Citations

Background Patient-reported signs and symptoms are often the first indication of clinically relevant lymphedema. Objective The purpose of this study was to develop and assess the diagnostic accuracy of a screening questionnaire to detect lower-extremity lymphedema (LEL) among normal-weight women and women with obesity. Design This was a cross-sectional survey study. Methods The authors reviewed existing questionnaires assessing upper-extremity lymphedema (UEL) for potential questions and worked with content experts to generate new items. A draft questionnaire with 59 items was reviewed by 5 physicians and 5 physical therapists who specialized in lymphedema management and 5 female patients with clinically confirmed secondary LEL. A revised questionnaire with 45 items was administered by mail to 186 women with clinically confirmed LEL (n=116) or UEL (n=70). A total of 99 women (53.2% of 186) completed the mailed survey, and 28 women with lymphedema who were recruited directly in a lymphedema clinic waiting area also completed the survey. A parsimonious subset of items that best discriminated patients with and without LEL was identified using chi-square tests and logistic regression. Sensitivity and specificity for detecting LEL and positive and negative likelihood ratios (LR+, LR−) were estimated for the entire sample and for subsamples defined by obesity (body mass index ≥30 versus <30 kg/m2), which may confound the accurate diagnosis of LEL. Results Questionnaires were completed by 127 women (LEL group, n=88; UEL group, n=39). A sum of 13 items (score range=0–52) was the most discriminating. Using a cutoff score of ≥5 points, the sensitivity and specificity for detecting LEL among all participants were 95.5% and 86.5%, respectively (LR+=7.1, LR−=0.05), and 94.8% and 76.5%, respectively (LR+=4.0, LR−=0.07), for participants who were obese. Limitations By enumerating a sample with a high prevalence of LEL, a spectrum bias may have been introduced, which may have affected the accuracy of the screening questionnaire. Conclusions The brief, 13-item self-report questionnaire is a sensitive and specific tool for detecting clinically relevant LEL among women, including those with a body mass index of ≥30 kg/m2.

Rationale: Mutagenesis screening is a powerful genetic tool for probing biological mechanisms underlying vertebrate development and human diseases. However, the increased colony management efforts in vertebrates impose a significant challenge for identifying genes affecting a particular organ, such as the heart, especially those exhibiting adult phenotypes on depletion. Objective: We aim to develop a facile approach that streamlines colony management efforts via enriching cardiac mutants, which enables us to screen for adult phenotypes. Methods and Results: The transparency of the zebrafish embryos enabled us to score 67 stable transgenic lines generated from an insertional mutagenesis screen using a transposon-based protein trapping vector. Fifteen lines with cardiac monomeric red fluorescent protein reporter expression were identified. We defined the molecular nature for 10 lines and bred them to homozygosity, which led to the identification of 1 embryonic lethal, 1 larval lethal, and 1 adult recessive mutant exhibiting cardiac hypertrophy at 1 year of age. Further characterization of these mutants uncovered an essential function of methionine adenosyltransferase II, α a (mat2aa) in cardiogenesis, an essential function of mitochondrial ribosomal protein S18B (mrps18b) in cardiac mitochondrial homeostasis, as well as a function of DnaJ (Hsp40) homolog, subfamily B, member 6b (dnajb6b) in adult cardiac hypertrophy. Conclusions: We demonstrate that transposon-based gene trapping is an efficient approach for identifying both embryonic and adult recessive mutants with cardiac expression. The generation of a zebrafish insertional cardiac mutant collection shall facilitate the annotation of a vertebrate cardiac genome, as well as enable heart-based adult screens.

ABSTRACTA 57-year-old woman with common variable immune deficiency and liver failure of unknown etiology presented with recurrent fevers over a 5-month period. She was found to haveHelicobacter canisbacteremia. Immunocompromised hosts with exposure to cats or dogs may be at risk for infection with this organism, which may be challenging to diagnose.

ABSTRACT Vesicular stomatitis virus (VSV) is potent and a highly promising agent for the treatment of cancer. However, translation of VSV oncolytic virotherapy into the clinic is being hindered by its inherent neurotoxicity. It has been demonstrated that selected picornaviral internal ribosome entry site (IRES) elements possess restricted activity in neuronal tissues. We therefore sought to determine whether the picornavirus IRES could be engineered into VSV to attenuate its neuropathogenicity. We have used IRES elements from human rhinovirus type 2 (HRV2) and foot-and-mouth disease virus (FMDV) to control the translation of the matrix gene (M), which plays a major role in VSV virulence. In vitro studies revealed slowed growth kinetics of IRES-controlled VSVs in most of the cell lines tested. However, in vivo studies explicitly demonstrated that IRES elements of HRV2 and FMDV severely attenuated the neurovirulence of VSV without perturbing its oncolytic potency.

Pazopanib and paclitaxel produce cytotoxic synergy in thyroid cancer models through inhibition of aurora kinase A.