Man With Bilateral Leg Swelling

A 52-year-old man without known medical history presented with painful, progressive, bilateral lower extremity edema over a two-week period. An abdominal exam noted a firm left upper quadrant mass. Emergency department (ED) point-of-care ultrasound (POCUS) revealed a hyperechoic, heterogeneous structure in the inferior vena cava that was determined to represent a tumor thrombus extending from a primary renal cell carcinoma. This case demonstrates how POCUS was valuable in rapidly diagnosing this rare cause of lower extremity edema and its usefulness in directing the initial ED management of this patient

Test of a Workforce Development Intervention to Expand Opioid Use Disorder Treatment Pharmacotherapy Prescribers: Protocol for a Cluster Randomized Trial

Background: Overdoses due to non-medical use of prescription opioids and other opiates have become the leading cause of accidental deaths in the USA. Buprenorphine and extended-release naltrexone are key evidence-based pharmacotherapies available to addiction treatment providers to address opioid use disorder (OUD) and prevent overdose deaths. Treatment organizations’ efforts to provide these pharmacotherapies have, however, been stymied by limited success in recruiting providers (physicians, nurse practitioners, and physician assistants) to prescribe these medications. Historically, the addiction treatment field has not attracted physicians, and many barriers to implementing OUD pharmacotherapy exist, ranging from lack of confidence in treating OUD patients to concerns regarding reimbursement. Throughout the USA, the prevalence of OUD far exceeds the capacity of the OUD pharmacotherapy treatment system. Poor access to OUD pharmacotherapy prescribers has become a workforce development need for the addiction treatment field and a significant health issue. Methods: This cluster randomized controlled trial (RCT) is designed to increase buprenorphine and extended-release naltrexone treatment capacity for OUD. The implementation intervention to be tested is a bundle of OUD pharmacotherapy capacity building practices called the Prescriber Recruitment Bundle (PRB), which was developed and piloted in a previous statewide buprenorphine implementation study. For this cluster RCT, organizational sites will be recruited and then randomized into one of two arms: (1) control, with treatment as usual and access to a website with PRB resources, or (2) intervention, with organizations implementing the PRB using the Network for the Improvement of Addiction Treatment organizational change model over a 24-month intervention period and a 10-month sustainability period. The primary treatment outcomes for each organizational site are self-reported monthly counts of buprenorphine slots, extended-release naltrexone capacity, number of buprenorphine patients, and number of extended-release naltrexone patients. This trial will be conducted in Florida, Ohio, and Wisconsin, resulting in 35 sites in each arm, for a total sample size of 70 organizations. Discussion: This study addresses three issues of substantial public health significance: (1) the pressing opioid misuse epidemic, (2) the low uptake of OUD treatment pharmacotherapies, and (3) the need to increase prescriber participation in the addiction treatment workforce. Trial Registration: ClinicalTrials.gov NCT02926482

The Neurotensin Receptor-1 Pathway Contributes to Human Ductal Breast Cancer Progression

BACKGROUND: The neurotensin (NTS) and its specific high affinity G protein coupled receptor, the NT1 receptor (NTSR1), are considered to be a good candidate for one of the factors implicated in neoplastic progression. In breast cancer cells, functionally expressed NT1 receptor coordinates a series of transforming functions including cellular migration and invasion. METHODS AND RESULTS: we investigated the expression of NTS and NTSR1 in normal human breast tissue and in invasive ductal breast carcinomas (IDCs) by immunohistochemistry and RT-PCR. NTS is expressed and up-regulated by estrogen in normal epithelial breast cells. NTS is also found expressed in the ductal and invasive components of IDCs. The high expression of NTSR1 is associated with the SBR grade, the size of the tumor, and the number of metastatic lymph nodes. Furthermore, the NTSR1 high expression is an independent factor of prognosis associated with the death of patients. CONCLUSION: these data support the activation of neurotensinergic deleterious pathways in breast cancer progression

The hydrogen-poor superluminous supernova iPTF 13ajg and its host galaxy in absorption and emission

We present imaging and spectroscopy of a hydrogen-poor superluminous supernova (SLSN) discovered by the intermediate Palomar Transient Factory, iPTF 13ajg. At a redshift of z = 0.7403, derived from narrow absorption lines, iPTF 13ajg peaked at an absolute magnitude of M u, AB = -22.5, one of the most luminous supernovae to date. The observed bolometric peak luminosity of iPTF 13ajg is 3.2 × 1044 erg s-1, while the estimated total radiated energy is 1.3 × 1051 erg. We detect narrow absorption lines of Mg I, Mg II, and Fe II, associated with the cold interstellar medium in the host galaxy, at two different epochs with X-shooter at the Very Large Telescope. From Voigt profile fitting, we derive the column densities log N(Mg I) =11.94 ± 0.06, log N(Mg II) =14.7 ± 0.3, and log N(Fe II) =14.25 ± 0.10. These column densities, as well as the Mg I and Mg II equivalent widths of a sample of hydrogen-poor SLSNe taken from the literature, are at the low end of those derived for gamma-ray bursts (GRBs) whose progenitors are also thought to be massive stars. This suggests that the environments of hydrogen-poor SLSNe and GRBs are different. From the nondetection of Fe II fine-structure absorption lines, we derive a lower limit on the distance between the supernova and the narrow-line absorbing gas of 50 pc. The neutral gas responsible for the absorption in iPTF 13ajg exhibits a single narrow component with a low velocity width, ΔV = 76 km s-1, indicating a low-mass host galaxy. No host galaxy emission lines are detected, leading to an upper limit on the unobscured star formation rate (SFR) of SFR. Late-time imaging shows the iPTF 13ajg host galaxy to be faint, with g AB 27.0 and R AB ≥ 26.0 mag, corresponding to M B, Vega ≳ -17.7 mag. © 2014. The American Astronomical Society. All rights reserved.

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Man With Bilateral Leg Swelling

A 52-year-old man without known medical history presented with painful, progressive, bilateral lower extremity edema over a two-week period. An abdominal exam noted a firm left upper quadrant mass. Emergency department (ED) point-of-care ultrasound (POCUS) revealed a hyperechoic, heterogeneous structure in the inferior vena cava that was determined to represent a tumor thrombus extending from a primary renal cell carcinoma. This case demonstrates how POCUS was valuable in rapidly diagnosing this rare cause of lower extremity edema and its usefulness in directing the initial ED management of this patient

Use of telemedicine in addiction treatment: current practices and organizational implementation characteristics.

Telemedicine applications offer innovative approaches for treating and reducing the effects of substance use disorders (SUDs). This analysis assessed the interest in and use of 11 telemedicine applications in a sample of 363 SUD organizations in the United States of America. Fifty percent of the organizations expressed high rates of interest in seven of the telemedicine applications, demonstrating the appeal of telemedicine within this field. The top three self-reported telemedicine applications being used were (1) computerized screening/assessments (44.6%), (2) telephone-based recovery supports (29.5%), and (3) telephone-based therapy (28.37%). The greatest gaps between interest and use were for (1) texting appointment reminders (55.2% differential), (2) mobile apps for posttreatment recovery (46.6% differential), and (3) recovery support chats (46.6% differential). A Latent Class Analysis (LCA) of the organizations' telemedicine use behavior identified three groupings: "Innovators" that were using a range of technologies ( = 27, 7.4%); "Technology Traditionalists" that limited their use to telephone, video, and web portal technologies ( = 101, 27.8%); and "Low Tech" that had low overall technology use ( = 235, 64.7%). Future studies should build on how telemedicine could be applied in SUD settings, organizational behaviors towards its adoption, and telemedicine's effect on treatment adherence and clinical outcomes