Coexpression with the inward rectifier K(+) channel Kir6.1 increases the affinity of the vascular sulfonylurea receptor SUR2B for glibenclamide.
ATP-sensitive K(+) channels are closed by the hypoglycemic sulfonylureas like glibenclamide (GBC) and activated by a class of vasorelaxant compounds, the K(+) channel openers. These channels are octamers of Kir6.x and sulfonylurea receptor (SUR) subunits with 4:4 stoichiometry. The properties of the opener-sensitive K(+) channel in the vasculature are well matched by the SUR2B/Kir6.1 channel; however, the GBC sensitivity of the recombinant channel is unknown. In binding experiments we have determined the affinity of GBC for SUR2B and the SUR2B/Kir6.1 channel and compared the results with the channel blocking potency of GBC. All experiments were performed in whole transfected human embryonic kidney cells at 37 degrees C. The equilibrium dissociation constants (K(D)) of GBC binding to SUR2B and to the SUR2B/Kir6.1 complex were determined to be 32 and 6 nM, respectively; the K(D) value of the opener P1075 (N-cyano-N'-(1, 1-dimethylpropyl)-N"-3-pyridylguanidine) ( approximately 5 nM) was, however, not affected by cotransfection. In whole cell voltage-clamp experiments, GBC inhibited the SUR2B/Kir6.1 channel with IC(50) approximately 43 nM. The data show that, in the intact cell: 1) SUR2B, previously considered to be a low-affinity SUR, has a rather high affinity for GBC; 2) coexpression with the inward rectifier Kir6.1 increases the affinity of SUR2B for GBC; 3) the recombinant channel exhibits the same GBC affinity as the opener-sensitive K(+) channel in vascular tissue; and 4) the K(D) value of GBC binding to the octameric channel is 7 times lower than the IC(50) value for channel inhibition. The latter finding suggests that occupation of all four GBC sites per channel is required for channel closure.


Hibernation-like state induced by an opioid peptide protects against experimental stroke.
Delta opioid peptide [D-ala2,D-leU5]enkephalin (DADLE) induces hibernation in summer ground squirrels, and enhances preservation and survival of isolated or transplanted lungs and hearts. In the present study, we investigated the protective effect of DADLE in the central nervous system. Adult Sprague-Dawley rats were pretreated with DADLE (4 mg/kg every 2 h x 4 injections, i.p.) or saline prior to unilateral occlusion of the middle cerebral artery (MCA). Daily behavioral tests revealed that ischemic animals treated with DADLE did not show any significant behavioral dysfunctions compared with saline-treated ischemic animals. Opioid antagonists only transiently inhibited the protective effect of DADLE, indicating the participation of non-opioid mechanisms in DADLE neuroprotection. Histological examination using triphenyltetrazolium chloride (TTC) revealed that brains from ischemic animals treated with DADLE, either alone or with adjuvant opioid blockers, exhibited almost completely intact striata. In contrast, brains from ischemic animals that received saline showed significant infarction in the lateral striatum. Analyses of apoptotic cell death revealed a significant increase in the p-53 mRNA expression in the striatum of ischemic animals that received saline, while those that received DADLE exhibited near normal striatal p-53 expression. This protective effect was accompanied by significant increments in protein levels of glial cell line-derived neurotrophic factor in the striatum of DADLE-treated ischemic animals. These results indicate that DADLE protected against necrotic and apoptotic cell death processes associated with ischemia-reperfusion injury. The present study demonstrates that delta opioids are crucially involved in stroke, suggesting that the opioid system is important in the study of brain injury and protection.


Gut microbiome in chronic rheumatic and inflammatory bowel diseases: Similarities and differences.
Inflammatory bowel diseases (IBDs) and chronic rheumatic diseases (CRDs) are systemic chronic disorders sharing common genetic, immune and environmental factors. About half of patients with IBD develop rheumatic ailments and microscopic intestinal inflammation is present in up to half of CRD patients. IBD and CRD patients also share a common therapeutic armamentarium. Disequilibrium in the complex realm of microbes (known as dysbiosis) that closely interact with the gut mucosal immune system has been associated with both IBD and CRD (spondyloarthritis and rheumatoid arthritis). Whether dysbiosis represents an epiphenomenon or a prodromal feature remains to be determined. In an attempt to further investigate whether specific gut dysbiosis may be the missing link between IBD and CRD in patients developing both diseases, we performed here a systematic literature review focusing on studies looking at bacterial microbiota in CRD and/or IBD patients. We included 80 studies, with a total of 3799 IBD patients without arthritis, 1084 CRD patients without IBD, 132 IBD patients with arthropathy manifestations and 12 spondyloarthritis patients with IBD history. Overall, this systematic review indicates that an increase in Bifidobacterium, Staphylococcus, Enterococcus, Lactobacillus, Pseudomonas, Klebsiella and Proteus genera, as well as a decrease in Faecalibacterium, Roseburia genera and species belonging to Verrucomicrobia and Fusobacteria phyla are common features in IBD and CRD patients, whereas dozens of bacterial species are specific features of CRD and IBD. Further work is needed to understand the functions of bacteria and of their metabolites but also to characterize fungi and viruses that are commonly found in these patients.


Predicting erectile function recovery after bilateral nerve sparing radical prostatectomy: a proposal of a novel preoperative risk stratification.
No multivariable model is currently available for the prediction of erectile function (EF) recovery after bilateral nerve sparing radical prostatectomy (BNSRP). The aim of this study was to develop a novel preoperative risk stratification aimed at assessing the probability of EF recovery after BNSRP. The International Index of Erectile Function (IIEF) was used to evaluate EF after BNSRP. This study included 435 patients treated with retropubic BNSRP between 2004 and 2008 at a single Institution. Preoperative data, including age, IIEF, Charlson comorbidity index (CCI), and body mass index (BMI) were available for all patients. Moreover, all patients were assessed postoperatively every 3 months and were asked to complete the IIEF during each visit. Cox regression models tested the association between preoperative predictors (age at surgery, preoperative IIEF-EF domain score, CCI, BMI) and EF recovery. Independent predictors of EF recovery were then used to stratify patients into three groups according to the risk of erectile dysfunction (ED) after surgery: low (age <or= 65 years, IIEF-EF >or= 26, CCI <or= 1; n = 184), intermediate (age 66-69 years or IIEF-EF 11-25,CCI <or= 1; n = 115), and high (age >or= 70 years or IIEF-EF <or= 10 or CCI >or= 2; n = 136). Kaplan-Meier curves assessed the time to EF recovery (defined as IIEF-EF score >or= 22). Predictive accuracy of our proposed classification was quantified using the AUC method. Of 435 patients, 242 (55.6%) received phosphodiesterase type 5 inhibitors (PDE5-I) either on demand or every day for a period of 3-6 months. Overall, EF recovery rate was 58% at 3-year follow-up. Patients treated with PDE5-I had significantly higher 3-year EF recovery rate as compared with patients left untreated after surgery (73 vs. 37%; P < 0.001). Except for BMI (P = 0.7), all preoperative covariates showed a significant association with EF recovery (all P <or= 0.04). The 3-year EF recovery rate significantly differed between the three groups, being 85, 59, and 37% in patients with low, intermediate, and high risk of postoperative ED, respectively (P < 0.001). Multivariable Cox regression analysis confirmed a highly significant association between the risk classification and EF recovery (P < 0.001). The proposed patient stratification tool showed a 69.1% accuracy. Similar results were achieved when patients were stratified according to the use of ED treatment after surgery (all P < 0.001). We report the first preoperative risk stratification tool aimed at assessing the probability of EF recovery after BNSRP. It is based on routinely available baseline data such as patient age, preoperative erectile function, and comorbidity profile.


Beyond acute appendicitis: imaging and pathologic spectrum of appendiceal pathology.
While acute appendicitis is a common and important clinical problem, a variety of other disease processes can affect the appendix. Simple and perforated appendicitis, tip appendicitis, and stump appendicitis share a common clinical presentation including anorexia, right lower quadrant pain, and fever. By imaging, most cases of acute appendicitis exhibit luminal dilation, wall thickening, and periappendiceal inflammatory stranding. In tip appendicitis, these changes are isolated to the distal appendix, often with an obstructing appendicolith. Perforated appendicitis can exhibit mural discontinuity, periappendiceal abscess, and/or extraluminal appendicoliths. After appendectomy, the appendiceal remnant or "stump" can become inflamed, often necessitating repeat surgery. Inflammatory bowel disease can involve the terminal ileum, secondarily involving the appendix, or may primarily involve the appendix. Patient symptoms can be chronic in such cases, and mucosal hyperenhancement is a pronounced imaging feature. In asymptomatic patients without appendiceal inflammation, the appendix can be dilated by intraluminal material such as inspissated succus in cystic fibrosis or mucus from benign appendiceal mucocele. Finally, neoplasms such as typical appendiceal carcinoid tumor and mucinous adenocarcinoma can involve the appendix. Carcinoids are often small and incidentally discovered at pathologic examination, while malignant mucinous adenocarcinoma tends to present with advanced disease including pseudomyxoma peritonei. Cecal cancers can also obstruct the appendiceal lumen and cause acute appendicitis; an astute radiologist can recognize this prospectively and facilitate definitive resection (right hemicolectomy) at the time of surgery. Attention to mural features, cecal configuration, and periappendiceal inflammation is essential to the correct prospective diagnosis of complicated appendicitis and less common appendiceal pathologies.


How caregivers view patient comfort and what they do to improve it: a French survey.
Intensive care unit (ICU) patients are exposed to many sources of discomfort. Most of these are related to the patient's condition, but ICU design or how care is organized also can contribute. The present survey was designed to describe the opinions of ICU caregivers on sources of patient discomfort and to determine how they were dealt with in practice. The architectural and organizational characteristics of ICUs also were analyzed in relation to patient comfort. An online, closed-ended questionnaire was developed. ICU caregivers registered at the French society of intensive care were invited to complete this questionnaire. A total of 915 staff members (55% nurses) from 264 adult and 28 pediatric ICUs completed the questionnaire. Analysis of the answers reveals that: 68% of ICUs had only single-occupancy rooms, and 66% had natural light in each room; ICU patients had access to television in 59% of ICUs; a clock was present in each room in 68% of ICUs. Visiting times were <4 h in 49% of adult ICUs, whereas 64% of respondents considered a 24-h policy to be very useful or essential to patients' well-being. A nurse-driven analgesia protocol was available in 42% of units. For caregivers, the main sources of patient discomfort were anxiety, feelings of restraint, noise, and sleep disturbances. Paramedics generally considered discomfort related to thirst, lack of privacy, and the lack of space and time references, whereas almost 50% of doctors ignored these sources of discomfort. Half of caregivers indicated they assessed sleep quality. A minority of caregivers declared regular use of noise-reduction strategies. Twenty percent of respondents admitted to having non-work-related conversations during patient care, and only 40% indicated that care often was or always was provided without closing doors. Family participation in care was planned in very few adult ICUs. Results of this survey showed that ICUs are poorly equipped to ensure patient privacy and rest. Access by loved ones and their participation in care also is limited. The data also highlighted that some sources of discomfort are less often taken into account by caregivers, despite being considered to contribute significantly.


Augmentation of the columella-labial angle to prevent the "smiling deformity" in rhinoplasty.
Aesthetic diagnosis of the smiling deformity, which is functional rather than anatomical, is essential to provide the best treatment in rhinoplasty. The nasal tip tends to rotate inferiorly during smiling, and the central upper lip moves superiorly. A posteriorly sloping upper lip with a retrodisplaced columella-labial junction gives an unaesthetic appearance. Downward movement of the tip and a sharper nasolabial angle are usually aesthetically unpleasant. In 28 nasal surgeries, augmentation of the columella-labial angle with cartilage strip grafts has been performed. The augmentation of the angle and additionally cutting of the depressor septi muscle created a wider nasolabial complex, and this angle looks full and more pleasant. This procedure has mainly been used as an additional procedure to standard reduction rhinoplasty in order to improve smiling deformity. Strip cartilage grafts were inserted subcutaneously into the upper lip extending half way to the columella and secured with a transcutaneous suture under the columella-labial angle to prevent misslocation. Augmentation by the cartilage graft together with cutting the depressor septi muscle prevented elevation and shortening of the upper lip, and also drooping of the nasal tip. This procedure provided an aesthetically pleasant appearance both at rest and during smiling.


Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations.
Allosteric modulators are called promising candidates in G protein-coupled receptor (GPCR) drug development by displaying subtype selectivity and more specific receptor modulation. Among the allosteric sites known to date, cavities at the receptor-lipid interface represent an uncharacteristic binding location that raises many questions about the ligand interactions and stability, the binding site structure, and how all of these are affected by lipid molecules. In this work, we analyze interactions in the allosteric sites of the PAR2, C5aR1, and GCGR receptors in three lipid compositions using molecular dynamics simulations. In addition, we performed quantum chemical calculations involving the symmetry-adapted perturbation theory (SAPT) and the natural population analysis to quantify the strength of intermolecular interactions. We show that besides classical hydrogen bonds, weak polar interactions such as O-HC, O-Br, and long-range electrostatics with the backbone amides contribute to the stability of allosteric modulators at the receptor-lipid interface. The allosteric cavities are detectable in various membrane compositions. The availability of polar atoms for interactions in such cavities can be assessed by water molecules from simulations. Although ligand-lipid interactions are weak, lipid tails play a role in ligand binding pose stability and the size of allosteric cavities. We discuss physicochemical aspects of ligand binding at the receptor-lipid interface and suggest a compound library enriched by weak donor groups for ligand search in such sites.


The incorporation of patient safety into board certification examinations.
In response to growing recognition of the importance of patient safety in the practice of medicine, the American Board of Medical Specialties (ABMS) is encouraging its individual specialty member boards to introduce material on patient safety into certification examinations. Certification and recertification candidates, medical schools, and residency programs will likely need to prepare for the possibility that upcoming examinations will include patient safety. Due to the relative youth of the patient safety movement, some may ask whether the field is sufficiently developed and, if so, ask what would be fair to ask candidates to know. To determine what subject matter could be reliably tested, the ABMS and the Council of Medical Specialty Societies convened a panel of patient safety experts in 2003. Based on the panel's recommendations, the authors provide a brief summary of the panel's findings and an overview of current concepts in patient safety. The authors also explore which current concepts of patient safety candidates may reasonably expect to find on upcoming examinations.


The Evolving View of Coronary Artery Calcium: A Personalized Shared Decision-Making Tool in Primary Prevention.
The 2018 American Heart Association and American College of Cardiology (AHA/ACC) cholesterol management guideline considers current evidence on coronary artery calcium (CAC) testing while incorporating learnings from previous guidelines. More than any previous guideline update, this set encourages CAC testing to facilitate shared decision making and to individualize treatment plans. An important novelty is further separation of risk groups. Specifically, the current prevention guideline recommends CAC testing for primary atherosclerotic cardiovascular disease (ASCVD) prevention among asymptomatic patients in borderline and intermediate risk groups (5-7.5% and 7.5-20% 10-year ASCVD risk). This additional sub-classification reflects the uncertainty of treatment strategies for patients broadly considered to be "intermediate risk," as treatment recommendations for high and low risk groups are well established. The 2018 guidelines, for the first time, clearly recognize the significance of a CAC score of zero, where intensive statin therapy is likely not beneficial and not routinely recommended in selected patients. Lifestyle modification should be the focus in patients with CAC = 0. In this article, we review the recent AHA/ACC cholesterol management guideline and contextualize the transition of CAC testing to a guideline-endorsed decision aid for borderline-to-intermediate risk patients who seek more definitive risk assessment as part of a clinician-patient discussion. CAC testing can reduce low-value treatment and focus primary prevention therapy on those most likely to benefit.


Current knowledge about skin-to-skin (kangaroo) care for preterm infants.
Skin-to-skin ("kangaroo") care for preterm infants is becoming widespread in Western Europe. During this care the mother holds her diaper-clad premature infant against her skin beneath her clothing and allows self-regulatory access to breast-feeding. Fathers hold their infants skin-to-skin also. Research projects in Western Europe and the United States provide data that support the safety and effectiveness of this method. Infants held skin-to-skin are warm enough and have regular heart rate and respirations, more deep sleep and alert inactivity, less crying, no increase in infections, greater weight gain, and earlier discharge. Lactation is more productive and of greater duration. Parents become attached to their infants and feel confident about caring for them. This research is summarized and annotated in a table, along with descriptive reports and videotapes. These data can be used by health care professionals to make informed decisions about offering kangaroo care opportunities to selected parents and their preterm infants.


Fungal infections complicating tumor necrosis factor alpha blockade therapy.
Tumor necrosis factor a (TNF-alpha) blockade has emerged as a useful therapy for collagen vascular diseases or graft-vs-host disease. Fungal infections complicating such therapy have been reported sporadically. MEDLINE and PubMed databases (from January 1, 1966, to June 1, 2007) were searched for reports of invasive fungal infections (IFIs) associated with the 3 available anti-TNF- alpha agents, ie, infliximab, etanercept, and adalimumab. Of the 281 cases of IFI associated with TNF-alpha inhibition, 226 (80%) were associated with infliximab, 44 (16%) with etanercept, and 11 (4%) with adalimumab. Fungal infections associated with infliximab occurred a median of 55 days (interquartile range [IQR], 15-140 days) after initiation of therapy and 3 infusions of the medication (IQR, 2-5), whereas those associated with etanercept occurred a median of 144 days (IQR, 46-240 days) after initiation of therapy. The median age of patients was 58 years (IQR, 44-68 years), and 62% were male. Use of at least 1 other immunosuppressant medication, typically a systemic corticosteroid, was reported during the course of the fungal infection in 102 (98%) of the 104 patients for whom data were available. The most prevalent IFIs were histoplasmosis (n=84 [30%]), candidiasis (n=64 [23%]), and aspergillosis (n equals 64 [23%]). Pneumonia was the most common pattern of infection. Of the 90 (32%) of 281 cases for which outcome information was available, 29 fatalities (32%) were recorded. Tumor necrosis factor a blockade is associated with IFI across a range of host groups. A high index of suspicion in patients treated with TNF-alpha antagonists is recommended because the course of such infections can be serious or fulminant, and rapid access to health care should be provided. Surveillance of IFIs complicating TNF-alpha blockade and other biologic therapies is warranted through well-organized prospective patient registries.


Music and the PACU environment.
Pain is a common problem in the PACU, resulting in negative respiratory, cardiovascular, gastrointestinal, renal, neuroendocrine, and autonomic nervous system consequences for patients. Pain relief contributes to improved patient outcomes and is also an important component of patient satisfaction, particularly in light of today's environment of high competition among hospitals for patients. Music and quiet conversation by staff, contributing to low noise levels in the PACU environment, have the potential to provide pain relief and improve patient satisfaction with the PACU experience. This study investigated the effect of soothing music and lowering noise levels on the pain experience of patients during their PACU stay. A quasiexperimental study was conducted with 2 groups of patients, one who listened to music on a day when staff kept extraneous noise at a minimum in the PACU (the experimental group) and one who experienced the typical PACU day (the control group). The study was conducted at a large Veterans Administration hospital in the Midwest. The sample consisted of 97 individuals undergoing same-day surgery from all surgery services except open heart. Pain was measured by using the 11-point Numerical Rating Scale (NRS). The experimental group experienced a significant reduction in pain from admission to the PACU until discharge. There was no significant decrease for the control group. Approximately 65% of both groups reported no pain on admission to PACU. The percentage of those in the experimental group with no pain increased to 74% at time of discharge. The percentage of those in the control group who reported no pain on discharge had decreased to 58%. A total of 99% of the participants remembered their PACU stay. When asked to remember aspects of comfort during the PACU stay, the experimental group reported (1) significantly less noise caused by staff voices and equipment, (2) greater perception of availability of nurses, and (3) significantly more positive perception of their PACU stay. The study findings support the potential for music played throughout the PACU stay to positively affect the pain experience and improve comfort among patients having surgery.


Isolation and characterization of a novel population of progenitor cells from unmanipulated rat liver.
Widespread use of liver transplantation in the treatment of hepatic diseases is restricted by the limited availability of donated organs. One potential solution to this problem would be isolation and propagation of liver progenitor cells or stem cells. Here, we report on the isolation of a novel progenitor cell population from unmanipulated (that is, no prior exposure to chemicals and no injury) adult rat liver. Rat liver cells were cultured following a protocol developed in our laboratory to generate a unique progenitor cell population called liver-derived progenitor cells (LDPCs). LDPCs were analyzed by fluorescence-activated cell sorting, real-time polymerase chain reaction (RT-PCR), immunostaining and microarray gene expression. LDPCs were also differentiated into hepatocytes and biliary epithelium in vitro and examined for mature hepatic markers and urea and albumin production. These analyses showed that, LDPCs expressed stem cell markers such as cluster domain (CD)45, CD34, c-kit, and Thy 1, similar to hematopoietic stem cells, as well as endodermal/hepatic markers such as hepatocyte nuclear factor (HNF)3beta, hematopoietically-expressed homeobox gene-1, c-met, and transthyretin. LDPCs were negative for OV-6, cytokeratins (CKs), albumin, and HNF1alpha. The microarray gene expression profile demonstrated that they showed some similarities to known liver progenitor/stem cells such as oval cells. In addition, LDPCs differentiated into functional hepatocytes in vitro as shown by albumin expression and urea production. In conclusion, LDPCs are a population of unique liver progenitors that can be generated from unmanipulated adult liver, which makes them potentially useful for clinical applications, especially for cell transplantation in the treatment of liver diseases.


Capturing the RNA castle: Exploiting MicroRNA inhibition for wound healing.
The growing pipelines of RNA-based therapies herald new opportunities to deliver better patient outcomes for complex disorders such as chronic nonhealing wounds associated with diabetes. Members of the microRNA (miRNA) family of small noncoding RNAs have emerged as targets for diverse elements of cutaneous wound repair, and both miRNA enhancement with mimics or inhibition with antisense oligonucleotides represent tractable approaches for miRNA-directed wound healing. In this review, we focus on miRNA inhibition strategies to stimulate skin repair given advances in chemical modifications to enhance the performance of antisense miRNA (anti-miRs). We first explore miRNAs whose inhibition in keratinocytes promotes keratinocyte migration, an essential part of re-epithelialisation during wound repair. We then focus on miRNAs that can be targeted for inhibition in endothelial cells to promote neovascularisation for wound healing in the context of diabetic mouse models. The picture that emerges is that direct comparisons of different anti-miRNAs modifications are required to establish the most translationally viable options in the chronic wound environment, that direct comparisons of the impact of inhibition of different miRNAs are needed to quantify and rank their relative efficacies in promoting wound repair, and that a standardised human ex vivo model of the diabetic wound is needed to reduce reliance on mouse models that do not necessarily enhance mechanistic understanding of miRNA-targeted wound healing.


Expression and prognostic significance of metalloproteinases and their tissue inhibitors in patients with small-cell lung cancer.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are important in tumor development and progression. MMP expression has been correlated with advanced clinical stage and poor survival in some tumors, but data for small-cell lung cancer (SCLC) are lacking. The aim of this study was to assess the expression of MMPs and TIMPs in SCLC and to evaluate their importance relative to standard prognostic factors. Expression of MMP-1, -2, -3, -9, -11, -13, and -14 and TIMP-1, -2, -3, and -4 was evaluated by immunohistochemistry (IHC). In situ hybridization was used to confirm expression of specific mRNAs. Clinical data collected included sex, tumor stage, performance status, weight loss, hematology (hemoglobin, WBC, platelets) and biochemistry (sodium, albumin, alkaline phosphatase, lactate dehydrogenase), treatment, and survival. Samples from 46 patients were evaluated: 30 males, 16 females; 29 limited, 17 extensive stage; 35 Eastern Cooperative Oncology Group performance status 0-1. Positive IHC staining was evident for MMP-1 and -9 in 60% to 70% of tumor cells, and for MMP-11, -13, and -14 and TIMP-2 and -3 in 70% to 100% of tumor cells. Stromal staining of TIMP-1 to -3 was present in less than 30% of specimens. On multivariate analysis, only stage and decreased tumoral expression of TIMP-1 were significant for response (P =.043). Significant factors for survival were tumor stage (P =.0021); weight loss (P =. 013); and high tumor cell expression of MMP-3 (P =.077), MMP-11 (P =. 031), and MMP-14 (P =.019). MMP and TIMP expression did not differ significantly between stages. MMPs and TIMPs are widely expressed in SCLC. Increased tumoral expression of MMP-3, -11, and -14 were independent negative prognostic factors for survival. The results support the evaluation of synthetic MMP inhibitors in patients with SCLC.


[The effective method of gene transfer into mammalian cells cultured in vitro].
Efficiency of transformation by a number of vectors with the different selective markers of a set of cell lines has been studied for three different methods based on using calcium phosphate, polybrene, or electroporation. Electroporation is shown to be the most efficient one. Using this method with the system rat2k-cells-pAGO vector we have obtained the frequencies of transformation up to 2-3.10(-3). We suggest to use this system as a model for investigation of homologous recombination in the framework of the gene therapy project.


Convenient, inexpensive quantification of elemental sulfur by simultaneous in situ reduction and colorimetric detection.
Rapid, inexpensive, and convenient methods for quantifying elemental sulfur (S(0)) with low or sub-μgg(-1) limits of detection would be useful for a range of applications where S(0) can act as a precursor for noxious off-aromas, e.g., S(0) in pesticide residues on winegrapes or as a contaminant in drywall. However, existing quantification methods rely on toxic reagents, expensive and cumbersome equipment, or demonstrate poor selectivity. We have developed and optimized an inexpensive, rapid method (∼15 min per sample) for quantifying S(0) in complex matrices. Following dispersion of the sample in PEG-400 and buffering, S(0) is quantitatively reduced to H(2)S in situ by dithiothreitol and simultaneously quantified by commercially available colorimetric H(2)S detection tubes. By employing multiple tubes, the method demonstrated linearity from 0.03 to 100 μg S(0) g(-1) for a 5 g sample (R(2)=0.994, mean CV=6.4%), and the methodological detection limit was 0.01 μg S(0) g(-1). Interferences from sulfite or sulfate were not observed. Mean recovery of an S(0) containing sulfur fungicide in grape macerate was 84.7% with a mean CV of 10.4%. Mean recovery of S(0) in a colloidal sulfur preparation from a drywall matrix was 106.6% with a mean CV of 6.9%. Comparable methodological detection limits, sensitivity, and recoveries were achieved in grape juice, grape macerate and with 1g drywall samples, indicating that the methodology should be robust across a range of complex matrices.


Lymphocyte surface membrane immunoglobulin in myeloma. II. T cells with IgA-Fc receptors are markedly increased in mice with IgA plasmacytomas.
BALB/c mice with established subcutaneous IgA plasmacytomas (MOPC-315, MOPC-167, McPC-603, or TEPC-15) develop large numbers of circulating theta-bearing lymphocytes that have surface membrane receptors for IgA. The extraordinary expansion of T alpha cells in mice with IgA plasmacytomas accounts for the large number of lymphocytes with surface membrane myeloma protein that are found in these mice. The IgA myeloma protein that was originally bound to the T cell receptor in vivo was competitively displaced in vitro by other purified IgA myeloma proteins but not by their F(ab)' fragments. After overnight incubation in vitro, or brief exposure to pronase, IgA was released from the T cell surface, rendering available a surface membrane receptor for IgA. In vitro binding of purified IgA to the T alpha cell receptor was not inhibited by purified IgG1 or IgM myeloma proteins. T alpha cells were not increased in mice with three variant plasmacytomas that did not secrete large amounts of IgA. These observations: i) establish the generality of T alpha cell expansion in mice with IgA plasmacytomas, ii) establish an association between elevated serum IgA levels and T alpha cell expansion, and iii) identify a source of large numbers of T alpha cells that can be specifically purified for structural and functional studies.


Glycovariant-based lateral flow immunoassay to detect ovarian cancer-associated serum CA125.
Cancer antigen 125 (CA125) is a widely used biomarker in monitoring of epithelial ovarian cancer (EOC). Due to insufficient cancer specificity of CA125, its diagnostic use is severely compromised. Abnormal glycosylation of CA125 is a unique feature of ovarian cancer cells and could improve differential diagnosis of the disease. Here we describe the development of a quantitative lateral flow immunoassay (LFIA) of aberrantly glycosylated CA125 which is widely superior to the conventional CA125 immunoassay (CA125IA). With a 30 min read-out time, the LFIA showed 72% sensitivity, at 98% specificity using diagnostically challenging samples with marginally elevated CA125 (35-200 U/mL), in comparison to 16% sensitivity with the CA125IA. We envision the clinical use of the developed LFIA to be based on the substantially enhanced disease specificity against the many benign conditions confounding the diagnostic evaluation and against other cancers.


Radiographic progression in children with polyarticular juvenile rheumatoid arthritis: a pilot study.
To assess disease progression on hand/wrist x rays from children with polyarticular juvenile rheumatoid arthritis. Initial and subsequent films of 13 white children (10 girls) were read blind by a paediatric radiologist for the presence of joint space narrowing (JSN), erosions, and relative carpal length (RCL). One child had subcutaneous nodules; one (of 11) was rheumatoid factor positive; six were ANA positive. Median age at diagnosis was 10.7 years (2.5 to 15.9). Median number of involved joints (swelling, pain, or decreased range of motion) at diagnosis was 16 (6 to 33). Four initial x rays had either erosions or JSN. Subsequent x rays were done at (median) 13.3 (8.3 to 24.9) months after initial x rays. One of 10 subsequent x rays had shortened RCL, and six of 13 were worse than the initial ones. Four of these developed new erosions, one had increased number of erosions, and one developed new JSN. About half the children with polyarticular juvenile rheumatoid arthritis will have evidence of radiographic progression within two years after diagnosis. Thus newly diagnosed children are at high risk of substantial joint destruction and potential disability, emphasising the need for prompt treatment.


Testicular microcirculation in the rat studied by videophotometric capillaroscopy, fluorescence microscopy and laser Doppler flowmetry.
Testicular capillary blood flow was studied in rats using laser Doppler flowmetry, in vivo fluorescence microscopy and videophotometric capillaroscopy. All the methods revealed rhythmical oscillations in testicular microcirculation with a periodicity of 4-10 c.p.m. In arterioles, capillaries and small post-capillary vessels, periods of continuous blood flow alternated with periods of no or very low flow. No visible leakage of dextran-150 was observed from the testicular blood vessels. Four, 8 and 16 h after an s.c. injection of 200 IU hCG the blood flow was continuous and there was leakage of dextran-150 from the microvessels to the interstitial tissue. Twenty-four and 32 h after hCG the blood flow pattern was again rhythmical, and at 32 h there was no leakage of dextran-150. This suggests that hCG induces changes in blood flow and transvascular fluid exchange in the testis, perhaps by altering smooth muscle activity at the arteriolar-level.


Isolation and characterization of symbiotic mutants of bradyrhizobium sp. (Arachis) strain NC92: mutants with host-specific defects in nodulation and nitrogen fixation.
Random transposon Tn5 mutagenesis of Bradyrhizobium sp. (Arachis) strain NC92, a member of the cowpea cross-inoculation group, was carried out, and kanamycin-resistant transconjugants were tested for their symbiotic phenotype on three host plants: groundnut, siratro, and pigeonpea. Two nodulation (Nod- phenotype) mutants were isolated. One is unable to nodulate all three hosts and appears to contain an insertion in one of the common nodulation genes (nodABCD); the other is a host-specific nodulation mutant that fails to nodulate pigeonpea, elicits uninvaded nodules on siratro, and elicits normal, nitrogen-fixing nodules on groundnut. In addition, nine mutants defective in nitrogen fixation (Fix- phenotype) were isolated. Three fail to supply symbiotically fixed nitrogen to all three host plants. Surprisingly, nodules elicited by one of these mutants exhibit high levels of acetylene reduction activity, demonstrating the presence of the enzyme nitrogenase. Three more mutants have partially effective phenotypes (Fix +/-) in symbiosis with all three host plants. The remaining three mutants fail to supply fixed nitrogen to one of the host plants tested while remaining partially or fully effective on the other two hosts; two of these mutants are Fix- in pigeonpea and Fix +/- on groundnut and on siratro, whereas the other one is Fix- on groundnut but Fix+ on siratro and on pigeonpea. These latter mutants also retain significant nodule acetylene reduction activity, even in the ineffective symbioses. Such bacterial host-specific fixation (Hsf) mutants have not previously been reported.


Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses.
Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements. Here we describe an approach that combines features of EHM and cardiospheres: Micro-Heart Muscle (μHM) arrays, in which elongated muscle fibers are formed in an easily fabricated template, with as few as 2,000 iPS-CM per individual tissue. Within μHM, iPS-CM exhibit uniaxial contractility and alignment, robust sarcomere assembly, and reduced variability and hypersensitivity in drug responsiveness, compared to monolayers with the same cellular composition. μHM mounted onto standard force measurement apparatus exhibited a robust Frank-Starling response to external stretch, and a dose-dependent inotropic response to the β-adrenergic agonist isoproterenol. Based on the ease of fabrication, the potential for mass production and the small number of cells required to form μHM, this system provides a potentially powerful tool to study cardiomyocyte maturation, disease and cardiotoxicology in vitro.


ROS during the acute phase of Ang II hypertension participates in cardiovascular MAPK activation but not vasoconstriction.
The relations among hypertensive response, oxidative stress, and mitogen-activated protein kinase (MAPK) in cardiovascular tissues have not been fully established. We investigated the involvement of reactive oxygen species on changes in the hemodynamics and cardiovascular MAPKs activities induced by acutely administered angiotensin II (Ang II) in conscious normotensive rats with or without treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol). Intravenous infusion of a pressor dose of Ang II rapidly increased mean arterial blood pressure (MBP) by 53+/-5 mm Hg. After a 30-minute treatment with Ang II, phosphorylated MAPKs (ERK1/2, JNK, p38) as well as thiobarbital reactive substances (T-BARS) were increased in the aorta and cardiac left ventricle. Tempol had no significant effect on the elevation of MBP elicited by Ang II; however, it dose-dependently suppressed the augmented phosphorylation of cardiovascular MAPKs and increased T-BARS levels in plasma and tissues induced by Ang II. An acutely administered pressor dose of phenylephrine, an alpha-adrenoceptor agonist, also showed tempol-sensitive cardiovascular MAPK activation and tempol-insensitive blood pressure elevation. These in vivo data indicate that acute administration of Ang II or phenylephrine provoked an increase in oxidative stress in the cardiovascular tissues leading to the activation of MAPKs, whether it was mediated by pressure overload or the direct action of these vasoconstrictors, and that oxidative stress might not have a major contribution to the acute hypertensive responses elicited by the vasoconstrictors.


Occurrence of tissue cyst forming coccidia in Magellanic penguins (Spheniscus magellanicus) rescued on the coast of Brazil.
The main motivation for this study was to determine the occurrence of Toxoplasma gondii, a cosmopolitan widespread zoonotic parasite distribution that can infect a wide variety of mammals and birds, in Magellanic penguins (Spheniscus magellanicus) in Brazil. In recent decades there has been a significant increase in the number of penguins originating from Argentinian and Chilean Patagonia, where these birds are born, that arrive on the Brazilian coast, where many of them are stranded and rescued. Tissue samples were collected from 330 individuals surveyed from 2012-2015 at the Institute for Marine Animal Research and Rehabilitation (IPRAM) located in Cariacica, state of Espirito Santo, Brazil. Serum were collected from 145 animals surveyed in 2015 for the detection of anti-T. gondii antibodies using the Modified Agglutination Test (MAT ≥20) and 18 birds were positive, with titers of 20 (7 birds), 40 (9 birds) and 80 (2 birds). Mouse bioassay for the isolation of T. gondii was performed using tissues from 54 penguins that were also surveyed in 2015, but no isolates were obtained. DNA from tissue samples of 330 individuals was PCR amplified and sequenced to detect tissue cyst forming coccidians by using pan sarcocystids-directed primers (based on 18S rDNA). These samples were from animals surveyed in 2015 and from frozen stocked tissues from animals surveyed in the years 2012 and 2013. The positives were PCR amplified and sequenced with genus Sarcocystis-specific primers (based on internal transcribed spacer 1, RNA polymerase beta subunit coding gene, and cytochrome B coding gene) and with Sarcocystis falcatula/Sarcocystis neurona- specific primers (based on surface antigens SAG2, SAG3 and SAG4). Sixteen (3.0%) of pectoral muscle samples were positive by all the seven molecular markers and all the samples were identical to each other. Organisms close related to Sarcocystis falcatula were confirmed in all cases. This is the first report on molecular detection of infection by S. falcatula-related organisms and the first report of seropositivity for T. gondii in free-living Magellanic penguins in Brazil. Felids and didephid opossums are definitive hosts of T. gondii and S. falcatula, respectively. Where the penguins acquire the infective forms of the parasites shed by the terrestrial mammals remains to be elucidated.


Catanionic lipid nanosystems improve pharmacokinetics and anti-lung cancer activity of curcumin.
Novel catanionic lipid nanosystems (CLNs) incorporating curcumin (CCM) were developed, and improvements in pharmacokinetics and enhanced anti-lung cancer activity were observed. CCM was present in a lipid matrix surrounded by cationic, anionic and zwitterionic surfactants, forming the core-shell nanosystems. Compared with free CCM, the CCM-CLNs had much higher oral and intravenous bioavailabilities due to enhanced absorption and reduced clearance. The CCM-CLNs exhibited greater cytotoxicity in Lewis lung cancer (LLC) cells, which might have been due to increased antiproliferative, proapoptotic and anti-invasive activities and induction of cell cycle arrest. The CCM-CLNs increased the antitumor efficacy of CCM and decreased the tumor growth rate in tumor-bearing mice. This is the first report of induction of apoptosis in LLC cells by CCM through the PI3K/Akt/FoxO1/Bim signaling pathway. Catanionic lipid nanocarriers show promise for the therapeutic delivery of insoluble anti-tumor drugs.


Sex-Related Online Behaviors, Perceived Peer Norms and Adolescents' Experience with Sexual Behavior: Testing an Integrative Model.
Research on the role of sex-related Internet use in adolescents' sexual development has often isolated the Internet and online behaviors from other, offline influencing factors in adolescents' lives, such as processes in the peer domain. The aim of this study was to test an integrative model explaining how receptive (i.e., use of sexually explicit Internet material [SEIM]) and interactive (i.e., use of social networking sites [SNS]) sex-related online behaviors interrelate with perceived peer norms in predicting adolescents' experience with sexual behavior. Structural equation modeling on longitudinal data from 1,132 Dutch adolescents (M(age) T1 = 13.95; range 11-17; 52.7% boys) demonstrated concurrent, direct, and indirect effects between sex-related online behaviors, perceived peer norms, and experience with sexual behavior. SEIM use (among boys) and SNS use (among boys and girls) predicted increases in adolescents' perceptions of peer approval of sexual behavior and/or in their estimates of the numbers of sexually active peers. These perceptions, in turn, predicted increases in adolescents' level of experience with sexual behavior at the end of the study. Boys' SNS use also directly predicted increased levels of experience with sexual behavior. These findings highlight the need for multisystemic research and intervention development to promote adolescents' sexual health.


Is Central Asia the eastern outpost of the Neandertal range? A reassessment of the Teshik-Tash child.
Since its discovery in southeastern Uzbekistan in 1938, the Teshik-Tash child has been considered a Neandertal. Its affinity is important to studies of Late Pleistocene hominin growth and development as well as interpretations of the Central Asian Middle Paleolithic and the geographic distribution of Neandertals. A close examination of the original Russian monograph reveals the incompleteness of key morphologies associated with the cranial base and face and problems with the reconstruction of the Teshik-Tash cranium, making its Neandertal attribution less certain than previously assumed. This study reassesses the Neandertal status of Teshik-Tash 1 by comparing it to a sample of Neandertal, Middle and Upper Paleolithic modern humans, and recent human sub-adults. Separate examinations of the cranium and mandible are conducted using multinomial logistic regression and discriminant function analysis to assess group membership. Results of the cranial analysis group Teshik-Tash with Upper Paleolithic modern humans when variables are not size-standardized, while results of the mandibular analysis place the specimen with recent modern humans for both raw and size-standardized data. Although these results are influenced by limitations related to the incomplete nature of the comparative sample, they suggest that the morphology of Teshik-Tash 1 as expressed in craniometrics is equivocal. Although, further quantitative studies as well as additional sub-adult fossil finds from this region are needed to ascertain the morphological pattern of this specimen specifically, and Central Asian Middle Paleolithic hominins in general, these results challenge current characterizations of this territory as the eastern boundary of the Neandertal range during the Late Pleistocene.


Endoscopic versus external approach dacryocystorhinostomy: A comparative analysis.
Dacryocystorhinostomy (DCR) consists of creating a lacrimal drainage pathway to the nasal cavity to restore permanent drainage of previously obstructed excreting system. To compare the result and advantages of both endonasal endoscopic and external DCR regarding the patency rate, patient compliance and complications. Prospective non-randomized comparative study. Study was conducted for 16 months duration in a teaching hospital with 50 cases of endoscopic and 30 cases of external DCR with a follow-up of minimum 6 months. Data regarding surgical outcome and complications were analysed and compared using χ(2) test. Total 72 patients were included in the study with six having bilateral involvement, out of which 20 were male and 52 were female. The mean age for endoscopic and external DCR was 33.6 years and 46.0 years, respectively. Right eye (63.8%) was involved more commonly than left eye (36.2%). Epiphora was the commonest presenting symptom (63.7%). Mean duration of surgery was much lengthier in external (mean 119.6 minutes) than endoscopic (mean 49.0 minutes) DCR. Bleeding was the most common immediate postoperative complication seen in 33.3% and 10.0% of external and endoscopic DCR cases, respectively. Primary surgical success rate was 90% and 96.7% for endoscopic and external DCR, respectively (P = 0.046). Among the endoscopic DCR group, four patients underwent revision surgery giving a total successful surgical outcome of 98% at third month of follow-up. However, at 6 month of follow-up, success rate was 92% for endoscopic DCR and 93.3% for external DCR. The difference was not statistically significant (P = 0.609). Intranasal endoscopic DCR is a simple, minimally invasive, day care procedure and had comparable result with conventional external DCR.


Targeting heat shock proteins in tauopathies.
Heat shock proteins are members of a large family that function normally in nascent protein folding and the removal of damaged proteins and are able to respond to cellular stresses such as thermal insult to prevent catastrophic protein aggregation. A number of the most common neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are characterized by such abnormal protein folding and aggregation, and the induction of the heat shock response is observed in these cases through their increased expression and often localization within the inclusions. Tau proteins form the major structural component of the neurofibrillary protein aggregates that correlate with cognitive decline in Alzheimer's disease, and appropriately this abnormal tau is targeted for corrective action by the heat shock proteins that recognize sequence motifs that are normally masked though microtubule binding. This specific heat shock response to the formation of abnormal tau can also be targeted pharmacologically to inhibit the refolding pathways and drive the degradation of tau species that are thought to be pathogenic. This review discusses the recent advances of the roles of heat shock proteins in this process.


Comparison between immigrant and Spanish native-born pathological gambling patients.
The study compared clinical, psychopathological, and personality profiles between immigrants and Spanish native-born pathological gambling patients. A total of 1,601 native-born and 133 immigrant patients attending treatment at a specialized hospital unit were administered a battery of questionnaires during clinical assessment. Outcome measures were compared between both groups and the incremental predictive accuracy of the area of origin was examined using a regression model. Native-born Spaniards showed a mean 2.6 yr. greater duration of the disorder, while immigrants scored higher on South Oaks Gambling Screen, frequency of going to casinos, and total money spent (in a single day and/or to recover losses). General psychopathology and personality scores did not differ between the cohorts. However, immigration from Asia had a statistically significantly incremental validity for pathological gambling in South Oaks Gambling Screen scores. Both cohorts shared more similarities than differences in their gambling profiles.


[Questionnaire survey of patients of medical dental organizations in different regions of the Russian Federation on the issues of individual and professional oral hygiene].
To analyze the respondents' attitudes to oral hygiene and to assess the need for professional oral hygiene in different regions of the Russian Federation based on the data of questionnaire analysis. To obtain comparative data on the issues of individual and professional oral hygiene of patients of medical dental organizations in a number of Russian cities. We conducted an anonymous questionnaire survey of 624 patients (18 to 70 years old) who applied to medical dental organizations of different forms of ownership in five regions of the Russian Federation (Moscow, Omsk, Ryazan, Samara, Tambov). Patients were interviewed using a specially designed questionnaire. The study involved patients of medical dental organizations from 5 regions of the Russian Federation, 57.2% of them were women and 42.8% men. In all cities more than 50% of the surveyed patients received care under the MHI program. More than 50% of the surveyed patients said that they tried to brush their teeth twice a day, the rest of the respondents said that they brushed their teeth only twice a day. Up to 27% of patients are not willing to comply with individualized dental care recommendations for various reasons. Highly motivated patients to high-quality dental hygiene behavior are in minority; according to the results of the study, it can be stated that there is a high need for professional oral hygiene among the surveyed respondents. It is necessary to work with patients to improve hygienic knowledge, skills and motivation for quality oral hygiene.


Multi-Center Retrospective Evaluation of Screw and Polymethylmethacrylate Constructs for Atlantoaxial Fixation in Dogs.
To evaluate outcome and adverse events following ventral stabilization of the atlantoaxial (AA) joint in dogs with clinical AA subluxation using screw/polymethymethacrylate (PMMA) constructs in a retrospective, multi-center cohort study. Historical cohort study. 35 client-owned dogs. Medical records from 3 institutions were reviewed to identify dogs with AA subluxation treated with ventral screw and PMMA constructs. Data on signalment, pre- and postoperative neurologic status, imaging performed, and adverse events were retrieved. Neurologic examination data were abstracted to generate a modified Frankel score at admission, discharge, and re-examination. Telephone interview of owners >180 days postoperative was conducted. Thirty-five dogs with AA subluxation treated with ventral screw/PMMA constructs were included. Most dogs were young (median age 1 year), small breed dogs with acute onset of neurologic signs (median duration 22.5 hours). Most dogs were non-ambulatory at the time of admission (median modified Frankel score 3). Adverse events were identified in 15/35 dogs including 9 dogs with major adverse events. Four dogs required a second surgery due to vertebral canal violation (n = 2) or implant failure (n = 2). Re-examination at 4-6 weeks postoperative reported 15/28 dogs with improved neurologic status and 19/28 dogs were ambulatory. Telephone follow-up was available for 23/35 dogs with 23/23 reported as ambulatory (median follow-up 390 days). Ventral application of screw and PMMA constructs for AA subluxation, as described here, is associated with clinical improvement in the majority of dog. Major adverse events are infrequent and the technique is considered relatively safe.


Prevalence and characteristics of the MMTV-like associated breast carcinomas in Tunisia.
The involvement of a retrovirus homologous to the mouse mammary tumor virus (MMTV) in the pathogenesis of human breast cancer (BC) has long been assumed, but has never been proven. Previous studies have reported the detection of MMTV-like env sequences in variable proportions that did not exceed 40% of BC cases in several countries. However, these viral sequences have been found in higher proportion (74%) in Tunisian diagnosed with BC during the seventies. This study is an attempt to evaluate the current prevalence of MMTV-like env gene in BC in Tunisian women. We used semi-nested PCR that amplify a 190-bp MMTV-like env sequence, followed by direct sequencing to screen a series of 122 cases of BC randomly selected. The findings were correlated to clinicopathological data and immunohistochemical expression status of progesterone and oestrogen receptors, HER2, and P53. Specific MMTV-like env sequences were found in 17 (13.9%) cases of breast carcinomas, whereas the same sequences were not detected in matched normal breast tissues. The presence of the viral sequences correlates inversely with progesterone receptor expression (6.8% versus 20.3%; P=0.03) and HER2 overexpression (3.1% versus 17.7%; P=0.04). This present study confirms the presence of MMTV-like env sequences in BC in Tunisian women but describes an important decrease in the prevalence of the viral sequences compared with previous studies. This reduction may be due to some changes in the virological characteristics or exposure to the virus.


Serum concentrations of formation (PINP) and resorption (Ctx) bone turnover markers in rheumatoid arthritis.
Joint inflammation in rheumatoid arthritis (RA) induces local periarticular osteoporosis. Generalised bone mineral density (BMD) decrease concerns approximately 50% of rheumatic patients. Both types of bone mass depletion can issue from cytokine-induced (TNF-alpha, IL-1, IL-6) osteoclasts' activation, osteoprotegerin and its ligand's (RANKL) function disorders, patients' immobilisation and glucocorticosteroid (GCS) intake, as well as from hormonal alterations in postmenopausal women, predominate among RA individuals. The aim of the study was to compare serum concentrations of marker of bone formation--serum aminoterminal propeptide of type I collagen (PINP), and bone resorption, carboxy (C) terminal telopeptide (Ctx), bone turnover markers in RA and osteoarthritis (OA) patients and in RA groups of different disease activity, different degree of joint damage and the history of GCS intake. A total of 50 RA female patients and 50 women with knee OA were included in the study. Blood for morphology and biochemistry laboratory tests was taken. Joint X-rays to establish OA and RA diagnosis and the degree of RA progression, as well as DEXA BMD measurements were performed. PINP and Ctx concentrations were assessed. In RA patients the number of swollen and painful joints, the duration of morning stiffness, visual analogue scale values and Waaler-Rose's test activity were recorded. The Disease Activity Index (DAS 28) was counted from the appropriate formula. No differences in bone turnover markers' concentrations were noted neither between RA and OA patients nor between the RA group when compared to the one without the history of GCS use. Bone turnover markers' concentrations in RA were proportional to the number of swollen and painful joints. However, no correlation was found between the markers' concentrations and RA activity assessed by DAS 28 or by laboratory means. Ctx concentrations were higher in patients at II degree joint damage according to Larsen and Dale's than at more advanced stages. Ctx concentrations decreased with the disease duration. Serum morphogenesis and resorption markers' concentrations change in course of RA indicating the decrease in bone metabolic activity with the disease duration and progression. High RA activity and severity correlate with increased markers' levels-the resorption one. The influence of GCS on bone metabolism in RA requires further study.


The haemodynamic pathophysiology of pre-eclampsia.
Pre-eclampsia and 'essential' hypertension in pregnancy require to be studied separately. Their haemodynamic characteristics need to be determined and the effects of antihypertensive therapy and blood volume expansion explored. Diuretics should be used in pre-eclampsia only to treat cardiac failure. Hydrallazine may be contraindicated if cardiac failure is imminent. The role of propranolol remains undecided and a controlled trial is required. Studies of the renin-angiotensin system which take into account the various factors that alter renin secretion may prove useful.


PEGylated titanate nanosheets: hydrophilic monolayers with a superior capacity for the selective isolation of immunoglobulin G.
A novel organic-inorganic hybrid was prepared by anchoring (3-aminopropyl)triethoxysilane (APTES) on the surface of monolayer titanate nanosheets and subsequent modification with hydrophilic polyethylene glycol (PEG). The PEGylated hydrophilic monolayer titanate nanosheets were abbreviated as PEG-APTES-TiNSs, and they exhibit a lateral dimension of dozens of nanometers and a thickness of ca. 1.9 nm. PEGylation of the titanate nanosheets significantly improved their selectivity toward the adsorption of glycoproteins through strong hydrophilic interaction, providing an adsorption capacity of 2540.9 mg g-1 for immunoglobulin G (IgG). The retained IgG is readily collected at a recovery rate of 83.4% with 0.5% (m/v) ammonium hydroxide (NH4OH) as the stripping reagent. PEG-APTES-TiNSs are applied for the selective adsorption of IgG from human serum, which is further confirmed by SDS-PAGE assay.


SCreening for Occult REnal Disease (SCORED): a simple prediction model for chronic kidney disease.
Despite the wide availability and low cost of serum creatinine measurement, at-risk populations are not routinely tested for chronic kidney disease (CKD). We used a cross-sectional analysis of a nationally representative, population-based survey to develop a system, SCORED (SCreening for Occult REnal Disease), that uses routinely available demographic and medical information to identify individuals with an increased likelihood of CKD. The analysis included 8530 adult participants in the National Health and Nutrition Examination Surveys conducted from 1999 to 2000 and 2001 to 2002 in the United States. Chronic kidney disease was defined as a glomerular filtration rate less than 60 mL/min per 1.73 m(2). Univariate and multivariate associations between a comprehensive set of risk factors and CKD were examined to develop a prediction model. The optimal characteristics of the model were examined with internal measures. External validation was performed using the Atherosclerosis Risk in Communities study. A model-based numeric scoring system was developed. Age (P<.001), female sex (P = .02), and various health conditions (hypertension [P = .03], diabetes [P = .03], and peripheral vascular disease [P = .008]; history of cardiovascular disease [P = .001] and congestive heart failure [P = .04]; and proteinuria [P<.001] and anemia [P = .003]) were associated with CKD. The multivariate model was well validated in the internal and external data sets (area under the receiver operating characteristic curve of 0.88 and 0.71, respectively). A score of 4 or greater was chosen by internal validation as a cutoff point for screening based on the diagnostic characteristics (sensitivity, 92%; specificity, 68%; positive predictive value, 18%; and negative predictive value, 99%). This scoring system, weighted toward common variables associated with CKD, may be a useful tool to identify individuals with a high likelihood of occult kidney disease.


Sex Disparity in Academic Rank and Industry Payments to Plastic Surgeons.
Despite increasing representation in surgery, women continue to lag behind men in important metrics. Little is known on how industry funding may also contribute to this ongoing disparity. This article seeks to quantify industry payments to academic plastic surgeons (APSs) by sex and examine the relationship between funding and academic achievement. We conducted a cross-sectional analysis of industry payments disbursed to APSs in 2017. Faculty were identified using departmental listings of Accreditation Council for Graduate Medical Education plastic surgery residency programs. Payments were identified via the Center for Medicare and Medicaid Services open payment database. Academic achievement was assessed using rank (eg, assistant professor), leadership designation (eg, division head), and Scopus H-index and then controlled for time in practice. Of the 805 APSs, the majority were male (82% male vs 18% female, P < 0.0001). Significant sex differences emerged in average yearly industry contributions (men, US $3202, vs women, US $707; P < 0.0001). Across all academic ranks, men received significantly higher payments than women (P < 0.0500). Men constituted 93% of full professors and were almost twice as likely to hold additional leadership positions compared with women (odds ratio, 1.82; P = 0.0143). After adjustment for time in practice, there was no difference in H-indices between male and female APSs, although payment disparity persisted (P < 0.0001). Substantial sex-based disparities exist among APSs' academic rank and leadership attainment, which is not attributed to differences in academic qualifications or experience. To better elucidate the sources of this disparity, future studies should assess sexed differences in payment types. Furthermore, we urge for increased transparency in the selection process for industry payments.


Use of a lipid emulsion in a patient with refractory hypotension caused by glyphosate-surfactant herbicide.
Circulatory shock is a major cause of mortality in glyphosate-surfactant herbicide (GlySH) poisoning, and this condition responds poorly to conventional therapies. We report a case of GlySH poisoning with shock that was refractory to vasopressors but responsive to intravenous fat emulsion (IFE). A 52-year-old man was brought to the emergency department by ambulance. He was found unconscious in his living room along with an empty bottle of GlySH herbicide, which contained glyphosate, polyoxyethyleneamine (POEA) surfactant, and water. He was drowsy at presentation. His heart rate was 44 beats/min, his blood pressure could not be measured with an arm cuff, but he had a palpable femoral pulse. After about 2.5 h of supportive care after admission, he remained hypotensive, and his systolic blood pressure was 80 mmHg. A 500 mL bottle of 20% IFE product was prepared. As a bolus, 100 mL of IFE was injected, and the remaining 400 mL was then infused. His blood pressure was 100/60 mmHg 1 h after the bolus injection. At 5 h after IFE injection, his blood pressure reached 160/100 mmHg and vasopressors were tapered. IFE should be considered in cases of refractory hemodynamic instability caused by GlySH after aggressive fluid and vasopressor support.


Brefeldin A blocks an early stage of protein transport in Candida albicans.
Brefeldin A (BFA) inhibited in a dose-dependent manner secretion of the cell-surface enzyme acid phosphatase (APase) into the periplasm of Candida albicans and caused intracellular accumulation of enzyme protein. Cells grown in the presence of BFA became more dense, implying that cell-surface growth was also blocked by BFA treatment. The APase that was accumulated intracellularly migrated faster on SDS-PAGE, suggesting less N-linked glycosylation compared with the mature, periplasmic APase produced in the absence of BFA. Pulse-chase experiments and gel-filtration of oligosaccharides released by Endo H treatment suggested that the core-glycosylated precursor form of APase accumulated in the presence of BFA. These results strongly suggested that endoplasmic reticulum (ER)-to-Golgi transport in C. albicans was inhibited by BFA. Aberrant membrane structures were observed in BFA-treated cells. Within 1 h of BFA removal these structures were replaced with rough ER membranes, suggesting that the accumulated membranes were derived from the ER.


Different storage conditions influence biocompatibility and physicochemical properties of iron oxide nanoparticles.
Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic properties, stability and biocompatibility of the particles. A good knowledge of the effect of storage conditions on those parameters is of utmost importance for the translation of the therapy concept into the clinic and for reproducibility in preclinical studies. Here, core shell SPIONs with a hybrid coating consisting of lauric acid and albumin were stored at different temperatures from 4 to 45 °C over twelve weeks and periodically tested for their physicochemical properties over time. Surprisingly, even at the highest storage temperature we did not observe denaturation of the protein or colloidal instability. However, the saturation magnetisation decreased by maximally 28.8% with clear correlation to time and storage temperature. Furthermore, the biocompatibility was clearly affected, as cellular uptake of the SPIONs into human T-lymphoma cells was crucially dependent on the storage conditions. Taken together, the results show that the particle properties undergo significant changes over time depending on the way they are stored.


A chromatin integration labelling method enables epigenomic profiling with lower input.
Chromatin plays a crucial role in gene regulation, and chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been the standard technique for examining protein-DNA interactions across the whole genome. However, it is difficult to obtain epigenomic information from limited numbers of cells by ChIP-seq because of sample loss during chromatin preparation and inefficient immunoprecipitation. In this study, we established an immunoprecipitation-free epigenomic profiling method named chromatin integration labelling (ChIL), which enables the amplification of genomic sequences closely associated with the target molecules before cell lysis. Using ChIL followed by sequencing (ChIL-seq), we reliably detected the distributions of histone modifications and DNA-binding factors in 100-1,000 cells. In addition, ChIL-seq successfully detected genomic regions associated with histone marks at the single-cell level. Thus, ChIL-seq offers an alternative method to ChIP-seq for epigenomic profiling using small numbers of cells, in particular, those attached to culture plates and after immunofluorescence.


Spillover effects of urban form on urban land use efficiency: evidence from a comparison between the Yangtze and Yellow Rivers of China.
The contradiction between the basin's economic importance and its role as an ecological barrier impedes efficient urban land use. This study aims to propose an integrated approach to compare the urban land use of two representative basin areas of the Yangtze River Economic Belt and the Yellow River Basin and to investigate the impact of urban form on urban land use efficiency. Urban form was characterized by landscape indexes including Patch Density, Largest Patch Index, Edge Density, Patch Cohesion Index, and Agglomeration Index based on FRAGSTATS 4.0 software, and urban land use efficiency was measured by using Slack-Based Model-Undesirable, considering urban land becomes an emission source. Furthermore, spatial econometric models were adopted to explore direct effects and spatial spillover effects of urban form on urban land use efficiency. From 2000 to 2018, changes in urban form in both Yangtze River Economic Belt and Yellow River Basin showed increased fragmentation, enhanced heterogeneity, and more complex patch shapes. The high values of urban land use efficiency were concentrated in lower reaches of the Yangtze and Yellow Rivers. Spatial econometric models suggested that between different basins and various sized cities, the impact of urban form on urban land use efficiency had a spatial spillover effect and regional heterogeneity. Results indicated that input factors such as capital and labor should be more concentrated in metropolitan areas and urban agglomerations, thus promoting higher land use efficiency.


Intramedullary implant stability affects patterns of fracture healing in mice with morphologically different bone phenotypes.
Almost all prior mouse fracture healing models have used needles or K-wires for fixation, unwittingly providing inadequate mechanical stability during the healing process. Our contention is that the reported outcomes have predominantly reflected this instability, rather than the impact of diverse biological conditions, pharmacologic interventions, exogenous growth factors, or genetic considerations. This important issue becomes obvious upon a critical review of the literature. Therefore, the primary aim of this study was to demonstrate the significance of mouse-specific implants designed to provide both axial and torsional stability (Screw and IM Nail) compared to conventional pins (Needle and K-wires), even when used in mice with differently sized marrow canals and diverse genetic backgrounds. B6 (large medullary canal), DBA, and C3H (smaller medullary canals) mice were employed, all of which have different bone morphologies. Closed femoral fractures were created and stabilized with intramedullary implants that provide different mechanical conditions during the healing process. The most important finding of this study was that appropriately designed mouse-specific implants, providing both axial and torsional stability, had the greatest influence on bone healing outcomes regardless of the different bone morphologies encountered. For instance, unstable implants in the B6 strain (largest medullary canal) resulted in significantly greater callus, with a fracture region mainly comprising trabecular bone along with the presence of cartilage 28 days after surgery. The DBA and C3H strains (with smaller medullary canals) instead formed significantly less callus, and only had a small amount of intracortical trabeculation remaining. Moreover, with more stable fracture fixation a higher BV/TV was observed and cortices were largely restored to their original dimensions and structure, indicating an accelerated healing and remodeling process. These observations reveal that the diaphyseal cortical thickness, influenced by the genetic background of each strain, played a pivotal role in determining the amount of bone formation in response to the fracture. These findings are highly important, indicating the rate and type of tissue formed is a direct result of mechanical instability, and this most likely would mask the true contribution of the tested genes, genetic backgrounds, or various therapeutic agents administered during the bone healing process.


Decoupling the influence of systemic variables in the peripheral and cerebral haemodynamics during ECMO procedure by means of oblique and orthogonal subspace projections.
Extra-Corporeal Membrane Oxygenation (ECMO) is a life support system for infants and children with cardio-respiratory failure. During ECMO it is possible to have unstable cerebral haemodynamics, due to strong oscillations in the systemic variables, among other factors, which may lead to brain damage in the patients. Therefore, monitoring the coupling between cerebral haemodynamics and systemic signals might alert us of possible imminent brain damage. In this study we explore the use of orthogonal and oblique subspace projections in the decoupling of these variables, by assessing the ratio between the projections of the haemodynamic variables, onto the subspace spanned by the systemic variables, and the original signals. The coupling of these two systems may differ as different protection mechanisms protect the peripheral system and the brain. Subspace projection was able to decompose the heamodynamic variables as a sum of components related to each systemic variable, separately. As expected, stronger coupling was found between the peripheral haemodynamic and the systemic variables.


Are the alpha 2-adrenoceptors in the noradrenaline cell body region of physiological significance?
Preganglionic stimulation of the cervical sympathetic increased the content of 3,4-dihydroxyphenylacetic acid (DOPAC) in the superior cervical ganglion of rats treated with the dopamine beta-hydroxylase inhibitor FLA-63. It also increased and decreased the concentrations of dopamine and noradrenaline, respectively, in the salivary gland. The effects were partially inhibited by the alpha 2-adrenoceptor agonist clonidine via a yohimbine-sensitive mechanism. The alpha 2-adrenoceptor antagonist yohimbine by itself did not enhance the stimulation-evoked increase in ganglionic DOPAC, but it markedly potentiated the stimulation-evoked changes in dopamine and noradrenaline in the salivary gland. The results indicate that there are inhibitory alpha 2-adrenoceptors both in the somatodendritic and in the axon terminal region of the noradrenaline neurons but that only the alpha 2-receptors of the axon terminals are physiologically stimulated.


LncRNA LINC00689 Promotes the Progression of Gastric Cancer Through Upregulation of ADAM9 by Sponging miR-526b-3p.
Increasing studies have demonstrated that noncoding RNAs, including miRNAs and lncRNAs, have vital roles in mediating cancer progression. However, the expression features and biological functions of LINC00689 in gastric cancer (GC) remain largely unknown. This study was designed to investigate the functions of LINC00689, miR-526b-3p and ADAM9 as well as their interactions in GC. Real time PCR(RT-PCR) was used to detect the expression of LINC0068, miR-526b-3p and ADAM9 in both GC tissues or cell lines. Gain- and loss- of functions of assays were conducted to verify the role of LINC0068, miR-526b-3p and ADAM9 in GC development. Cell proliferation were determined by CCK8 assay and transwell assay and scratch wound-healing assay were used to test cell invasion and migration. Further, the relationships between LINC00689 and miR-526b-3p, miR-526b-3p and ADAM9 were predicted by bioinformatics analysis and then proved by Luciferase reporter assay and RNA Immunoprecipitation(RIP) assay. We found that LINC00689 was upregulated in GC tissues and positively correlated with advanced tumor stage and tumor size, while miR-526b-3p was downregulated. Furthermore, gain- and loss-of-function experiments revealed that LINC00689 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells, while miR-526b-3p had the opposite effects. The underlying mechanisms indicated that LINC00689 functioned as a competing endogenous RNA (ceRNA) by sponging miR-526b-3p in GC cells. Further investigations confirmed that ADAM9 was a direct target of miR-526b-3p and positively modulated the progression of GC. Our study suggests that LINC00689 functions as a novel oncogenic lncRNA in the development of GC by promoting ADAM9 expression through suppression of miR-526b-3p.


Natural polyenic macrolactams and polycyclic derivatives generated by transannular pericyclic reactions: optimized biogenesis challenging chemical synthesis.
Covering from 1992 to the end of 2020-11-20.Genetically-encoded polyenic macrolactams, which are constructed by Nature using hybrid polyketide synthase/nonribosomal peptide synthase (PKSs/NRPSs) assembly lines, are part of the large collection of natural products isolated from bacteria. Activation of cryptic (i.e., silent) gene clusters in these microorganisms has more recently allowed to generate and eventually isolate additional members of the family. Having two unsaturated fragments separated by short saturated chains, the primary macrolactam is posited to undergo transannular reactions and further rearrangements thus leading to the generation of a structurally diverse collection of polycyclic (natural) products and oxidized derivatives. The review will cover the challenges that scientists face on the isolation of these unstable compounds from the cultures of the producing microorganisms, their structural characterization, biological activities, optimized biogenetic routes, as well as the skeletal rearrangements of the primary structures of the natural macrolactams derived from pericyclic reactions of the polyenic fragments. The efforts of the synthetic chemists to emulate Nature on the successful generation and structural confirmation of these natural products will also be reported.


Stem Cell Ribonomics: RNA-Binding Proteins and Gene Networks in Stem Cell Differentiation.
Stem cells are undifferentiated cells with the ability to self-renew and the potential to differentiate into all body cell types. Stem cells follow a developmental genetic program and are able to respond to alterations in the environment through various signaling pathways. The mechanisms that control these processes involve the activation of transcription followed by a series of post-transcriptional events. These post-transcriptional steps are mediated by the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs creating a regulatory gene network. Characterizing these RNA-protein networks is essential to understanding the regulatory mechanisms underlying the control of stem cell fate. Ribonomics is the combination of classical biochemical purification protocols with the high-throughput identification of transcripts applied to the functional characterization of RNA-protein complexes. Here, we describe the different approaches that can be used in a ribonomic approach and how they have contributed to understanding the function of several RBPs with central roles in stem cell biology.


Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients.
Kidney transplant (KTx) recipients should strictly adhere to their lifelong complex therapeutic regimen, and any barriers to medication adherence can weaken correct patient behavior. This study aimed to determine the adherence to immunosuppressive therapy (IS) in KTx adult outpatients in the Czech Republic, and attempted to gain a greater insight into their attitudes toward IS and self-management tasks. Pharmacist-led structured interviews were conducted to assess self-reported adherence to IS using the Czech version of the Medication Adherence Report Scale, in the context of attitudes toward IS in terms of necessity and concern scale of the Beliefs about Medicines Questionnaire. A specific questionnaire was developed to target IS self-management tasks. Medication records were also reviewed for IS serum levels, reflecting direct adherence measurement. Descriptive statistics were used to calculate adherence and self-management variables, and were analyzed by univariate and multivariate correlations, including the decision-tree method. The interview was completed by 211 (male 123; mean age 55.0±12.4 years, mean time 6.6±5.9 years after KTx) of the total of 235 patients. Full adherence to IS was reported by 173 (82.0%) patients. Most of them had IS serum levels within the therapeutic range, however, cyclosporine was associated with the highest variability (P<0.001). Non-adherence and concerns increased over time after KTx (P<0.05). Despite the more common unintentional non-adherence (P<0.001), relatively high concerns signified the risk of not taking IS as prescribed. Concerns also correlated with the perception of impaired health status (P<0.01), as well as the occurrence of IS-related adverse effects (P<0.001). The patients' awareness of their therapy was insufficient, and main gaps in self-management comprised inadequate sun protection, incorrect administration of IS, and unfamiliarity with the IS name, or their indications. Although self-reported adherence to IS therapy was satisfactory, the comprehensive evaluation enabled the detection of greater concerns about IS, as well as underestimated self-management tasks that posttransplant interventions should target in the future.


Embellishments Revisited: Perceptions of Embellished Visualisations Through the Viewer's Lens.
Embellishments are features commonly used in everyday visualisations which are demonstrated to enhance assimilation and memorability. Despite their popularity, little is known about their impact on enticing readers to explore visualisations. To address this gap, we conducted 18 interviews with a diverse group of participants who were consumers of news media but non-experts in visualisation and design. Participants were shown ten embellished and plain visualisations collected from the news and asked to rank them based on enticement and ease of understanding. Extending prior work, our interview results suggest that visualisations with multiple embellishment types might make a visualisation perceived as more enticing. An important finding from our study is that the widespread of certain embellishments in the media might have made them part of visualisation conventions, making a visualisation appear more objective but less enticing. Based on these findings, we ran a follow-up online user study showing participants variations of the visualisations with multiple embellishments to isolate each embellishment type and investigate its effect. We found that variations with salient embellishments were perceived as more enticing. We argue that to unpack the concept of embellishments; we must consider two factors: embellishment saliency and editorial styles. Our study contributes concept and design considerations to the literature concerned with visualisation design for non-experts in visualisation and design.


A new triadic paradigm for osteopathic research in real-world settings.
Clinical research is increasingly conducted in real-world settings. Osteopathic practices represent natural laboratories for studying the distinctiveness of osteopathic medicine. The Osteopathic Research Center (ORC) recently developed a triadic paradigm for research consisting of the Consortium for Collaborative Osteopathic Research Development (CONCORD), its affiliated practice-based research network (PBRN), and the patient-centered research (PCR) fellowship program. The CONCORD-PBRN was certified by the Agency for Healthcare Research and Quality in 2011. The inaugural PCR fellowship class completed didactic training that year. Fellows increased their knowledge of research design and biostatistics following participation in the curriculum. In 2012, a card study of osteopathic palpatory findings and manual techniques will be conducted within the CONCORD-PBRN. The ORC plans to use a hub-and-spoke model to grow the CONCORD-PBRN. Further expansion of this triadic paradigm is dependent on funding streams to support the needed research infrastructure.


Loneliness during the COVID-19 pandemic.
Responses to the COVID-19 pandemic in terms of physical distancing risk collateral damage such as increased loneliness. Older adults have been identified as being at higher risk of poor outcomes if infected and in many countries have been subjected to greater restrictions on physical contacts with others. Most research so far points towards an increase in loneliness during the pandemic. However, there has been a lack of prospective studies based on representative samples of older adults, with the oldest old, older adults with low or no Internet usage, and those in poor health currently underrepresented. Despite the significance of cultural norms for individuals' standards for social relations and, thus, the experience of loneliness, there has been a lack of comparative research on loneliness in older adults during the pandemic. Reviews have found little evidence for what interventions and what elements of interventions are effective in reducing loneliness. There is potential for social relations to be maintained via technology-based solutions, although there is a risk of excluding older adults with limited resources who are both least likely to use technology and most vulnerable to loneliness. Furthermore, remote social contacts cannot fully compensate for the loss of physical contacts. Where stay-at-home orders are not imposed, supporting neighbourliness and the community use of accessible open spaces are other options. Finally, policy responses to the pandemic need to be more nuanced and non-ageist in order to avoid unnecessary increases in loneliness in older adults.


Atrial natriuretic factor inhibits sodium transport in medullary collecting duct.
Characteristics of sodium transport in the inner medullary collecting duct were determined in anesthetized rats before and during intravenous infusion of synthetic atrial natriuretic factor (atriopeptin II). Infusion of the factor was associated with increased sodium delivery and reduced fractional reabsorption in the duct. Increasing delivery to the same extent by KCl infusion had no effect on fractional reabsorption. The results demonstrate that atrial natriuretic factor has a specific inhibitory effect on net sodium transport in this part of the nephron. The mechanism of this inhibition may involve induction of sodium permeability and consequent backflux into the tubular lumen.


Validity of the BPRS, the BDI and the BAI in dual diagnosis patients.
The psychometric properties of the Brief Psychiatric Rating Scale, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were tested in a sample of 134 patients with a substance use disorder and a non-substance related psychiatric disorder in a special inpatient dual diagnosis treatment unit. Subjects were assessed at baseline. At discharge on average 6 months post-intake, 78% of patients were re-assessed using the same instruments. All instruments were tested in (1) their ability to discriminate patients with different diagnoses at baseline and follow-up using comparison of area under the curves, and (2) their temporal stability. Moderator regression was used to test whether thought disorder at baseline had any effect on the test-retest rank-order stability of other instruments. The BPRS Thought Disorder scale was able to discriminate between patients with and without schizophrenia spectrum diagnoses, and the BDI was able to discriminate between patients with and without mood disorders and schizoaffective disorders at intake to treatment, and each instrument was significantly better than the other at discriminating relevant diagnostic groups. Discriminant correlations between the BDI and the BAI were high and statistically significant. Moderator regression analyses showed no indication that any of the scales were less stable at higher levels of thought disorder. It is concluded that dual diagnosis patients can be reliably assessed for symptoms using the BDI and some subscales of the BPRS.


Association of Serum Lipids and Obstructive Lung Disease in Hispanic/Latino Adults of Diverse Backgrounds.
Substantial variation in the prevalences of obstructive lung disease exist between Hispanic/Latino heritage groups. Experimental studies have posited biological mechanisms linking serum lipids and lipid-lowering medications with obstructive lung disease. The aim of this study is to examine the associations of serum lipid levels with the prevalences of asthma and chronic obstructive pulmonary disease in the Hispanic Community Health Study/Study of Latinos and how these associations vary by Hispanic/Latino heritage group. The Hispanic Community Health Study/Study of Latinos is a population-based probability sample of 16,415 self-identified Hispanic/Latino persons aged 18-74 years recruited between 2008 and 2011 from randomly selected households in four US field centers. The baseline clinical examination included comprehensive biological testing (fasting serum lipid levels), behavioral and socio-demographic assessments, medication inventory including inhalers, and respiratory data including questionnaires for asthma and standardized spirometry with post-bronchodilator measures for identification of obstructive lung disease. Hispanic/Latinos with current asthma had lower age- and statin-use-adjusted mean serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels than their non-asthmatic counterparts. In analysis adjusted for age plus gender, ethnicity, cigarette smoking, alcohol intake, body mass index, lipid/cholesterol-lowering medications, age at immigration, health insurance status, and use of oral corticosteroids, increasing serum levels of total cholesterol and low-density lipoprotein cholesterol were associated with lower odds of current asthma in the estimated population. Unlike asthma, Hispanic/Latinos with chronic obstructive pulmonary disease had lower mean high-density lipoprotein than their non- chronic obstructive pulmonary disease counterparts. In the fully adjusted analysis no significant associations were found between lipid levels and prevalent chronic obstructive pulmonary disease. We showed a modest inverse relationship between serum lipid levels and current asthma. These results highlight some important differences in Hispanics/Latinos and certain serum lipids may be factors or markers of obstructive lung disease.


Does visual feedback during walking result in similar improvements in trunk control for young and older healthy adults?
Most current applications of visual feedback to improve postural control are limited to a fixed base of support and produce mixed results regarding improved postural control and transfer to functional tasks. Currently there are few options available to provide visual feedback regarding trunk motion while walking. We have developed a low cost platform to provide visual feedback of trunk motion during walking. Here we investigated whether augmented visual position feedback would reduce trunk movement variability in both young and older healthy adults. The subjects who participated were 10 young and 10 older adults. Subjects walked on a treadmill under conditions of visual position feedback and no feedback. The visual feedback consisted of anterior-posterior (AP) and medial-lateral (ML) position of the subject's trunk during treadmill walking. Fourier transforms of the AP and ML trunk kinematics were used to calculate power spectral densities which were integrated as frequency bins "below the gait cycle" and "gait cycle and above" for analysis purposes. Visual feedback reduced movement power at very low frequencies for lumbar and neck translation but not trunk angle in both age groups. At very low frequencies of body movement, older adults had equivalent levels of movement variability with feedback as young adults without feedback. Lower variability was specific to translational (not angular) trunk movement. Visual feedback did not affect any of the measured lower extremity gait pattern characteristics of either group, suggesting that changes were not invoked by a different gait pattern. Reduced translational variability while walking on the treadmill reflects more precise control maintaining a central position on the treadmill. Such feedback may provide an important technique to augment rehabilitation to minimize body translation while walking. Individuals with poor balance during walking may benefit from this type of training to enhance path consistency during over-ground locomotion.


Surgical Management of Superior Labral Tears in Athletes: Focus on Biceps Tenodesis.
Superior labrum anterior-posterior (SLAP) lesions are common in overhead athletes. Though some patients have asymptomatic lesions, many tears cause pain and diminished athletic performance. Accurate diagnosis of SLAP lesions can be challenging as the sensitivity and specificity of both the physical exam and advanced imaging is questionable. Management is also difficult, as treatment can be life-altering or career-ending for many athletes. If first-line nonoperative treatment fails, surgical options may be considered. The optimal surgical management of SLAP lesions in athletes is debated. Historically, return to play (RTP) rates among athletes who have undergone arthroscopic SLAP repair have been unsatisfactory, prompting clinicians to seek alternate surgical options. Biceps tenodesis (BT) has been postulated to eliminate biceps tendon-related pain in the shoulder and is increasingly used as a primary procedure for SLAP lesions. The purpose of this text is to review the current literature on the surgical management of SLAP lesions in athletes with an emphasis on the role of BT.


Novel Mutations Resulting in a Moderate to Severe Phenotypic Manifestation of Hemophilia A in a Female.
Hemophilia A is an X-linked, recessive disorder resulting from mutations in the f8 gene. Here we report the rare case of a female compound heterozygote with mild factor VIII deficiency (fVIII:C 9%) and moderate phenotype. On investigation she was confirmed to have normal Von Willebrand factor studies with a 46XY genotype. Further genetic testing revealed 3 mutations in the f8 gene: 1 novel missense mutation (c.6142T>G), 1 novel in-frame deletion (c.1281_1292del), and another missense mutation of unclear significance (c.3780C>G). Both parents had normal coagulation profiles; however, the 2 novel mutations were present in the patient's mother and the known missense mutation was present in her father. This unusual case demonstrates the utility in genetic analysis for f8 gene mutational analysis and suggests a compound effect of the 3 identified mutations as a cause for factor deficiency.