LINC01432 binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy.

Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression- free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA, LINC01432 . We investigated LINC01432 overexpression and CRISPR/Cas9 knockdown in MM cell lines to show that LINC01432 overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show that LINC01432 directly interacts with the RNA binding protein, CELF2. Lastly, we showed that LINC01432 -targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterized LINC01432, which inhibits apoptosis. Key points: lncRNA expression was found to be dysregulated in patients with short PFS to standard multiple myeloma therapy. LINC01432 -bound CELF2 inhibits apoptosis.

Computed Tomography Appearance of the "Whirlpool Sign" in Ovarian Torsion.

CASE PRESENTATION: A 28-year-old female presented to the emergency department complaining of right lower abdominal pain. A contrast-enhanced computed tomography (CT) was done, which showed a 15-centimeter right adnexal cyst with adjacent "whirlpool sign" concerning for right ovarian torsion. Transvaginal pelvic ultrasound (US) revealed a hemorrhagic cyst in the right adnexa, with duplex Doppler identifying arterial and venous flow in both ovaries. Laparoscopic surgery confirmed right ovarian torsion with an attached cystic mass, and a right salpingo-oophorectomy was performed given the mass was suspicious for malignancy. DISCUSSION: Ultrasound is the test of choice for diagnosis of torsion due to its ability to evaluate anatomy and perfusion. When ovarian pathology is on the patient's right, appendicitis is high in the differential diagnosis, and CT may be obtained first. Here we describe a case where CT first accurately diagnosed ovarian torsion by demonstrating the whirlpool sign, despite an US that showed arterial flow to the ovary. Future studies should determine whether CT alone is sufficient to diagnose or exclude ovarian torsion.

Assessment of clinical dehydration using point of care ultrasound for pediatric patients in rural Panama.

BACKGROUND: Dehydration and its associated symptoms are among the most common chief complaints of children in rural Panama. Previous studies have shown that intravascular volume correlates to the ratio of the diameters of the inferior vena cava (IVC) to the aorta (Ao). Our study aims to determine if medical students can detect pediatric dehydration using ultrasound on patients in rural Panama. METHODS: This was a prospective, observational study conducted in the Bocas del Toro region of rural Panama. Children between the ages of 1 to 15 years presenting with diarrhea, vomiting, or parasitic infection were enrolled in the study. Ultrasound measurements of the diameters of the IVC and abdominal aorta were taken to assess for dehydration. RESULTS: A total of 59 patients were enrolled in this study. Twenty-four patients were clinically diagnosed with dehydration and 35 were classified to have normal hydration status. Of the 24 patients with dehydration, half (n=12) of these patients had an IVC/Ao ratio below the American threshold of 0.8. Of the remaining asymptomatic subjects, about half (n=18) of these subjects also had an IVC/Ao ratio below the American threshold of 0.8. CONCLUSION: Our study did not support previous literature showing that the IVC/Ao ratio is lower in children with dehydration. It is possible that the American standard for evaluating clinical dehydration is not compatible with the rural pediatric populations of Panama.

Feasibility study of minimally trained medical students using the Rural Obstetrical Ultrasound Triage Exam (ROUTE) in rural Panama.

BACKGROUND: Maternal and infant mortality rates reported in rural Panama are greater than those in urban regions. Bocas del Toro is a region of Panama inhabited by indigenous people at greater risk for pregnancy-related complications and deaths due to geographic isolation and limited access to health care. Portable ultrasound training programs have recently been implemented in low-resource settings to increase access to diagnostic imaging. The goal of this study is to determine the feasibility of teaching first-year medical students the Rural Obstetrical Ultrasound Triage Exam (ROUTE) to help identify pathology in pregnant women of the Bocas del Toro region of Panama. METHODS: Eight first-year medical students completed ROUTE training sessions. After training, the students were compared to professional sonographers to evaluate their accuracy in performing the ROUTE. Students then performed the ROUTE in mobile clinics within Bocas del Toro. They enrolled women pregnant in their 2nd or 3rd trimesters and measured biparietal diameter, head circumference, amniotic fluid index, fetal lie and placental position. Any abnormal measurement would be further analyzed by the lead physician for a potential hospital referral. RESULTS: A total of 60 women were enrolled in the study. Four women were detected as having a possible high-risk pregnancy and thus referred to a hospital for further evaluation. CONCLUSION: Based on our data, first-year medical students with additional training can use the ROUTE to identify complications in pregnancy using ultrasound in rural Panama. Additional studies are required to determine the optimal amount of training required for proficiency.

Brief report: Lactobacillus bulgaricus GLB44 (Proviotic™ ) plus esomeprazole for Helicobacter pylori eradication: A pilot study.

BACKGROUND: Recent studies of Lactobacillus delbrueckii subsp. bulgaricus GLB44 plus a proton-pump inhibitor (PPI) reported cures of more than 90% of patients with active Helicobacter pylori infections. AIM: To confirm the high H. pylori cure rates reported previously. METHOD: A pilot study was done in healthy H. pylori-infected volunteers using 3-gram sachet (3 billion cells) of L. delbrueckii GLB44 plus 22.3 mg of esomeprazole b.i.d., for 14 days. The result was determined by urea breath testing 4 weeks after therapy. Stopping rules required for ending enrollment if less than 3 of the first 10 subjects were cured. RESULTS: Nine subjects were entered and because all failed to achieve negative urea breath test, the stopping rule required the study to end. CONCLUSION: We were unable to confirm reports of achieving a high H. pylori cure rate with L. delbrueckii GLB44 plus a PPI.

Feasibility study of minimally trained medical students using the Rural Obstetrical Ultrasound Triage Exam (ROUTE) in rural Panama / 世界急诊医学杂志（英文）

BACKGROUND:Maternal and infant mortality rates reported in rural Panama are greater than those in urban regions. Bocas del Toro is a region of Panama inhabited by indigenous people at greater risk for pregnancy-related complications and deaths due to geographic isolation and limited access to health care. Portable ultrasound training programs have recently been implemented in low-resource settings to increase access to diagnostic imaging. The goal of this study is to determine the feasibility of teaching first-year medical students the Rural Obstetrical Ultrasound Triage Exam (ROUTE) to help identify pathology in pregnant women of the Bocas del Toro region of Panama. METHODS:Eight first-year medical students completed ROUTE training sessions. After training, the students were compared to professional sonographers to evaluate their accuracy in performing the ROUTE. Students then performed the ROUTE in mobile clinics within Bocas del Toro. They enrolled women pregnant in their 2nd or 3rd trimesters and measured biparietal diameter, head circumference, amniotic fluid index, fetal lie and placental position. Any abnormal measurement would be further analyzed by the lead physician for a potential hospital referral. RESULTS:A total of 60 women were enrolled in the study. Four women were detected as having a possible high-risk pregnancy and thus referred to a hospital for further evaluation. CONCLUSION:Based on our data, first-year medical students with additional training can use the ROUTE to identify complications in pregnancy using ultrasound in rural Panama. Additional studies are required to determine the optimal amount of training required for proficiency.