range of tissues in vivo (61), the fetal brain is the principal site of the deleterious manifestations of infection. It has been suggested that the severity of neuropathological changes and clinical outcomes may be associated with the stage of CNS development at which congenital infection occurs, with early-gestation infections producing more severe outcomes (3, 46). However, the mechanism of HCMV pathogenesis in the developing CNS remains poorly understood. Studies of HCMV in human subjects have obvious limitations; therefore, model systems of both in vitro and in vivo HCMV infections have been devised to provide insights into infection of the developing brain.Congenital infection studies have been performed principally with the mouse model. Studies of mice revealed that very ea...

Psoriasis is one of the prevalent skin conditions in the United States. This chronic condition has a significant negative impact on patients' quality of life. Psoriasis has been linked to the depression and suicidal tendencies in the patients. The costs associated with decrements in quality of life, lost productivity, and work absenteeism may be enormous, increasing overall costs associated with the disease management. This review attempts to outline different quality of life measures available for psoriasis and describes their use in studies examining patient reported outcomes associated with pharmacological interventions for psoriasis. Factors associated with quality of life in psoriasis patients are described. It further describes physician's role in the psoriasis management to improve patients' overall well-being.

Background Many countries, mainly high- and upper-middle income, have implemented human papillomavirus (HPV) vaccination programs, with 47 million women receiving the full course of vaccine (three doses) in 2014. To evaluate the potential impact of HPV vaccines in the reduction of HPV-related disease, we aimed to estimate the HPV type distribution and burden of anogenital and head and neck cancers attributable to HPV types (HPVs 16/18/31/33/45/52/58/6/11) included in currently licensed HPV vaccines. Methods In all, 18 247 formalin-fixed paraffin-embedded specimens were retrieved from 50 countries. HPV DNA detection and typing were performed with the SPF-10 PCR/DEIA/LiPA25 system. With the exception of cervical cancer, HPV DNA-positive samples were additionally subjected to HPV E6*I mRNA detection and/or p16INK4a immunohistochemistry. For cervical cancer, estimates were based on HPV DNA, whereas for other sites, estimates were based on HPV DNA, E6*I mRNA, and p16INK4a biomarkers. Results The addition of HPVs 31/33/45/52/58 to HPVs 16/18/6/11 in the nonavalent HPV vaccine could prevent almost 90% of cervical cancer cases worldwide. For other sites, the nonavalent HPV vaccine could prevent 22.8% of vulvar, 24.5% of penile, 60.7% of vaginal, 79.0% of anal cancers, 21.3% of oropharyngeal, 4.0% of oral cavity, and 2.7% of laryngeal cancer cases. Conclusions Our estimations suggest a potential impact of the nonavalent HPV vaccine in reducing around 90% of cervical cancer cases and a global reduction of 50% of all the cases at HPV-related cancer sites.

Maintenance of symptom control in Parkinson's disease (PD) requires continuous titration of medication and addition of multiple therapies over the course of the disease. Adherence to medication is vital to symptom control and key to maximizing the efficacy of existing therapies. However, adherence is compromised by a variety of factors, including motor symptoms, complex dosing regimens, multiple medications, and lack of patient/physician awareness of the impact and prevalence of suboptimal adherence. This retrospective, longitudinal cohort study assessed the prevalence of suboptimal adherence [measured as the medication possession ratio (MPR)] to PD medications, and its impact on the worsening of PD symptoms (measured as increase in monotherapy dose, augmentation of therapy, PD-related emergency department visit, or hospitalization), in a Medicare Health Maintenance Organization population in the United States. Irrespective of the MPR threshold chosen, a high percentage of patients were categorized as suboptimally adherent to their PD medications, and patients with suboptimal adherence to their PD medications had higher risks of worsening of PD symptoms, compared with those who were adherent. Increased awareness of both the magnitude and impact of suboptimal adherence to PD medications, coupled with dosage simplification and a unified effort by healthcare professionals and patients, may improve adherence to PD medications and ultimately improve symptom control.

This preliminary study finds that psoriasis is associated with a reduction in work productivity and social functioning; this may explain the relatively high cost of this disease on both a macro- and microeconomic level. As there was a lack of significant trends in this study, formal inferences are limited and further investigation is warranted.