Notes

[Multiple myeloma in the pathologist's perspective].
The release of late spermatids from the seminiferous epithelium requires the internalization of intercellular junctions by Sertoli cell specific structures called 'tubulobulbar complexes' (TBCs). These large, endocytic devices likely evolved from classic clathrin-mediated endocytosis machinery (CME), but have several important morphological differences to CME vesicles. Most notable among these differences is that extensive endoplasmic reticulum (ER) membrane contact sites (MCSs) occur with TBCs and not with clathrin coated pits. One of the well-established functions of ER MCSs is lipid exchange. Previously, we have established that the ORP9 lipid exchange protein is localized to the TBC-ER MCS; however, the function of ORP9 and lipid exchange at the sites is not known. Here we use an in vivo knockdown approach to probe function. #link# The testes of Sprague-Dawley rats were injected with ORP9 targeted siRNA or non-targeted reagents, and the tissues examined by bright field, super-resolution (STED), and electron microscopy. Knockdown of ORP9 was achieved and maintained with daily injections of siRNA for 2-3 day intervals. Compared to controls, sections from ORP9 siRNA injected testes had longer TBC tubes and fewer fused TBC bulbs. Late spermatids were also abnormally retained in the epithelium of knockdown tissue. These results suggest that ORP9 is necessary for normal TBC bulb vesiculation and fusion, most likely by changing the plasma membrane lipid profile of the TBC. These data also further support the conclusion that TBCs are part of the normal mechanism of sperm release.
simulation based teaching is a powerful tool in medical education, allowing hands on practice under a controlled environment and with repeated maneuvers. Central venous access venipuncture is one of the most frequent procedures carried out in the hospital setting, due to its various clinical indications and, when performed with the help of ultrasonography, the risk of adverse events is minimized. Aim to develop, to describe and to test Enpp1IN1 that simulates the central venous access puncture aided by ultrasonography.

a low cost porcine model was developed to train medical students and residents on central venous access guided by ultrasonography. Both students and medical residents underwent a theoretical training regarding the model, followed by a hands-on training session. link2 Afterwards, the participants assessed the model by answering a questionnaire.

there were 51 participants. The average score regarding the similarity between the model and the human anatomy was 9.15. When the characteristics were separately assessed, the mean scores regarding the similarity of the vessels, anatomic disposition and ultrasonographic characteristics as well as the venipuncture were, respectively, 9.27; 9.31; 9.54 and 8.86.

The model was approved and considered appropriate for the training of central venous venipuncture by all the participants. Furthermore, it is a low cost, simple and reproducible model, that presents high similarity with the human anatomy. Therefore, it may be used as an aid to train people on ultrasonography guided central venous access.
The model was approved and considered appropriate for the training of central venous venipuncture by all the participants. Furthermore, it is a low cost, simple and reproducible model, that presents high similarity with the human anatomy. Therefore, it may be used as an aid to train people on ultrasonography guided central venous access.Investigations leading to a WHO-validated declaration of elimination of schistosomiasis transmission are contemplated for several countries, including Caribbean island nations. With assistance from the Pan American Health Organization, we undertook freshwater snail surveys in two such nations, Antigua and Barbuda, and Montserrat in September and October 2017. Historically, the transmission of Schistosoma mansoni supported by the Neotropical vector snail Biomphalaria glabrata occurred in both countries. Transmission on the islands is thought to have been interrupted by the treatment of infected people, improved sanitation, introduction of competitor snails, and on Montserrat with the eruption of the Soufrière volcano which decimated known B. glabrata habitats. Guided by the available literature and local expertise, we found Biomphalaria snails in seven of 15 and one of 14 localities on Antigua and Montserrat, respectively, most of which were identified anatomically and molecularly as Biomphalaria kuhniana. Two localities on Antigua harbored B. link3 glabrata, but no schistosome infections in snails were found. For snail-related aspects of validation of elimination, there are needs to undertake basic local training in medical malacology, be guided by historical literature and recent human schistosomiasis surveys, improve and validate sampling protocols for aquatic habitats, enlist local expertise to efficiently find potential transmission sites, use both anatomical and molecular identifications of schistosomes or putative vector snail species found, if possible determine the susceptibility of recovered Biomphalaria spp. to S. mansoni, publish survey results, and provide museum vouchers of collected snails and parasites as part of the historical record.Phytochemical investigation of the leaves of Lepisanthes rubiginosa led to the isolation of two new glycosides, lepisantheside A (1) and lepisantheside B (2), together with two known compounds acutoside A (3) and 3-O-[β-D-xylopyranosyl-(1→3)-β-D-glucopyranosyl-]-oleanolic acid (4). Their structures were elucidated by means of spectroscopic methods (HR-ESI-MS, 1D and 2D NMR), and by comparison with the reported data. The cytotoxicity of compounds 1-4 against four human cancer cell lines (KB, HepG2, SK-LU-1 and MCF7) was evaluated. Compound 4 exhibited significant activity with IC50 values of 9.57, 6.66, 6.97 and 18.32 µM, respectively, in comparison with the postive control ellipticine.We investigate the immediate social context of contraceptive behaviors specifically, the intimate relationship. We use the Relationship Dynamics and Social Life (RDSL) study (2008-2012), based on a random sample of 1,003 women ages 18-19 residing in a Michigan county. Women were interviewed weekly for 2.5 years, resulting in an age range of 18-22. We test three sets of hypotheses about change over time within a relationship, using relationship-level within-between models, which compare a couple's contraceptive behaviors across different times in the relationship. First, we find that a couple is less likely to use contraception when the relationship is more intimate and/or committed and that a couple becomes less likely to use contraception over time, regardless of intimacy and commitment. Second, we find that a couple using contraception becomes increasingly likely to choose hormonal over coital methods, but this change occurs as a relationship endures and is unrelated to intimacy and/or commitment. Third, we find that a condom-using couple's consistency does not decline when there is conflict; rather, consistency of condom use declines over time regardless of the relationship's characteristics. We also demonstrate that conflict and power imbalance increase reliance on hormonal methods among those using contraception; conflict decreases consistency among withdrawal (but not condom) users; and nonmonogamy increases reliance on condoms and decreases withdrawal consistency. The strong and consistent link between duration and contraceptive behaviors-regardless of intimacy, commitment, conflict, or power imbalance-suggests that the continual vigilance required for long-term contraceptive use is difficult during early emerging adulthood.This report is dedicated to determination of anticancer drug methotrexate (MTX) in human urine using surface-enhanced Raman spectroscopy (SERS). Aluminum oxide loaded with silver nanoparticles (AO-Ag) was proposed as SERS-active sorbent and used for solid-phase extraction (SPE) of the analyte and its SERS-based determination (SPE-SERS protocol). MTX has strong SERS signal only in alkaline media that challenges its determination in urine due to strong background signal caused by creatinine. The application of SPE step enables to purify and concentrate the analyte making MTX determination possible. Also, the application of the same material for SPE pretreatment and SERS analysis enables to simplify and speed-up the protocol. The protocol was developed and tested using artificially spiked samples of human urine collected during different time of day to account deviating composition of the urine matrix. The use of dilution step of the analyte-containing urine was proposed prior SPE-SERS protocol to reduce the difference between morning-time- and daytime-collected urine achieving maximal reliability of the analysis. Additional physicochemical study was performed to estimate an influence of the primary intrinsic urine components (salts, urea, creatinine) and their mixtures on the analytical signal. Final protocol enables MTX determination in human urine within 20-300 μg mL-1 range of concentrations with satisfactory precision (11-19% RSD), accuracy (97-104% apparent recovery), and limit of detection (4.2 μg mL-1). Accounting that the analysis requires less than 15 min and portable Raman spectrometer, the protocol seems to be promising for therapeutic drug monitoring in hospitals to identify poor MTX clearance in a timely manner and minimize adverse effects of therapy. Graphical Abstract.The current public health crisis has exposed deep cracks in social equality and justice for marginalised and vulnerable communities around the world. The reported rise in the number of 'do not resuscitate' orders being imposed on people with disabilities has caused particular concerns from a human rights perspective. While the evidence of this is contested, this article will consider the human rights implications at stake and the dangers associated with using 'quality of life' measures as determinant of care in medical decision-making and triage assessments.EBV-associated gastric adenocarcinomas (EBVaGCs) often exhibit better clinical outcomes than EBV negative gastric cancers (GCs), which could be related to their consistent expression of foreign viral antigens. Antigen-presenting cells (APCs) present peptide antigens in the context of the class-II major histocompatibility complex (MHC-II). During inflammatory conditions, epithelial cells express MHC-II and function as accessory APCs. Utilizing RNA-seq data from nearly 400 GC patients, we determined the impact of EBV-status on expression of MHC-II components, genes involved in their regulation, and T-cell co-stimulation. Virtually all MHC-II genes were significantly upregulated in EBVaGCs compared to normal tissues, or other GC subtypes. Genes involved in antigen presentation were also significantly upregulated in EBVaGCs, as were the key MHC-II transcriptional regulators CIITA and RFX5. This was unexpected as the EBV encoded BZLF1 protein can repress CIITA transcription and is expressed in many EBVaGCs. Furthermore, MHC-II upregulation was strongly correlated with elevated intratumoral levels of interferon-gamma. In addition, expression of co-stimulatory molecules involved in T-cell activation and survival was also significantly increased in EBVaGCs. Thus, gastric adenocarcinoma cells may functionally contribute to the highly immunogenic tumor microenvironment observed in EBVaGCs via a previously unappreciated role in interferon-induced antigen presentation.
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