Acute Diarrhea in North American Students after Relocation to Israel: A Pilot Study.

BACKGROUND: Travelers' diarrhea (TD) is frequently encountered in people traveling from high-income to low-income countries; however, its epidemiology in those traveling between high-income countries is not known. OBJECTIVES: To evaluate the incidence of diarrhea in North American students relocating to Israel. METHODS: A retrospective cohort study involving medical students from the United States and Canada relocating to Israel was conducted. Students who relocated to Israel during 2010-2016 were contacted by email to participate in an anonymous survey. Data included demographic information as well as occurrence, timing, duration, and outcome of diarrhea after relocation. RESULTS: Ninety-seven students participated in the survey. Most (93.7%) students relocated from the United States or Canada. The period-prevalence of diarrhea was 69.1%. The incidence of diarrhea declined from 34.8 cases per 100 student-months during the first month after relocation to 1.3 cases per 100 student-months after 1 year. The duration of diarrhea was up to 1 week in 72.7%. Students who reported diarrhea were younger than students who did not (mean age 24.0 ± 2.2 and 28.4 ± 1.8 years, respectively, P < 0.001). No other demographic parameter was significantly associated with a higher likelihood of diarrhea. CONCLUSIONS: A high proportion of North American medical students relocating to Israel reported diarrhea with clinical and epidemiological features similar to classic TD. Further studies are needed to elucidate the causative agents of TD in Israel.

Obstructive Sleep Apnea as the First Presentation of Juvenile Nasal Angiofibroma.

CITATION: Lobl M, Zandieh SO. Obstructive sleep apnea as the first presentation of juvenile nasal angiofibroma. J Clin Sleep Med. 2019;15(9):1373-1375.

Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review.

UNLABELLED: The 'vanishing bone' syndrome multicentric osteolysis with nodulosis and arthropathy (MONA) is a rare chronic skeleton disorder caused by matrix metalloproteinase 2 (MMP2) deficiency, mimicking erosive polyarticular juvenile idiopathic arthritis. MONA is characterised by facial dysmorphism, subcutaneous fibrocollagenous nodules, carpal and tarsal osteolysis and interphalangeal joint erosions. We present the case of a 5-year-old boy with double outlet right ventricle, ventricular septal defect, coarctation of the aorta and MONA. Previously, a total of 24 cases of MONA have been reported of which six also had congenital cardiac malformations. Despite treatment attempts of our patient with methotrexate, eternacept and prednisolone, serial X-ray studies documented continuous severe bone degeneration. CONCLUSION: The case documents the natural history of MONA and establishes a link between MMP2 deficiency and heart development, and given the recurring cardiac association, we suggest that all MONA patients be examined for possible cardiac defects.

Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome.

The "vanishing bone" syndromes represent a group of rare skeletal disorders characterized by osteolysis and joint destruction, which can mimic severe rheumatoid arthritis. Winchester syndrome was one of the first recognized autosomal-recessive, multicentric forms of the disorder. It was originally described nearly 50 years ago in two sisters with a severe crippling osteolysis. Using cultured fibroblasts from the proband, we have now identified homozygous mutations in membrane type-1 metalloproteinase (MT1-MMP or MMP14). We demonstrate that the resulting hydrophobic-region signal-peptide substitution (p.Thr17Arg) decreases MT1-MMP membrane localization with consequent impairment of pro-MMP2 activation, and we propose a structure-based mechanism for this effect.

IGFBP-4 tumor and serum levels are increased across all stages of epithelial ovarian cancer.

BACKGROUND: We sought to identify candidate serum biomarkers for the detection and surveillance of EOC. Based on RNA-Seq transcriptome analysis of patient-derived tumors, highly expressed secreted proteins were identified using a bioinformatic approach. METHODS: RNA-Seq was used to quantify papillary serous ovarian cancer transcriptomes. Paired end sequencing of 22 flash frozen tumors was performed. Sequence alignments were processed with the program ELAND, expression levels with ERANGE and then bioinformatically screened for secreted protein signatures. Serum samples from women with benign and malignant pelvic masses and serial samples from women during chemotherapy regimens were measured for IGFBP-4 by ELISA. Student's t Test, ANOVA, and ROC curves were used for statistical analysis. RESULTS: Insulin-like growth factor binding protein (IGFBP-4) was consistently present in the top 7.5% of all expressed genes in all tumor samples. We then screened serum samples to determine if increased tumor expression correlated with serum expression. In an initial discovery set of 21 samples, IGFBP-4 levels were found to be elevated in patients, including those with early stage disease and normal CA125 levels. In a larger and independent validation set (82 controls, 78 cases), IGFBP-4 levels were significantly increased (p < 5 × 10-5). IGFBP-4 levels were ~3× greater in women with malignant pelvic masses compared to women with benign masses. ROC sensitivity was 73% at 93% specificity (AUC 0.816). In women receiving chemotherapy, average IGFBP-4 levels were below the ROC-determined threshold and lower in NED patients compared to AWD patients. CONCLUSIONS: This study, the first to our knowledge to use RNA-Seq for biomarker discovery, identified IGFBP-4 as overexpressed in ovarian cancer patients. Beyond this, these studies identified two additional intriguing findings. First, IGFBP-4 can be elevated in early stage disease without elevated CA125. Second, IGFBP-4 levels are significantly elevated with malignant versus benign disease. These findings provide the rationale for future validation studies.