Measuring Psoriasis Severity at Home.

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.

Cancer Risks Associated With TP53 Pathogenic Variants: Maximum Likelihood Analysis of Extended Pedigrees for Diagnosis of First Cancers Beyond the Li-Fraumeni Syndrome Spectrum.

PURPOSE: Establishing accurate age-related penetrance figures for the broad range of cancer types that occur in individuals harboring a pathogenic germline variant in the TP53 gene is essential to determine the most effective clinical management strategies. These figures also permit optimal use of cosegregation data for classification of TP53 variants of unknown significance. Penetrance estimation can easily be affected by bias from ascertainment criteria, an issue not commonly addressed by previous studies. MATERIALS AND METHODS: We performed a maximum likelihood penetrance estimation using full pedigree data from a multicenter study of 146 TP53-positive families, incorporating adjustment for the effect of ascertainment and population-specific background cancer risks. The analysis included pedigrees from Australia, Spain, and United States, with phenotypic information for 4,028 individuals. RESULTS: Core Li-Fraumeni syndrome (LFS) cancers (breast cancer, adrenocortical carcinoma, brain cancer, osteosarcoma, and soft tissue sarcoma) had the highest hazard ratios of all cancers analyzed in this study. The analysis also detected a significantly increased lifetime risk for a range of cancers not previously formally associated with TP53 pathogenic variant status, including colorectal, gastric, lung, pancreatic, and ovarian cancers. The cumulative risk of any cancer type by age 50 years was 92.4% (95% CI, 82.2 to 98.3) for females and 59.7% (95% CI, 39.9 to 81.3) for males. Females had a 63.3% (95% CI, 35.6 to 90.1) cumulative risk of developing breast cancer by age 50 years. CONCLUSION: The results from maximum likelihood analysis confirm the known high lifetime risk for the core LFS-associated cancer types providing new risk estimates and indicate significantly increased lifetime risks for several additional cancer types. Accurate cancer risk estimates will help refine clinical recommendations for TP53 pathogenic variant carriers and improve TP53 variant classification.

PAPRIKA: A Question Bank for Assessing Psoriatic Arthritis Risk in Individuals of Diverse Ancestries.

OBJECTIVE: We aimed to create a question bank about clinical factors for predicting the diagnoses of psoriatic arthritis in patients with psoriasis of various ancestries and skin tones, which can be completed entirely by patients. METHODS: Utah Psoriasis Initiative participants without a psoriatic arthritis diagnosis at enrollment were observed for diagnosis during the study period. We inferred ancestry from exome sequencing data and performed Cox proportional hazards regression to identify clinical predictors of psoriatic arthritis in different ancestry groups. Based on results and literature review, we developed a question bank for assessing psoriatic arthritis risk among patients with psoriasis in various ancestries. RESULTS: Patient-reported untreated psoriasis induration and history of fingernail psoriasis were associated with psoriatic arthritis in participants of European and non-European ancestry. We developed the Psoriatic Arthritis Prediction and Identification Question Bank for Diverse Ancestries (PAPRIKA) version 1.0, which included questions regarding psoriasis characteristics, arthritis symptoms, comorbidities, family history, and demographics. PAPRIKA is accessible at http://bjfenglab.org/. CONCLUSION: The clinical features (untreated psoriasis induration and history of fingernail psoriasis) that can predict psoriatic arthritis in European individuals also work for non-European individuals. PAPRIKA can be used to gather psoriatic arthritis predictive data from patients with psoriasis without provider assistance and is relevant for patients across ancestries.

Spatiotemporal variation in the fecal microbiota of mule deer is associated with proximate and future measures of host health.

BACKGROUND: Mule deer rely on fat and protein stored prior to the winter season as an energy source during the winter months when other food sources are sparse. Since associated microorganisms ('microbiota') play a significant role in nutrient metabolism of their hosts, we predicted that variation in the microbiota might be associated with nutrient storage and overwintering in mule deer populations. To test this hypothesis we performed a 16S rRNA marker gene survey of fecal samples from two deer populations in the western United States before and after onset of winter. RESULTS: PERMANOVA analysis revealed the deer microbiota varied interactively with geography and season. Further, using metadata collected at the time of sampling, we were able to identify different fecal bacterial taxa that could potentially act as bioindicators of mule deer health outcomes. First, we identified the abundance of Collinsella (family: Coriobacteriaceae) reads as a possible predictor of poor overwintering outcomes for deer herds in multiple locations. Second, we showed that reads assigned to the Bacteroides and Mollicutes Order RF39 were both positively correlated with deer protein levels, leading to the idea that these sequences might be useful in predicting mule deer protein storage. CONCLUSIONS: These analyses confirm that variation in the microbiota is associated with season-dependent health outcomes in mule deer, which may have useful implications for herd management strategies.

Psoriasis Characteristics for the Early Detection of Psoriatic Arthritis.

OBJECTIVE: Delays in the diagnosis and treatment of psoriatic arthritis (PsA) are common. These delays contribute to impairments in quality of life and joint damage. This study aims to calculate the incidence rate of PsA over time and identify clinical features that may be used for PsA prediction in patients with psoriasis (PsO). METHODS: The study population for PsA incidence analysis included 1128 participants enrolled in the Utah Psoriasis Initiative between 2002 and 2014. Clinical evaluation and medical record review were performed to identify new cases of PsA after enrollment. To identify PsO features associated with PsA, the population was restricted to 627 participants who did not have PsA before PsO phenotyping and had been followed up for subsequent PsA diagnosis. We conducted Cox proportional hazard regressions to estimate the HR of PsA associated with PsO characteristics and other health-related features. RESULTS: PsA incidence rate increased for > 60 years following PsO onset (trend P < 0.0001). There was a significant association between PsA and induration severity in untreated lesions (P < 0.001, HR 1.46), history of fingernail involvement (P < 0.001, HR 2.38), pustular PsO (P < 0.001, HR 3.32), fingernail involvement at enrollment (P < 0.001, HR 2.04), and Koebner phenomenon (P < 0.001, HR 1.90). Multivariate analysis yielded a model that included a history of fingernail involvement (P < 0.001, HR 2.16) and untreated induration (P < 0.001, HR 1.41). CONCLUSION: Risk of PsA increases steadily for > 60 years following PsO onset. Patient-reported history of PsO characteristics has greater predictive power than physician-measured features at enrollment visits. The characteristics identified in this study provide guidance for screening for PsA risk in patients with PsO.

Bacterial Communities in the Alpaca Gastrointestinal Tract Vary With Diet and Body Site.

Gut -associated microbes ('gut microbiota') impact the nutrition of their hosts, especially in ruminants and pseudoruminants that consume high-cellulose diets. Examples include the pseudoruminant alpaca. To better understand how body site and diet influence the alpaca microbiota, we performed three 16S rRNA gene surveys. First, we surveyed the compartment 1 (C1), duodenum, jejunum, ileum, cecum, and large intestine (LI) of alpacas fed a grass hay (GH; tall fescue) or alfalfa hay (AH) diet for 30 days. Second, we performed a C1 survey of alpacas fed a series of 2-week mixed grass hay (MGH) diets supplemented with ∼25% dry weight barley, quinoa, amaranth, or soybean meal. Third, we examined the microbial differences of alpacas with normal versus poor body condition. Samples from GH- and AH-fed alpacas grouped by diet and body site but none of the four supplements significantly altered C1 microbiota composition, relative to each other, and none of the OTUs were differentially abundant between alpacas with normal versus poor body conditions. Taken together, the findings of a diet- and body-site specific alpaca microbiota are consistent with previous findings in ruminants and other mammals, but we provide no evidence to link changes in alpaca body condition with variation in microbiota relative abundance or identity.

Draft Genome Sequence of Lactobacillus paracasei DmW181, a Bacterium Isolated from Wild Drosophila.

The draft genome sequence of Lactobacillus paracasei DmW181, an anaerobic bacterium isolate from wild Drosophila flies, is reported here. Strain DmW181 possesses genes for sialic acid and mannose metabolism. The assembled genome is 3,201,429 bp, with 3,454 predicted genes.

Genome Sequence of Leuconostoc citreum DmW_111, Isolated from Wild Drosophila.

Isolates of the lactic acid bacterium Leuconostoc citreum are a major part of fermentation processes, especially in Korean kimchi. Here, we present the genome of L. citreum DmW_111, isolated from wild Drosophila melanogaster; analysis of this genome will expand the diversity of genome sequences for non-Lactobacillus spp. isolated from D. melanogaster.

Genome Sequence of Weissella cibaria DmW_103, Isolated from Wild Drosophila.

Lactic acid bacteria are commonly associated with Drosophila spp. Here, we report on the isolation of a strain of Weissella cibaria and the sequencing, assembly, and annotation of its genome. A total of 35 contigs were generated, with 2,349 coding sequences found.

Physiological and pathological roles of the γ-secretase complex.

Gamma-secretase (GS) is an enzyme complex that cleaves numerous substrates, and it is best known for cleaving amyloid precursor protein (APP) to form amyloid-beta (Aß) peptides. Aberrant cleavage of APP can lead to Alzheimer's disease, so much research has been done to better understand GS structure and function in hopes of developing therapeutics for Alzheimer's. Therefore, most of the attention in this field has been focused on developing modulators that reduce pathogenic forms of Aß while leaving Notch and other GS substrates intact, but GS provides multiple avenues of modulation that could improve AD pathology. GS has complex regulation, through its essential subunits and other associated proteins, providing other targets for AD drugs. Therapeutics can also alter GS trafficking and thereby improve cognition, or move beyond Aß entirely, effecting Notch and neural stem cells. GS also cleaves substrates that affect synaptic morphology and function, presenting another window by which GS modulation could improve AD pathology. Taken together, GS presents a unique cross road for neural processes and an ideal target for AD therapeutics.

Cerebral vasoreactivity is impaired in treated, virally suppressed HIV-infected individuals.

OBJECTIVE: To compare cerebral vasoreactivity, a measure of cerebrovascular endothelial function, between treated, virally suppressed HIV-infected individuals and HIV-uninfected controls and to evaluate the effect of HIV-specific factors on cerebral vasoreactivity. METHODS: Cross-sectional study of 65 antiretroviral therapy-treated, virally suppressed HIV-infected individuals and 28 HIV-uninfected controls. Participants underwent noninvasive assessment of cerebral vasoreactivity using transcranial Doppler ultrasound and inhaled carbon dioxide (CO2). We used mixed effects multivariable linear regression to determine the association of HIV infection and HIV-specific factors with cerebral vasoreactivity. RESULTS: Mean age was 57.2 years for HIV-infected participants and 53.5 years for HIV-uninfected controls. Most participants (95%) were men. Twenty-six per cent of HIV-infected participants were nonwhite compared to 32% of controls. Among HIV-infected participants, mean CD4 cell count was 596 cells/µl, and mean duration of viral suppression was 7.8 years. Cerebral vasoreactivity in response to hypercapnia (cerebral VRhyper) was lower in HIV-infected individuals compared to uninfected controls (3.23 versus 3.81%, P = 0.010). After adjusting for demographic and vascular risk factors, HIV infection was independently associated with lower cerebral vasoreactivity (-0.86%, 95% CI -1.30 to -0.42%, P < 0.001). We did not find a statistically significant effect of recent or nadir CD4 cell count on cerebral vasoreactivity. There was a trend toward higher cerebral vasoreactivity for each additional year of viral suppression. CONCLUSION: Treated, virally suppressed HIV infection negatively impacted cerebral vasoreactivity even after adjustment for traditional vascular risk factors. These data highlight the potential contribution of cerebrovascular endothelial dysfunction to the elevated risk of stroke observed in HIV-infected individuals.