Improved myocardial protection by oxygenation of St. Thomas' Hospital cardioplegic solutions. Studies in the rat.
The effect of oxygenation (100% oxygen) of the St. Thomas' Hospital cardioplegic solutions No. 1 (MacCarthy) and No.2 (Plegisol, Abbott Laboratories, North Chicago, Ill.) was examined in the isolated working rat heart subjected to long periods (3 hours for studies with solution No. 1 and 4 hours for studies with solution No. 2) of hypothermic (20 degrees C) ischemic arrest with multidose (every 30 minutes) cardioplegic infusion. At the aortic infusion point the oxygen tension of the oxygenated solutions (measured at 20 degrees C) was in the range of 320 to 560 mm Hg whereas that of the nonoxygenated solutions was less than 150 mm Hg. Twenty hearts (10 oxygenated and 10 nonoxygenated) were studied for each solution. The studies with solution No. 1 demonstrated that oxygenation led to a significant (p less than 0.05) reduction in the incidence of persistent ventricular fibrillation during postischemic reperfusion. Oxygenation of the cardioplegic solution also improved postischemic functional recovery so that the recovery of aortic flow was improved from 18.7% +/- 8.9% (of its preischemic control level) in the nonoxygenated group to 54.6% +/- 6.6% in the oxygenated group (p less than 0.025). Creatine kinase leakage was also significantly reduced from 27.5 +/- 4.8 to 9.9 +/- 0.6 IU/15 min/gm dry weight (p less than 0.005). Studies with solution No. 2 indicated that protection was better than with solution No. 1, even in the absence of oxygenation. A better degree of functional recovery was obtained after 4 hours of arrest with solution No. 2 than that obtained after only 3 hours of arrest with solution No. 1, and persistent ventricular ventricular fibrillation was never observed with solution No. 2. However, despite the superior performance with solution No. 2, further improvements could be obtained by oxygenation, with that time from the onset of reperfusion to the return of regular sinus rhythm being reduced from 55 +/- 8 to 35 +/- 2 seconds (p less than 0.01), postischemic recovery of aortic flow increasing from 59.8% +/- 7.4% to 85.7% +/- 2.5% (p less than 0.005), and creatine kinase leakage being reduced from 38.1 +/- 7.3 to 16.2 +/- 1.5 IU/15 min/gm dry weight (p less than 0.005). It is concluded that oxygenation of the St. Thomas' Hospital cardioplegic solutions improves their ability to protect the heart against long periods of ischemia and that this is manifested by improved postischemic electrical stability, functional recovery, and reduced creatine kinase leakage.


Metabolic syndrome and type 2 diabetes: can we stop the weight gain with diabetes?
Many patients with type 2 diabetes also have the metabolic syndrome with its cardinal features of central adiposity, insulin resistance, dyslipidemia, and hypertension. Although there is strong evidence for the importance of tight glycemic control in minimizing the microvascular complications of diabetes, many of the current therapies used for optimizing glycemic control also cause weight gain. With this treatment-induced weight gain, there is a risk of worsening the patient's insulin resistance. Physicians need to be aware of this vicious cycle in their overweight type 2 diabetic patients. This article reviews the strategies currently available to achieve glycemic control while at the same time minimizing weight gain and the associated complications.


LncRNA TSIX aggravates spinal cord injury by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis.
Long noncoding RNA (lncRNA)-X-inactive-specific transcript (TSIX) expression is upregulated in spinal cord tissues following spinal cord injury (SCI). However, the role of lncRNA-TSIX in SCI remains elusive. SCI animal model was established using C57BL/6 mice. LncRNA TSIX and miR-532-3p expression were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Apoptosis, cell proliferation, and migration were evaluated by transferase dUTP nick end labeling staining, CCK-8, and Transwell assays, respectively. The interaction of miR-532-3p with lncRNA TSIX and DDOST was explored via a dual-luciferase reporter system. Hematoxylin-eosin staining and the Basso, Beattie, and Bresnahan locomotor rating (BBB) scale were performed to investigate SCI progression. The expression of the lncRNA TSIX was found to be significantly upregulated in the serum of SCI patients and spinal cord tissues of SCI mice. The overexpression of lncRNA TSIX enhanced spinal cord neural stem cell (SC-NSC) proliferation and migration in vitro while inhibiting apoptosis and inflammatory cell infiltration in vivo. Moreover, lncRNA TSIX acted as a molecular sponge for miR-532-3p, and the knockdown of miR-532-3p promoted proliferation and migration and inhibited apoptosis of SC-NSCs. Moreover, DDOST was found to be the downstream target of miR-532-3p, and DDOST overexpression showed a similar effect as miR-532-3p silencing on the proliferation, migration, and apoptosis of SC-NSCs. Furthermore, we found that lncRNA TSIX overexpression promoted the activation of the PI3K/AKT signaling pathway. LncRNA TSIX aggravates SCI by regulating the PI3K/AKT pathway via the miR-532-3p/DDOST axis, indicating potential applications for targeted therapy of SCI regeneration.


Comparative analysis of sucrose-embedding for whole-body zebrafish MSI by IR-MALDESI.
Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI) conventionally utilizes fresh-frozen biological tissues with an ice matrix to improve the detection of analytes. Sucrose-embedding with paraformaldehyde fixation has demonstrated feasibility as an alternative matrix for analysis by IR-MALDESI by preserving tissue features and enhancing ionization of lipids. However, investigating multi-organ systems provides broader context for a biological study and can elucidate more information about a disease state as opposed to a single organ. Danio rerio, or zebrafish, are model organisms for various disease states and can be imaged as a multi-organ sample to analyze morphological and metabolomic preservation as a result of sample preparation. Herein, whole-body zebrafish were imaged to compare sucrose-embedding with paraformaldehyde fixation against conventional fresh-frozen sample preparation. Serial sections were analyzed with and without an ice matrix to evaluate if sucrose functions as an alternative energy-absorbing matrix for IR-MALDESI applications across whole-body tissues. The resulting four conditions were compared in terms of total putative lipid annotations and category diversity, coverage across the entire m/z range, and ion abundance. Ultimately, sucrose-embedded zebrafish had an increase in putative lipid annotations for the combination of putative annotations with and without the application of an ice matrix relative to fresh-frozen tissues which require the application of an ice matrix. Upon the use of an ice matrix, a greater number of high mass putative lipid annotations (e.g., glycerophospholipids, glycerolipids, and sphingolipids) were identified. Conversely, without an ice matrix, sucrose-embedded sections elucidated more putative annotations in lower molecular weight lipids, including fatty acyls and sterol lipids. Similar to the mouse brain model, sucrose-embedding increased putative lipid annotation and abundance for whole-body zebrafish.


Evaluation of Knowledge, Attitudes, and Practices Related to Osteoporosis and Correlates of Perceived High Risk among People Living in Two Main Districts of Lebanon.
The prevalence of osteoporosis is increasing in Lebanon. We evaluated the knowledge, attitudes, and practices related to osteoporosis and correlates of its perceived high risk among people living in Beirut and Mount Lebanon districts of Lebanon. This study is a cross-sectional study which consisted of 376 participants that were selected from the two districts within two or three households after two geographical areas were randomly selected from each stratum classified by education and altitude. They were then asked to fill a KAP survey on osteoporosis and provide information on factors likely related to its perceived high risk. The majority of participants had a low (20.2%) and moderate (65.4%) knowledge of osteoporosis, with a higher knowledge in females than in males. A higher percentage of young people perceived it as a serious health risk than that of older people. In contrast, 85.9% participants reported drinking caffeinated beverages and 51.6% participants reported that they do not exercise. Glucose intolerance due to epigenetic and genetic factors, female sex, and older age were risk factors of a perceived high risk of osteoporosis, while any physical exercise, abstention from caffeine for 48 to 72 hours, and higher education were protective factors. A nationwide KAP study should be conducted; likewise, awareness campaigns should be adopted.


Ultrastructure of the Miracidium of Echinostoma paraensei Lie and Basch, 1967 (Trematoda, Echinostomatidae).
The morphology of Echinostoma paraensei was studied using transmission electron microscopy. The terebratorium region has many electrondense secretory granules and many folds on the surface. The epidermal cells that cover the larval body have unique nuclear morphology, many mitochondria and vesicles being attached to the interepidermal ridges by a septate junction. The cilia present the organization 9 + 2 and a typical structure with a shaft, axosome, basal body and rootlet. Below the epidermal cells there is a layer of circular muscle and, adjacent to it, a layer of longitudinal muscle fibers. The excretory system has two flame cells, with internal and external ribs and leptotriches at the barrel region, an excretory vesicle and an excretory pore.


Antitumor activity of hyaluronic acid-selenium nanoparticles in Heps tumor mice models.
In this study, hyaluronic acid-selenium (HA-Se) nanoparticles as novel complexes were synthesized and their antitumor activities in vivo were investigated. The mice inoculated with Heps tumor were orally administered with HA-Se nanoparticles at 86.45 mg/kg (H) and 4.32 mg/kg (L) body weights as high and low doses respectively (2.20% selenium content in the HA-Se nanoparticles samples by ICP-AES) for 10 days. The transmission electron microscopy (TEM) results indicated that the HA-Se nanoparticles were spherical with mean size of 50-70 nm. The HA-Se nanoparticles could significantly reduce tumor weights at the tumor inhibition ratios of 46.92% (H) and 49.12% (L) respectively. However, in the 5-fluorouracil positive group (25 mg/kg), the tumor inhibition ratio was 61.71%. From the study, the HA-Se nanoparticles (4.32 mg/kg) significantly increased thymus and spleen relative weights, enhanced the activities of superoxide dismutase (SOD), reduced the formation of malondialdehyde (MDA) and the activities of aspartate transaminase, alanine transaminase and crea in Heps tumor mice. The results of the study indicated that the HA-Se nanoparticles are potential antitumor candidate for cancer treatment.


Preoperative consolidation-to-tumor ratio and SUVmax stratify the risk of recurrence in patients undergoing limited resection for lung adenocarcinoma ≤2 cm.
Limited resection is an increasingly utilized option for treatment of clinical stage IA lung adenocarcinoma (ADC) ≤2 cm (T1aN0M0), yet there are no validated predictive factors for postoperative recurrence. We investigated the prognostic value of preoperative consolidation/tumor (C/T) ratio [on computed tomography (CT) scan] and maximum standardized uptake value (SUVmax) on (18)F-fluorodeoxyglucose-positron emission tomography (PET) scan. We retrospectively reviewed 962 consecutive patients who underwent limited resection for lung cancer at Memorial Sloan-Kettering between 2000 and 2008. Patients with available CT and PET scans were included in the analysis. C/T ratio of 25 % (in accordance with the Japan Clinical Oncology Group 0201) and SUVmax of 2.2 (cohort median) were used as cutoffs. Cumulative incidence of recurrence (CIR) was assessed. A total of 181 patients met the study inclusion criteria. Patients with a low C/T ratio (n = 15) had a significantly lower 5-year recurrence rate compared with patients with a high C/T ratio (n = 166) (5-year CIR, 0 vs. 33 %; p = 0.015), as did patients with low SUVmax (n = 86) compared with patients with high SUVmax (n = 95; 5-year CIR, 18 vs. 40 %; p = 0.002). Furthermore, within the high C/T ratio group, SUVmax further stratified risk of recurrence [5-year CIR, 22 % (low) vs. 40 % (high); p = 0.018]. With the expected increase in diagnoses of small lung ADC as a result of more widespread use of CT screening, C/T ratio and SUVmax are widely available markers that can be used to stratify the risk of recurrence among cT1aN0M0 patients after limited resection.


Shifting moral values to enhance access to health care: harm reduction as a context for ethical nursing practice.
People who are street involved including those experiencing homelessness and substance use are at increased risk of morbidity and mortality. Such inequities are exacerbated when those facing the greatest inequities in health have the least access to health care. These concerns have rarely been addressed in bioethics and there has been a lack of explicit attention to the dominant societal and organizational values that structure such injustices. The purpose of this paper is to describe the underlying value tensions that impact ethical nursing practice and affect equity in access to health care for those who are street involved. In this paper, findings from a larger qualitative ethnographic study of ethical practice in nursing in the context of homelessness and substance use are reported. The original research was undertaken in two 'inner city' health care centres and one emergency department (ED) to gain a better understanding of ethical nursing practice within health care interactions. Data were collected over a period of 10 months through face-to-face interviews and participant observation. In order to facilitate access to health care for those who are street-involved nurses had to navigate a series of value tensions. These value tensions included shifting from an ideology of fixing to reducing harm; stigma to moral worth; and personal responsibility to enhancing decision-making capacity. A context of harm reduction provided a basis for the development of relationships and shifted the moral orientation to reducing harm as a primary moral principle in which the worth of individuals and the development of their capacity for decision-making was fostered. Implementation of a harm reduction philosophy in acute care settings has the potential to enhance access to health care for people who are street involved. However, explicit attention to defining the harms and values associated with harm reduction is needed. While nurses adopted values consistent with harm reduction and recognized constraints on personal responsibility, there was little attention to action on the social determinants of health such as housing. The individual and collective role of professional nurses in addressing the harms associated with drug use and homelessness requires additional examination.


Groundwater flow and contaminant transport modeling applications in urban area: scopes and limitations.
A three-dimensional groundwater flow model was used to evaluate the groundwater potential and assess the effects of groundwater withdrawal on the regional water level and flow direction in the central Beijing area. A program of groundwater modeling aimed at estimating current contaminant fluxes to the central area and site streams via groundwater was developed. The conceptual model developed for the site attempted to incorporate a complex stratigraphic profile in which groundwater flow and contaminant transport is strongly controlled by a shallow aquifer. Here, a conceptual model for groundwater flow and contaminant transport in central Beijing is presented. Model simulations indicated that a sharp drop in the hydraulic head occurs at the center of the model area, which generates a cone of depression and a continuous decline of head with respect to time as a result of heavy groundwater abstraction.


Structural variability of C3larvin toxin. Intrinsic dynamics of the α/β fold of the C3-like group of mono-ADP-ribosyltransferase toxins.
C3larvin toxin is a new member of the C3 class of the mono-ADP-ribosyltransferase toxin family. The C3 toxins are known to covalently modify small G-proteins, e.g. RhoA, impairing their function, and serving as virulence factors for an offending pathogen. A full-length X-ray structure of C3larvin (2.3 Å) revealed that the characteristic mixed α/β fold consists of a central β-core flanked by two helical regions. Topologically, the protein can be separated into N and C lobes, each formed by a β-sheet and an α-motif, and connected by exposed loops involved in the recognition, binding, and catalysis of the toxin/enzyme, i.e. the ADP-ribosylation turn-turn and phosphate-nicotinamide PN loops. Herein, we provide two new C3larvin X-ray structures and present a systematic study of the toxin dynamics by first analyzing the experimental variability of the X-ray data-set followed by contrasting those results with theoretical predictions based on Elastic Network Models (GNM and ANM). We identify residues that participate in the stability of the N-lobe, putative hinges at loop residues, and energy-favored deformation vectors compatible with conformational changes of the key loops and 3D-subdomains (N/C-lobes), among the X-ray structures. We analyze a larger ensemble of known C3bot1 conformations and conclude that the characteristic 'crab-claw' movement may be driven by the main intrinsic modes of motion. Finally, via computational simulations, we identify harmonic and anharmonic fluctuations that might define the C3larvin 'native state.' Implications for docking protocols are derived.


HCV, HIV AND HBV rapid test diagnosis in non-clinical outreach settings can be as accurate as conventional laboratory tests.
Point of care rapid diagnostic tests (POC-RDT) for Hepatitis C virus (HCV), Human Immunodeficiency virus (HIV) and Hepatitis B virus (HBV), are ideal for screening in non-clinical outreach settings as they can provide immediate results and facilitate diagnosis, allowing high risk population screening. The aim of this study was to compare POC-RDT with laboratory conventional tests. A total of 301 vulnerable evaluable subjects (drug users, migrants and homeless population) were recruited at a mobile screening unit in outreach settings in Madrid. Fingerprick whole blood capillary samples were tested using the SD BIOLINE HCV POC-RDT, Determine HIV Early Detect and Determine HBsAg 2, and the results were assessed against the LIAISON XL HCV, HIV and Murex-HBsAg-Quant, reference assays, respectively. The feasibility and user satisfaction of the POC-RDT were evaluated through a questionnaire. The resolved sensitivity and resolved specificity and their 95% confidence intervals (95% CI) were as follows, respectively: SD-BIOLINE-HCV: 98.8% (95% CI 93.4, 100.0) and 100.0% (95% CI 98.3, 100.0); Determine HIV Early Detect: 100% (95% CI 85.2, 100.0) and 100% (95% CI 98.7, 100); and Determine HBsAg 2: 66.7% (95% CI 9.4, 99.2) and 100.0% (95% CI 98.7, 100.0). As expected, the number of subjects with a confirmed positive result for HBsAg was very low (n = 4). Therefore, the analytical sensitivity has been evaluated in addition: The Determine HBsAg 2 test demonstrated 100% sensitivity for standard concentrations ≥ 0.125 IU/mL. The subject questionnaire yielded positive feedback for most subjects. The POC-RDT fingerprick blood collection method was well received, and the tests demonstrated a comparable clinical performance with conventional tests in outreach settings and vulnerable high-risk populations.


Enhancement of polymorphonuclear leukocyte-mediated tumor cytotoxicity by serum factor(s).
It has been reported that beta-1,3-D-glucan isolated from Alcaligenes faecalis (TAK) promoted tumor cytolysis by mouse polymorphonuclear leukocytes (PMN). We investigated the effect of serum on mouse PMN tumor cytolysis induced by TAK and other PMN stimulators. Addition of fetal calf serum (FCS) to the cytolysis assay enhanced tumor cytolysis by PMN in a dose-dependent manner. Sera obtained from horses, mice, and rats were also effective enhancers of PMN tumor cytolysis. When FCS was added after the assay was under way, the enhancing effect decreased proportionally to the time elapsed. The enhancing activity was detected over a broad range of fractions with a peak at 170 kD by fractionation on a Superose 6 column. The responsible factor(s) in serum was stable after treatment at 60 degrees C, 30 min or after lowering the pH to 2. Mouse PMN stimulated with TAK increased production of hydrogen peroxide in the presence of FCS.


Factors associated with fear-avoidance beliefs about low back pain.
Low back pain (LBP) is a common major health problem. Fear-avoidance beliefs are thought to be an important risk factor for chronic LBP. This study investigated factors associated with the Fear-Avoidance Beliefs Questionnaire (FABQ) scores of Japanese adults who experienced LBP. We focused on the association of FABQ scores with medical advice to rest and the experience of seeing family members and/or significant others with disabling LBP. In February 2011, 1,063,083 adults aged 20-79 years who had registered as internet-based research volunteers were randomly selected and invited to participate in a questionnaire survey. The data from 52,650 respondents who had experienced LBP were analyzed. Multiple linear regression analysis was used to examine the association between FABQ physical activity scores and the advice for respondents with LBP to rest, the experience of seeing others with disabling LBP, and other personal and LBP factors. After controlling for age, sex, and lifetime and current LBP disability grades, the experience of seeing others with disabling LBP (regression coefficient β = 0.94), rest advice (β = 0.91), history of chronic LBP (β = 0.78), radiating pain below the knee (β = 0.44), and workers' compensation (β = 0.51) were associated with higher FABQ physical activity scores. Conversely, regular exercise (β = -0.89) and LBP attributed to sports (β = -0.76) were associated with lower FABQ physical activity scores. The association between rest advice and higher fear-avoidance beliefs supports the recent treatment guidelines that emphasize continuation of daily activities. cross-sectional study.


Cytostatic and tumoricidal activities of tumor necrosis factor-treated neutrophils.
When incubated with recombinant human tumor necrosis factor (TNF), polymorphonuclear neutrophils (PMN) were highly cytostatic to all three tumor cell lines tested. The cytostasis was dose-dependent for both PMN and TNF, and could be neutralized by antibodies specific for TNF. It could also be abrogated by catalase but not by superoxide dismutase (SOD), suggesting that the hydrogen peroxide generated by the TNF-activated PMN was involved in the cytostasis. TNF-treated PMN were also cytotoxic to the tumor cells. However, high level of tumor cytolysis was not evident until after long (greater than 24 h) incubation.


Proton pump inhibitors as also inhibitors of atrial fibrillation.
Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related upper digestive diseases, including gastric and duodenal ulcer and gastroesophageal reflux disease (GERD). Remarkably, several small clinical trials have shown that these drugs also reduce the symptoms and frequency of atrial fibrillation (AF) episodes in patients treated for comorbid acid reflux. Although the mechanism remains unclear, the effect might pinpoint a connection between GERD and AF. To this end, it is known that both oxidants and inflammation affect initiation and maintenance of AF, and PPIs may reduce symptoms and frequency of AF episodes through their antioxidant and anti-inflammatory effects. This review focuses on the anti-AF effects of PPIs beyond their inhibition of gastric acid production.


Predictors and consequences of recurrent laryngeal nerve injury during open thyroidectomy: An American College of Surgeons National Surgical Quality Improvement Project database analysis.
Recurrent laryngeal nerve (RLN) injury is a serious complication of thyroidectomy. The purpose of this study is to determine the predictors and consequences of RLN injury during thyroidectomy. A retrospective analysis was conducted using the ACS-NSQIP 2016-2017 main and thyroidectomy targeted procedure databases. Data was analyzed by multivariate logistic regression resulting in risk-adjusted odds ratios of RLN injury and morbidity/mortality. Age ≥65, black race, neoplastic indication, total or subtotal thyroidectomy, concurrent neck surgery, operation time > median, hypoalbuminemia, and anemia were associated with RLN injury. Use of intraoperative nerve monitoring was associated with decreased RLN injuries. RLN injury is a risk factor for overall morbidity, hypocalcemia, hematoma, pulmonary morbidity, readmission, reoperation, and length of stay > median. Several predictors of RLN injury during thyroidectomy are identified, while use of intraoperative nerve monitoring was associated with a decreased risk of RLN injury. RLN injury is associated increased postoperative complications.


Ten years of clinical results with a tissue-engineered pulmonary valve.
This study was performed to collect prospective safety and effectiveness data from a tissue-engineered heart valve implanted for reconstruction of the right ventricular outflow tract during the Ross operation. From May 2000 until June 2002, 11 consecutive patients, mean age 39.6 ± 10.3 years, received a tissue-engineered heart valve (additive and logistic European System for Cardiac Operative Risk Evaluation, respectively, 3.3 ± 1.3 and 2.8% ± 1.4%). Two to four weeks prior to the Ross operation a piece of forearm vein or saphenous vein was harvested to isolate, characterize, and expand endothelial cells. A cryopreserved pulmonary allograft was decellularized, coated, and seeded with autologous vascular endothelial cells, using a specially developed bioreactor. Cell seeding density was 1.1 × 10(5) ± 0.5 × 10(5) cells/cm(2) with a viability of 93.2% ± 2.1%. All patients survived surgery. Postoperatively no fever of unknown origin was evident. Currently all patients are in New York Heart Association class I. Evaluation of the tissue-engineered heart valve by transthoracic echocardiography showed a mean pressure gradient of 5.4 ± 2.0 mm Hg at 10 years. Multislice computed tomography showed no calcification up to 10 years. Tissue-engineered heart valves showed excellent hemodynamic performance and may prevent degeneration during long-term follow-up.


Water-soluble metal naphthalocyanines--near-IR photosensitizers: cellular uptake, toxicity and photosensitizing properties in NHIK 3025 human cancer cells.
Metal naphthalocyanine complexes (MNCSs) absorb light in the near-IR spectral region (760 nm) where tissue penetration is optimal and they have been proposed as agents for photodynamic therapy (PDT). Sulphonated derivatives of tris-(2,3-naphthalocyanato) bis-chloroaluminium(III) and zinc(II) with various degrees of sulphonation were prepared. Cellular uptake, aggregation in cellular environments, cytotoxicity and photosensitizing properties were studied. Three of the four dyes studied were taken up by cells to a satisfactory degree and were not cytotoxic at the concentration used (10 micrograms ml-1). The least sulphonated sample of zinc naphthalocyanine produced some phototoxic effects (LD50 = 1.12 J cm-2). All the other samples of sulphonated naphthalocyanine were found to be aggregated inside the NHIK 3025 cells, preventing any significant PDT effect.


[The role of steroids in the follicular development in mammals].
The purpose of this review is to know the regulation of ovaric steroidogenesis on follicular development, ovulation and corpora lutea. The modulating endocrine mechanisms involved in the gonadotrophin secretion concomitant with the ovaric steroidogenesis and the follicular develop induce a series of endocrinologic and morphologic events in order to produce a fully mature ovocyte able to be fecundated.


Imatinib induces hypothyroidism in patients receiving levothyroxine.
Interactions of imatinib with other drugs have been scarcely reported. We report a previously unknown effect of imatinib on levothyroxine therapy. Eleven patients (1 with gastrointestinal stromal tumor and 10 with medullary thyroid carcinoma) received imatinib. Eight had undergone thyroidectomy and used levothyroxine, and 3 had the thyroid in situ. Thyroid function was measured before, during, and within 2 weeks after any change in either imatinib or levothyroxine dosage. We observed symptoms of hypothyroidism in all patients who had undergone thyroidectomy, whereas patients with the thyroid in situ remained clinically and biochemically euthyroid. On average, thyrotropin (INN, thyrotrophin) levels increased to 384% +/- 228% of the upper limit in patients after thyroidectomy, whereas free thyroxine (fT4) and free tri-iodothyronine (fT3) values remained within the reference range (59% +/- 17% of the upper limit for fT4 and 63% +/- 4% of the upper limit for fT3). Clinicians should be aware that hypothyroid subjects receiving imatinib have a high likelihood for increased levothyroxine replacement and should be closely monitored for elevations in thyrotropin indicating worsening hypothyroidism.


Survey of total aflatoxins in camels sera by enzyme linked immunosorbent assay (ELISA).
A survey of total aflatoxins was carried out on samples of camels blood sera in order to assess aflatoxin hazards in camels following some deaths among animals during July through September, 1990 in Al Ain area, about 16 km from Abu Dhabi City. Epidemiological and laboratory based studies indicated that the outbreak was associated with the consumption of mould damaged feed.A flavus andA parasiticus and varying amount of aflatoxin were detected in samples tested. 53 samples of camel sera were collected for the analysis: 16 out of 53 samples were collected from apparently clinically healthy racing camels. All these samples were examined for total aflatoxins. All of the 16 samples were found to contain aflatoxins ranging from 5 to 50ng/mL total aflatoxin and 28 out of the 37 samples were found to contain aflatoxin at the range of 2 to 12 pg/mL total aflatoxins.


Association between Antiretroviral Treatment and Markers of Systemic Inflammation among HIV Patients in Ghana.
Studies from high-income countries have reported that even after receiving antiretroviral treatment (ART), HIV-infected adults may not achieve normal levels of certain inflammatory markers that are known to be associated with the onset and development of non-communicable diseases. The aim of this study is to examine the relationship between ART and markers of systemic inflammation in HIV/AIDS patients at an urban antiretroviral clinic in Ghana. We examined serum levels of high sensitivity CRP (hsCRP), interleukin-6 (IL-6), interleukin- 18(IL-18), and tumor necrosis factor-α (sTNFR1 and sTNFR2) from 40 HIV infected patients. Kruskal-Wallis Test was used to examine the differences in markers of systemic inflammation according to the types of ART medication taken. We then utilized generalized additive models (GAM) with non-linear function to examine the association between ART and markers of systemic inflammation after adjusting for potential confounders. Overall, 30 (75.0%) of the participants received ART and 35 (85%) were female. Kruskal- Wallis Test revealed no significant differences in the markers of systemic inflammation among the three categories of ART (none, AZT, 3TC, EFV/NVP, and TDF, 3TC/FTC, EFV/NVP). In the multivariable- adjusted GAM model, we found a significant but non-linear association between time since diagnosis and CRP levels (p=0.006). Although the relatively small sample size limits the scope of the study's findings, these results suggest that individuals on ART need to be screened periodically for the development of chronic conditions. This line of investigation has the potential to influence treatment and clinical guidelines that will improve the quality of care for HIV-infected patients.


Bacteremia and fungemia in patients with neoplastic disease.
This study reviewed 431 episodes of septicemia occurring in 356 patients with cancer at Memorial Sloan-Kettering Cancer Center during 1982. The most frequent organisms causing 273 episodes in 239 non-neutropenic patients were Escherichia coli (20 percent), Staphylococcus aureus (13 percent), polymicrobic (12 percent), Pseudomonas species (8 percent), Klebsiella species (7 percent), Candida species (7 percent), Bacteroides species (6 percent), Enterobacter species (4 percent), and Clostridium species (4 percent). The overall mortality was 31 percent (21 percent with adequate therapy; 50 percent with inadequate therapy). The most frequent organisms causing 158 episodes in 117 neutropenic patients were polymicrobic (21 percent), E. coli (16 percent), Klebsiella species (15 percent), Pseudomonas species (8 percent), Candida species (6 percent), S. aureus (6 percent), Streptococcus faecalis (5 percent), S. epidermidis (4 percent), and Corynebacterium CDC-JK (3 percent). The overall mortality was 52 percent (36 percent with adequate therapy; 88 percent with inadequate therapy). Since a review a decade ago, the spectrum of organisms changed in that the gram-positive organisms, S. faecalis, S. epidermidis, and C. CDC-JK, emerged as important pathogens. Neutropenic patients had a high incidence (42 percent) of septicemia due to multiple organisms, occurring concurrently or sequentially. The overall mortality of these patients was exceptionally high (80 percent). In contrast, the overall mortality of neutropenic patients with single-organism septicemia was comparable to that of non-neutropenic patients with single-organism septicemia (37 percent versus 29 percent).


Differential expression of transforming growth factor-β1 and HBx enhances hepatitis B virus replication and augments host immune cytokines and chemokines.
This study investigated how HBV replication and host immune response are effected by reduced expression of TGF-β1 and HBx. Short interfering RNA (siRNA) knockdown technology has been used to examine the role of TGF-β1 in hepatitis B virus replication. The siTGF-β1 has been transfected along with 1.3mer HBV x-null to investigate the knockdown effect of TGF-β1 on HBV replication and host immune factors. In this study, we found that diminished expression of TGF-β1 and increased expression of HBx enhances HBV replication several folds. The differential expression of TGF-β1 and HBx also stimulated transcriptional viral replicative intermediate (pgRNA) and secretion of core and 'e' antigen at translational level. Consequently, several cytokines such as IL-2, IL-8 and chemokine monocyte- chemoattractant protein (MCP-1) were increased significantly in response to stimulation of HBV replication. In contrast, TNF-α and RANTES mRNA expression increased insignificantly in response to enhanced HBV replication. We concluded that reduced expression of TGF-β1 together with HBx expression stimulate HBV replication and immune response, although the underlying mechanism of stimulation most likely differs.


Determinants of epigenetic resistance to HDAC inhibitors in dystrophic fibro-adipogenic progenitors.
Pharmacological treatment of Duchenne muscular dystrophy (DMD) with histone deacetylase inhibitors (HDACi) is currently being tested in clinical trials; however, pre-clinical studies indicated that the beneficial effects of HDACi are restricted to early stages of disease. We show that FAPs from late-stage mdx mice exhibit aberrant HDAC activity and genome-wide alterations of histone acetylation that are not fully reversed by HDACi. In particular, combinatorial H3K27 and/or H3K9/14 hypo-acetylation at promoters of genes required for cell cycle activation and progression, as well as glycolysis, are associated with their downregulation in late-stage mdx FAPs. These alterations could not be reversed by HDACi, due to a general resistance to HDACi-induced H3K9/14 hyperacetylation. Conversely, H3K9/14 hyper-acetylation at promoters of Senescence Associated Secretory Phenotype (SASP) genes is associated with their upregulation in late-stage mdx FAPs; however, HDACi could reduce promoter acetylation and blunt SASP gene activation. These data reveal that during DMD progression FAPs develop disease-associated features reminiscent of cellular senescence, through epigenetically distinct and pharmacologically dissociable events. They also indicate that HDACi might retain anti-fibrotic effects at late stages of DMD.


Pretreatment with a gonadotropin-releasing hormone agonist and an aromatase inhibitor may improve outcomes in in vitro fertilization cycles of women with stage I-II endometriosis.
To determine whether 2 months of pretreatment with 5 mg of letrozole daily plus leuprolide acetate at 3.75 mg monthly in women with laparoscopically confirmed American Society of Reproductive Medicine stage I-II endometriosis improves in vitro fertilization (IVF) outcomes. Prospective cohort study. University-affiliated tertiary hospital. Women with laparoscopically confirmed endometriosis treated in the period from 2012 to 2016. None. Primary outcomes: clinical pregnancy and live-birth rate; secondary outcomes: stimulation parameters and pregnancy. A total of 68 patients were included in the final analysis. Thirty-six women received a gonadotropin-releasing hormone (GnRH) agonist and an aromatase inhibitor (AI), and 32 women received a GnRH agonist alone. The women did not differ in mean age, antral follicle count, basal serum level of follicle-stimulating hormone, or previous pregnancies. The stimulation parameters were similar between both groups: gonadotropin dose, number of collected oocytes, number of blastocysts. All women underwent a single blastocyst transfer. The grade of embryos transferred did not differ. Clinical pregnancy (24 [66.7%] vs. 13 [40.6%]) and live-birth (22 [61.1%] vs 10 [31.3%]) rates improved with aromatase inhibitor added to the GnRH agonist treatment versus a GnRH agonist alone. In this study, we present the first comparison in the medical literature comparing IVF outcomes in women with minimal and mild endometriosis pretreated with a GnRH agonist with or without an AI. This prospective cohort study suggests that combining these two treatment modalities which work at different sites may improve pregnancy outcomes with IVF treatment.


Does parasternal irradiation reduce thoracic vertebral metastases in breast cancer?
A review of 197 patients with bone metastases from breast carcinoma was undertaken to assess the effect of adjuvant parasternal irradiation on the distribution of those metastases. A total of 128 patients (Group I) received radiation. The control group consisted of 69 patients (Group II) who did not receive adjuvant radiation. The dose absorbed by the mid-thoracic vertebrae (T3 to T8) varied from 10 Gy in 3 weeks to 20 Gy in 4 weeks. The distribution of bone metastases was analyzed at the initial development in the 197 patients. Repeat assessments (X ray/scans) were available for analysis in 132 patients. Patients in Group I had less metastases from T3 to T8: 37/128 (29%), vs 30/69 (43.5%) for patients in Group II: (chi 2 = 3.62; p less than 0.10). For the 132 patients with serial assessments, the difference at last evaluation was more significant: 45/86 (52%) in Group I, vs 36/46 (78%) in Group II: (chi 2 = 7.44; p less than 0.01). The data shows that patients receiving low-dose exit beam irradiation from the parasternal field have fewer mid-thoracic bone metastases. Potential implications are discussed.


Differential effects of inferior temporal cortex lesions upon visual and auditory-evoked potentials in the amygdala of the squirrel monkey (Saimiri sciureus).
Visual-evoked potentials (VEPs) and auditory-evoked potentials (AEPs) were elicited from amygdala nuclei and inferior temporal (IT) cortex in chaired, alert squirrel monkeys to diffuse flash and click stimuli. VEPs were recorded from electrodes placed in basalis lateralis amygdalae (BLA) and basalis medialis amygdalae (BMA) while AEPs could also be obtained from additional electrode sites in basalis accessorius medialis (BAM), centralis amygdalae (CeA), and lateralis amygdalae (LA). The amygdala-evoked potentials resulting from stimulation of the two modalities were similar in terms of component configuration. AEPs recorded from the IT cortex had shorter latencies than the amygdala VEPs that were recorded. Both modalities of stimulation elicited potentials with shorter onset latencies in the amygdala than those recorded from the surface of IT cortex. Bilateral ablation of the IT cortex eliminated VEPs recorded from the BMA but not the BLA amygdala region. AEPs recorded from BMA as well as other amygdala areas were not consistently affected by these IT cortical ablations.


Genetics in Light of Transcriptional Adaptation.
Genetics has recently benefited from the genome engineering revolution: genes can be knocked out, knocked down, or activated more easily than ever before. This range of genetic manipulations has also provided a range of outcomes, sometimes contradictory. But how much interesting biology hides within these discrepancies? Recent studies have shown that genetic compensation can be activated by some gene perturbations and not others, hinting that this phenomenon might skew our understanding of the genotype-phenotype relationship. We review the main findings regarding transcriptional adaptation, a newly discovered form of genetic compensation, and discuss their possible implications for establishing and analyzing animal and plant models to study gene function. We also touch upon how this new knowledge could benefit our understanding of disease-causing mutations and help explain cases of low penetrance or variable expressivity in human genetics.


Diet quality partially mediates the association between ultraprocessed food consumption and adiposity indicators.
This study evaluated the potential role of overall diet quality in the associations between ultraprocessed food (UPF) consumption and adiposity indicators among Korean adults. Baseline data of participants (n = 4331) of the Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort study were obtained. Dietary information was collected by a validated food frequency questionnaire. UPF was defined using the NOVA classification. Overall diet quality was assessed using the Korean Healthy Eating Index. Adiposity indicators included BMI, waist circumference, percentage body fat by bioimpedance, and visceral fat mass by whole-body dual-energy x-ray absorptiometry. Mediation analysis after adjustment for potential confounders was performed. UPF intake was associated with higher adiposity indicators after adjustment for confounders. The mediating effect of the Korean Healthy Eating Index on the relationship between UPF consumption and each adiposity indicator was 35.6% (95% CI: 4.9% to 255.9%) for BMI, 38.3% (17.9% to 132.1%) for waist circumference, 40.2% (8.3% to 259.4%) for percentage body fat, and 60.7% (-396.4% to 662.7%) for visceral fat mass. UPF consumption was positively associated with adiposity indicators, which were partially attributed to the overall diet quality. Further studies are needed to better understand the causal mechanisms of these associations.


White matter integrity and functional connectivity in adolescents with a parental history of substance use disorder.
A family history (FH+) of substance use disorder (SUD) increases an adolescent's risk for substance use initiation and progression. Greater impulsivity and reward seeking behavior is known to be associated with such risk. At the neurological level, dysfunction of cortico-striatal and cortico-limbic pathways have been proposed as contributors to the increased SUD risk in adolescents with FH+. In addition, disadvantaged environments have been associated with atypical brain connectivity and higher SUD risk. However, it remains unclear if this increased risk is manifested in structural and functional brain abnormalities prior to regular drug use. To examine this, we employed complementary imaging of structural and functional connectivity of 60 FH+ and 55 FH- minority adolescents, all from families with low socio-economic status. We acquired diffusion tensor-imaging (DTI) and resting state fMRI data across the whole brain. Structural connectivity was examined by measuring fractional anisotropy (FA) using DTI, to indicate integrity of the white matter tracts. Functional connectivity within and between resting state networks was assessed by the correlation of blood-oxygen-level-dependent (BOLD) signal between intra and inter-network nodes. Psychological measures of impulsivity and reward seeking were also obtained with standardized measures, the BIS-11 and the BIS/BAS, and their association with FA and functional connectivity was evaluated. We found no differences in white matter integrity between the groups. Compared to FH-, FH + adolescents showed significantly greater functional connectivity between posterior regions of the Default Mode Network (DMN) and the Fronto-Parietal Network (FPN). While psychological measures of reward seeking behavior did not differ between the FH+ and FH- groups, impulsivity, assessed by the BIS-11, was significantly higher for FH+. However, we did not find significant differences between the FH+ and FH- groups when comparing associations of BIS-11 scores and white matter integrity or functional connectivity measures. The stronger inter-network functional connectivity between the DMN and FPN in FH + adolescents suggests that transmitted risk for SUD may be related to large-scale brain dynamics. The lack of structural differences support the importance of early prevention efforts for FH + adolescents, before initiation of drug use, allowing for healthy brain development.


Dietitians and Nutritionists: Stigma in the Context of Obesity. A Systematic Review.
Negative attitudes towards people with obesity are common even in health care settings. So far, the attitudes and causal beliefs of dietitians and nutritionists have not been investigated systematically. The aim of this article was to review the current state of quantitative research on weight-related stigma by dietitians and nutritionists. A systematic literature review was conducted in 2014 using PubMed, PsycINFO, Web of Science and Cochrane Library. Eight studies were found that differ in regard to study characteristics, instruments and the origin of the sample. Six out of eight studies reported weight stigma expressed by dietitians and nutritionists. Their believed causes of obesity indicated a defined preference for internal factors rather than genetics or biology. Results of studies were not homogenous. The degree of negative attitudes by dietitians and nutritionists towards people with obesity appeared to be slightly less pronounced compared to the general public and other health care professionals. Stigma and its consequences should be included into educational programs to optimally prepare dietitians and nutritionists.


Contraceptive patterns and premarital pregnancy among women aged 15--19 in 1976.
About 780,000 teenagers experience a premarital pregnancy each year. If they weren't using contraception, an additional 680,000 would become pregnant--a total of 1,460,000. However, if all who did not want a baby were practicing contraception consistently, we could reduce the number of pregnancies by at least 313,000. Only 467,000 would become pregnant, and half of these pregnancies would be wanted.


Personal Protective Equipment: Protecting Health Care Providers in an Ebola Outbreak.
The recent Ebola epidemic that devastated West Africa has infected and killed more health care providers than any other outbreak in the history of this virus. An improved understanding of pathogen transmission and the institution of strategies to protect health care providers against infection are needed in infectious disease outbreaks. This review connects what is known about Ebola virus transmission with personal protective equipment (PPE) designed to arrest nosocomial transmission. Articles pertaining to filovirus transmission and PPE in filovirus outbreaks were reviewed and findings are presented. In addition, studies that evaluated PPE and donning and doffing strategies are presented. PPE is one step in a comprehensive infection prevention and control strategy that is required to protect health care providers. Given that the Ebola virus is primarily transmitted through direct contact of mucous membranes and cuts in the skin with infected patients and/or their bodily fluids, it is necessary to cover these potential portals of infection with PPE as part of a structured and instructed donning and doffing procedure. Current recommendations about PPE and the donning and doffing processes are based on anecdotal experience. However, the use of non-human viruses can help provide evidence-based guidelines on both PPE and donning and doffing processes.


Metabolic cooperation in aggregates of embryonal carcinoma cells.
Metabolic cooperation may be associated with the processes of compaction and subsequent differentiation in aggregates of embryonal carcinoma cells (ECC). To determine if the gap junctions present in loose and compacted aggregates of H6 ECC are active in metabolic cooperation, aggregates of each type containing a mixture of 5-bromodeoxyuridine- and 6-thioguanine-resistant H6 cells were exposed to HAT medium, 6-thioguanine, or [3H]thymidine. These three methods indicated that some crossfeeding occurred through the small clusters of gap junctions in loose aggregates and more crossfeeding occurred through the larger clusters of gap junctions in compacted aggregates.


NPGPx-Mediated Adaptation to Oxidative Stress Protects Motor Neurons from Degeneration in Aging by Directly Modulating O-GlcNAcase.
Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, usually occurs in middle-aged people. However, the molecular basis of age-related cumulative stress in ALS pathogenesis remains elusive. Here, we found that mice deficient in NPGPx (GPx7), an oxidative stress sensor, develop ALS-like phenotypes, including paralysis, muscle denervation, and motor neurons loss. Unlike normal spinal motor neurons that exhibit elevated O-GlcNAcylation against age-dependent oxidative stress, NPGPx-deficient spinal motor neurons fail to boost O-GlcNAcylation and exacerbate ROS accumulation, leading to cell death. Mechanistically, stress-activated NPGPx inhibits O-GlcNAcase (OGA) through disulfide bonding to fine-tune global O-GlcNAcylation. Pharmacological inhibition of OGA rescues spinal motor neuron loss in aged NPGPx-deficient mice. Furthermore, expression of NPGPx in ALS patients is significantly lower than in unaffected adults. These results suggest that NPGPx modulates O-GlcNAcylation by inhibiting OGA to cope with age-dependent oxidative stress and protect motor neurons from degeneration, providing a potential therapeutic axis for ALS.


Differences between alcoholic and non alcoholic female psychiatric patients.
Sixty-four consecutive DSM-III alcoholic female psychiatric patients (A-group) were compared with 65 non alcoholic women from the same psychiatric units. The A-women more often had nervous sisters. They were younger at the first intercourse, had had more frequent intercourses during the last year, more often had a poor relationship with their children. They had had more heterosexual partners, living-together relationships and divorces, and had more often a dependent adult relationship. The mean age of the first nervous symptoms and of coming to psychiatry was significantly lower in the A-group, and they had more suicidal attempts and criminality. During childhood, adolescence and adult age, they reacted more often to losses with acting out and alcohol abuse. Nervous problems and close contact difficulties seem to have manifested themselves mostly before the alcohol abuse was established.


Steppogenin suppresses tumor growth and sprouting angiogenesis through inhibition of HIF-1α in tumors and DLL4 activity in the endothelium.
Hypoxia is a characteristic feature of many solid tumors. As an adaptive response to hypoxia, tumor cells activate hypoxia-inducible factor-1α (HIF-1α). Under hypoxic conditions, angiogenesis mediated by HIF-1α is involved in the growth and metastasis of tumor cells. During the angiogenic process, differentiated tip endothelial cells (ECs) characterized by high expression of DLL4 promote angiogenic germination through filopodia. Inhibitors of HIF-1α or DLL4 have been widely studied PURPOSE: We tried to find inhibitors targeting both HIF-1α and DLL4 in tumor which have not yet been developed. In this study, we examined a natural compound that inhibits sprouting angiogenesis and tumor growth by targeting both HIF-1α and DLL4 under hypoxic conditions. After examining cell viability of 70 selected natural compounds, we assessed the effects of compounds on HIF-1α and DLL4 transcriptional activity using a dual-luciferase reporter assay. Western blot analysis, immunofluoresecnt assay and real-time qPCR were performed to identify expression of proteins, such as HIF-1α and DLL4, as well as HIF-1α target genes under hypoxic conditions. In vitro angiogenesis assay and in vivo allograft tumor experiment were performed to investigate inhibition of tumor growth through anti-angiogenic activity. Among these compounds, steppogenin, which is extracted from the root bark of Morus alba l, respectively inhibited the transcriptional activity of HIF-1α under hypoxic conditions in HEK293T cells and vascular endothelial growth factor (VEGF)-induced DLL4 expression in vascular ECs in a dose-dependent manner. In tumor cells and retinal pigment epithelial cells, steppogenin significantly suppressed HIF-1α protein levels under hypoxic conditions as well as VEGF-induced DLL4 expression in ECs. Furthermore, steppogenin suppressed hypoxia-induced vascular EC proliferation and migration as well as VEGF-induced sprouting of EC spheroids. These results suggest that the natural compound steppogenin could potentially be used to treat angiogenic diseases, such as those involving solid tumors, because of its dual inhibition of HIF-1α and DLL4.


Induction and decline of HPRT mutants and deletions following a low dose radiation exposure at Chernobyl.
This study was conducted to evaluate the ability of mutation in the hypoxanthine-phosphoribosyltransferase gene (HPRT) to detect radiation-induced mutation in lymphocytes of Russian Chernobyl Clean-up workers, particularly as a function of time after exposure. It is part of a multi-endpoint study comparing HPRT mutation with chromosome translocation and glycophorin A mutation [Radiat. Res. 148 (1997) 463], and extends an earlier report on HPRT [Mutat. Res. 431 (1999) 233] by including data from all 9 years of our study (versus the first 6 years) and analysis of deletion size. Blood samples were collected from 1991 to 1999. HPRT mutant frequency (MF) as determined by the cloning assay was elevated 16% in Clean-up workers (N=300, the entire group minus one outlier) compared to Russian Controls (N=124) when adjusted for age and smoking status (P=0.028). Since exposures occurred over a short relative to the long sampling period, the year of sampling corresponded roughly to the length of time since exposure (correlation coefficient=0.94). When date of blood sample was considered, Control MF was not time dependent. Clean-up worker MF was estimated to be 47% higher than Control MF in 1991 (P=0.004) and to decline 4.4% per year thereafter (P=0.03). A total of 1123 Control mutants and 2799 Clean-up worker mutants were analyzed for deletion type and size by PCR assay for retention of HPRT exons and flanking markers on the X chromosome. There was little difference between the overall deletion spectra of Clean-up workers and Controls. However, there was a decline in the average size of deletions of Clean-up workers as time after exposure at Chernobyl increased from 6 to 13 years (P< or =0.05). The results illustrate the sensitivity of HPRT somatic mutation as a biomarker for populations with low dose radiation exposure, and the dependence of this sensitivity on time elapsed since radiation exposure.


Effect of dopamine on electrical activity of isolated stomach muscle in cats.
The effect of dopamine on electrical activity (gastric slow wave) of the stomach was studied in isolated stomach muscle strips of 145 cats. The gastric slow wave was recorded by four monopolar electrodes (Ag-AgCl) in Krebs-Ringer solution (pH 7.4, temperature 36 +/- 0.5 degrees C) bubbled with 5% CO2 in O2. Dopamine induced concentration-dependent alterations in frequency and propagation of slow waves. Development of irregular propagation was significantly suppressed by domperidone pretreatment. The variation of dopamine-induced slow-wave frequency was significantly inhibited by domperidone and phentolamine but not by propranolol, hexamethonium, and tetrodotoxin. The study indicates that a dopamine receptor exists in the stomach and plays a role in the genesis of gastric electrical abnormality.


Yes-associated protein inhibition ameliorates liver fibrosis and acute and chronic liver failure by decreasing ferroptosis and necroptosis.
This study aims to determine which cell death modes contribute most in the progression of cirrhosis and acute-on-chronic liver failure (ACLF), and to investigate whether Yes associated protein (YAP) affects the disease process by regulating cell death. 30C57BL/6 male mice were divided into five groups: control, carbon tetrachloride (CCl4)-induced liver fibrosis model, CCl4+verteporfin, CCl4+lipopolysaccharides (LPS) combined with the D-(+)-Galactosamine (LPS/D-GalN)-induced ACLF model, and ACLF + verteporfin. Patients with chronic hepatitis B (CHB), hepatitis B virus (HBV) related liver cirrhosis or ACLF were enrolled. Histology, immunohistochemistry, transmission electron microscopy, Western blot and ELISA were conducted to assess the roles of YAP and cell death in liver cirrhosis and ACLF, and to explore the effect of YAP inhibition on cell deaths. YAP was markedly increased in mice with liver fibrosis and ACLF, along with ferroptosis and necroptosis. Furthermore, YAP inhibition significantly suppressed fibrosis in CCl4-mediated liver fibrosis and ACLF-associated liver injury. Notably, CCl4 induced up-regulation of ACSL4 and RIPK3 and down-regulation of SLC7A11, key factors in ferroptosis and necroptosis. This was significantly abrogated by verteporfin treatment. Similar changes in ferroptosis and necroptosis were found in ACLF and ACLF + verteporfin groups. Consistent with the above findings in mice, we found that plasma YAP levels were gradually increased with the development of HBV-related liver fibrosis and ACLF. Ferroptosis and necroptosis are involved in the development of liver cirrhosis and ACLF. Inhibition of YAP improved liver fibrosis and liver damage in ACLF through a reduction in ferroptosis and necroptosis. Our findings may help better understanding the role of YAP in liver fibrosis and ACLF.


Microcornea associated with myopia.
The presentation of microcornea associated with axial myopia by means of modern examination techniques. Clinical investigations. The horizontal diameter of the cornea was 8.00 mm on both sides. The average refractive power of the cornea was 39.27D/38.48D on the right/left sides by corneal topography. The central corneal thickness was 568 micro m/559 micro m on the right and left sides, respectively. The depth of the anterior chamber was 1.18 mm/1.14 mm and the origin of the irises was steep, as demonstrated by ultrasound biomicroscopy (UBM). The axial length was 26.42 mm/25.63 mm on the right/left sides. Endothelial morphology disclosed degeneration on both sides. The present case demonstrates that the clinical signs of microcornea are flat corneal surface, normal thickness, and degenerated endothelium. This disorder associated with axial myopia is an extremely rare ophthalmologic condition.


Regional nerve blocks of the face.
Regional nerve blocks of the face are important skills every emergency physician ought to know. Facial anesthesia improves cosmetic outcomes, reduces pain, and improves patient satisfaction. Understanding the anatomy of the head and face is essential to the application of regional anesthesia, and this anatomy will be reviewed in depth. By completion of this article, physicians should appreciate the basics of the various nerve blocks of the head and face to repair any laceration.


Pharmacological basis of tanshinone and new insights into tanshinone as a multitarget natural product for multifaceted diseases.
Drug development has long included the systematic exploration of various resources. Among these, natural products are one of the most important resources from which novel agents are developed due to the multiple pharmacologic effects of these natural products on diseases. Tanshinone, a representative natural product, is the main compound extracted from the dried root and rhizome of Salvia miltiorrhiza Bge. Research on tanshinone began in the early 1930s. With the in-depth investigation of an increasing number of identified analogs, tanshinone has demonstrated a wide variety of bioactivities and contradicted the saying, 'You can't teach an old dog new tricks'. This review is focused on the pharmacological action of tanshinone and status of research on tanshinone in recent years. The mechanism of tanshinone has also drawn much attention, with the findings of representative targets and pathways of tanshinone. The most recent studies have comprehensively shown that tanshinone can be used to treat leukemia and solid carcinoma, protect against cardiovascular and cerebrovascular diseases, and alleviate liver- and kidney-related diseases, among its other effects. Multiple signaling pathways, including antiproliferative, antiapoptotic, anti-inflammatory, and antioxidative stress pathways, are involved in its actions.


The nature of the attachment of a regularly arranged surface protein to the outer membrane of an Acinetobacter sp.
Acinetobacter 199A carries on the outer surface of its outer membrane a layer of regularly arranged protein subunits. The isolated surface protein assembles into the same regular array even in the absence of the underlying outer membrane. Cl- minus is required for this self-assembly. Evidence is presented that the interaction of the surface protein with the outer membrane involves the linking of a carboxyl group in the surface protein to a negatively charged group in the outer membrane protein, via a divalent cation. The surface protein could be detached from the outer membrane by the protein perturbant urea, by the chelating agent EDTA and by replacing Mg-2+ with Na+. It could not be detached by treatment with phospholipases A anc D or the detergents Tween 80 and sodium deoxycholate. The conditions favourable for reattachment of surface protein to the cell wall were the presence of divalent cations and a pH of 3-5. Conversion of carboxyl groups in the surface protein to amine with carbodiimide and ethylene diamine interfered with reattachment. The surface protein did not attach to isolated cell wall lipid or lipopolysaccharide.


Study on the effect of medicinal leech therapy (Hirudo medicinalis) on full-thickness excisional wound healing in the animal model.
The possible impacts of alternative and conventional medicines on wound healing are now of growing interest. This study aimed to evaluate and elucidate the wound healing activity of medicinal leech therapy in wound excision of the rat model. After a round, full-thickness excision was made in the dorsal region of the body, the animals (n = 30) were randomly divided into three equal groups: I) the treatment group (MLT), where the wounds received leech treatment; II) the positive control group (PC), where the wounds received 1% sodium phenytoin treatment; and III) the negative control group (NC), where the wounds did not receive any treatment. On days 6 and 16, wound biopsy specimens were taken, and prepared sections were stained using various methods. The contraction rate differed significantly (P < 0.05) between the NC group and the other groups. The histopathological evaluation revealed that MLT group showed an accelerated healing process and lower inflammatory response compared to other groups. In ML-treated group maturation and remodeling of collagen had occurred, while in 1% sodium phenytoin treated group, proliferation was the prominent feature. Results showed that the fibroblast was significantly lower in the NC group in comparison to other groups. The number of MNC, s, and PMN, s was significantly higher in the NC group compared to other groups (P < 0.0001). In our study, medicinal leech therapy had a higher success rate in healing for the treatment of excisional wounds in animal models.


The impact of lead on the assimilation efficiency of laboratory-held Diplopoda (Arthropoda) preconditioned in different environmental situations.
In five diplopod species from three families collected from locations with different soil metal contents, the following parameters were examined: the litter mass (and energy) ingested per day, the mass (and energy) assimilation rates, and the litter mass (and energy) assimilated per day, when the diplopods were fed (1) uncontaminated and (2) artificially lead-enriched leaf litter. These parameters were compared between species and between animals from different sites. The mass and energy assimilation efficiencies depend on (1) the size of the species and (2) the collection site of the animals. Relative mass (and in three of the species examined also energy) assimilation was highest in those animals collected from the less contaminated sites. With artificial diets, specimens from a site with soil contaminated by heavy metals showed greater assimilation of both mass and energy than originally unaffected specimens. One species (Glomeris conspersa) was able to compensate for the low assimilation rate by increased consumption, and thus guarantee a sufficient energy supply. One of the other species (Polydesmus denticulatus), however, did not show this compensation. Animals of this species from less contaminated sites showed a very low absolute energy assimilation rate and high mortality under lead treatment.


Viomycin favours the formation of 70S ribosome couples.
The peptide antibiotic viomycin at a concentration of 10 muM inhibits E. coli ribosomes to the extent of about 70% as measured in the poly (U) system, and to about 85% in a natural mRNA (R17) system. Ribosomes from M. smegmatis show no activity at all at this concentration of the antibiotic. Experiments on the Mg+2 dependent dissociation and association of the ribosomal subunits revealed that viomycin stabilizes the 70S couples and promotes association of ribosomal subunits. This response is related to the drug action as indicated by the observation that viomycin resistant strains are not affected by viomycin with respect to dissociation and 70S couple information. A model for the inhibitory action of the drug is proposed.


A micro-scale method for liquid scintillation counting, applicable to radioimmunoassay of steroids and substances of comparable relative molecular mass.
A major expense of radioimmunoassay involving tritiated tracers is that of liquid scintillation counting. We present a micro-scale method that markedly reduces the cost of liquid scintillation counting. The radioimmunoassay is done in 10 X 50 mm tubes. The antibody-bound tracer is precipitated with a second antibody, the precipitate is resuspended in 0.1 ml of water, and 0.3 ml of dioxane is added. One milliliter of a toluene-based scintillation cocktail is added, and the tube is capped and placed in an adapter for liquid scintilation counting. When this method was applied to a double-antibody testosterone radioimmunoassay, it performed comparably to assays counted by the usual method.


Public Health Impact and Cost-Effectiveness of Screening for Active Tuberculosis Disease or Infection Among Children in South Africa.
Although tuberculosis disease is a leading cause of global childhood mortality, there remain major gaps in diagnosis, treatment, and prevention in children because tuberculosis control programs rely predominantly on presentation of symptomatic children or contact tracing. We assessed the public health impact and cost-effectiveness of age-based routine screening and contact tracing in children in South Africa. We used a deterministic mathematical model to evaluate age-based routine screening in 1-year increments from ages 0 to 5 years, with and without contact tracing and preventive treatment. Screening incorporated symptom history and tuberculin skin testing, with chest x-ray and GeneXpert Ultra for confirmatory testing. We projected tuberculosis cases, deaths, disability-adjusted life years (DALYs), and costs (in 2021 U.S. dollars) and evaluated the incremental cost-effectiveness ratios comparing each intervention. Routine screening at age 2 years with contact tracing and preventive treatment averted 11 900 tuberculosis cases (95% confidence interval [CI]: 6160-15 730), 1360 deaths (95% CI: 260-3800), and 40 000 DALYs (95% CI: 13 000-100 000) in the South Africa pediatric population over 1 year compared with the status quo. This combined strategy was cost-effective (incremental cost-effectiveness ratio $9050 per DALY; 95% CI: 2890-22 920) and remained cost-effective above an annual risk of infection of 1.6%. For annual risk of infection between 0.8% and 1.6%, routine screening at age 2 years was the dominant strategy. Routine screening for tuberculosis among young children combined with contact tracing and preventive treatment would have a large public health impact and be cost-effective in preventing pediatric tuberculosis deaths in high-incidence settings such as South Africa.


How to tackle protein structural data from solution and solid state: An integrated approach.
Long-range NMR restraints, such as diamagnetic residual dipolar couplings and paramagnetic data, can be used to determine 3D structures of macromolecules. They are also used to monitor, and potentially to improve, the accuracy of a macromolecular structure in solution by validating or "correcting" a crystal model. Since crystal structures suffer from crystal packing forces they may not be accurate models for the macromolecular structures in solution. However, the presence of real differences should be tested for by simultaneous refinement of the structure using both crystal and solution NMR data. To achieve this, the program REFMAC5 from CCP4 was modified to allow the simultaneous use of X-ray crystallographic and paramagnetic NMR data and/or diamagnetic residual dipolar couplings. Inconsistencies between crystal structures and solution NMR data, if any, may be due either to structural rearrangements occurring on passing from the solution to solid state, or to a greater degree of conformational heterogeneity in solution with respect to the crystal. In the case of multidomain proteins, paramagnetic restraints can provide the correct mutual orientations and positions of domains in solution, as well as information on the conformational variability experienced by the macromolecule.


Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia.
Releasing drug molecules at the targeted location could increase the clinical outcome of a large number of anti-tumor treatments which require low systemic damage and low side effects. Nano-carriers of drugs show great potential for such task due to their capability of accumulating and releasing their payload specifically, at the tumor site. FLT3 inhibitor - gold nanoparticle conjugates were fabricated to serve as vehicles for the delivery of anti-tumor drugs. Lestaurtinib, midostaurin, sorafenib, and quizartinib were selected among the FLT3 inhibitor drugs that are currently used in clinics for the treatment of acute myeloid leukemia. The drugs were loaded onto nanoparticle surface using a conjugation strategy based on hydrophobic-hydrophobic interactions with the Pluronic co-polymer used as nanoparticle surface coating. Optical absorption characterization of the particles in solution showed that FLT3 inhibitor-incorporated gold nanoparticles were uniformly distributed and chemically stable regardless of the drug content. Drug loading study revealed a high drug content in the case of midostaurin drug which also showed increased stability. Drug release test in simulated cancer cell conditions demonstrated more than 56 % release of the entrapped drug, a result that correlates well with the superior cytotoxicity of the nano-conjugates comparatively with the free drug. This is a pioneering study regarding the efficient loading of gold nanoparticles with selected FLT3 inhibitors. In vitro cytotoxicity assessment shows that FLT3-incorporated gold nanoparticles are promising candidates as vehicles for anti-tumor drugs and demonstrate superior therapeutic effect comparatively with the bare drugs.


Dose-dependent reproductive toxicity of sodium benzoate in male rats: Inflammation, oxidative stress and apoptosis.
The synthetic food preservative sodium benzoate (SB) is widely used in both food and pharmaceutical industries. A growing body of evidence highlights the adverse effects of SB on human health; however, effect of the prolonged intake of SB on the reproductive system is not fully elucidated. The current study investigates the effect of different doses of SB (0-1000 mg/kg BW) on the reproductive system of male rats administered oral SB for 90 consecutive days. Results revealed that increasing doses of SB significantly altered the weight of reproductive organs, decreased sperm count and motility and enhanced the percentage of abnormal sperms. This was concomitant with significant decline in plasma testosterone and FSH levels, increase in plasma LH and decrease in the activities of 17β-HSD and 17-KSR enzymes in the testes. Inflammation and oxidative stress were induced as indicated by the significant increase in TNF-α and IL-6 levels, inhibition of antioxidant enzymes activity and levels of GSH, increase in the levels of NO and TBARS and enhanced protein expression of mtTFA and UCP2 in the testes. Interestingly, p53 expression and caspase-3 activity were upregulated in the testes suggesting induction of apoptosis. Histopathological examination of the testes confirmed apoptosis and revealed degenerative alterations of the testes' architecture and perturbation of spermatogenesis. Based upon these findings, the no-observed-adverse-effect level of SB on the reproductive system was determined to be less than 1 mg/kg BW/day, highlighting the risks of long-term exposure to low as well as high doses of SB on male reproductive health.


GABAergic Interneuron and Neurotransmission Are mTOR-Dependently Disturbed in Experimental Focal Cortical Dysplasia.
Focal cortical dysplasia (FCD) is a major cause for drug-resistant epilepsies. The molecular and cellular mechanisms of epileptogenesis in FCD are still poorly understood. Some studies have suggested that deficiencies of γ-aminobutyric acid (GABA) system may play an important role in type II FCD, but it remains controversial. In order to examine whether and how GABAergic interneurons and synaptic function are affected, we generated a somatic mTOR hyperactivation-based mouse model of type II FCD by in utero electroporation, quantified densities of interneurons in the malformed cortices, and recorded miniature inhibitory postsynaptic currents in dysmorphic neurons. We detected 20-25% reduction of GABAergic interneurons within malformed cortices, independent of cortical regions and cell subtypes but proportionate to the decrease of global neuron counts. GABAergic synaptic transmission from interneurons to mTOR hyperactivated dysmorphic neurons was dramatically disrupted, outweighing the decrease of interneuron counts. Postnatal mTOR inhibition partially rescued these alterations of GABAergic system. We also quantified the expression of GABAA receptor, GABA transporter, and chloridion transporter encoding genes and found that their expression was relatively intact within the malformed cortices. Taken together, these results confirmed that GABAergic interneuron and synapse transmission are disturbed profoundly in an mTOR-dependent manner in type II FCD. Our study suggests that postsynaptic mechanisms independent of interneuron reduction or altered expression of GABA synapse genes might be accountable for the impaired GABAergic neurotransmission in type II FCD as well as other mTOR-related epilepsies.


Out-of-hours calls in clinical microbiology: the when, the why and from whom.
Microbiology services provided to hospitals must be delivered 24 h a day. In addition to during routine so-called 'office hours', clinical microbiologists have to provide an on-call service 7 days a week. However, there are few data on what that involves and how the service is delivered. I reviewed the source, reason for, grade of staff from whom the call came and the need for any follow-up, over an 11-year period using a pro-forma, that had been used to review data before this time period. Details were available for 90% of calls received, and data from 809 calls were analysed. The sources of calls were most commonly from medicine specialties [163/809 (20.1%)], neurosurgery (which is a national referral centre) [148/809 (18.3%)] and the intensive care unit [143/809 (17.7%)]. The number of calls received between 23.00 hours and 07.00 hours was 107 (13.2%). Just over half of calls, i.e. 440/809 (54.6%), were related to treatment; 247/809 (30.5%) were for advice on diagnosis; and 79/809 (9.8%) were related to infection prevention and control (IPC) issues. Registrars (a senior training grade) accounted for 492/809 (60.8%) of calls, and 64/809 (7.9%) came from nurses mainly related to IPC matters. Overall, 25.4% (206/809) of calls required follow-up the next day but this increased from 4.5% in 2013 to 67.6% in 2018. The nature of calls received by a clinical microbiologist out-of-hours is varied and may be increasing due to the complexity of case mix and changes in medical staffing. Professional and other organisations would do well to review such workload when deciding on staffing levels and service planning, given increasing public and patient expectations, and the trend towards the centralisation/consolidation of laboratory diagnostic services.


Taurine improves the recovery of neuronal function following cerebral hypoxia: an in vitro study.
Rat hippocampal slices were used in the present study to assess the effect of a pretreatment with the amino acid taurine on their ability to recover synaptic function following a standardized hypoxic insult. After 10 min hypoxia, 47% of all control (untreated) slices exhibited recovery of synaptic function (orthodromically evoked CA1 population spike). Of slices pretreated with 0.5, 1.0 or 2.0 mM taurine, 63, 88 and 97% recovered from the same hypoxic insult. This dose-dependent protective effect was biphasic, as 5.0 mM taurine produced no protection. When hypoxia was extended to 15 min, only 20% of the untreated slices recovered, while 88% of slices treated with 1.0 mM taurine recovered their population spike. The same pretreatment attenuated the fall in the population spike amplitude upon Ca2+ depletion. We hypothesize that taurine plays an important role in an endogenous antihypoxic mechanism through the attenuation of Ca2+ movement across the neuronal membrane.


Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis.
Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 x 10(-4) v 1.4 x 10(-4), Mann-Whitney U, P < .02). The level in CD (4.0 x 10(-4)) was similar to FAP. Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAP. This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.


JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.
Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight.


Effect of aluminum on normal and uremic rats: tissue distribution, vitamin D metabolites, and quantitative bone histology.
The effects of intraperitoneal aluminum chloride (1.5 mg aluminum/kg/day for 9 weeks) were studied in normal and uremic rats. Parameters measured included tissue aluminum, serum vitamin D metabolites, and quantitative bone histology. Aluminum administration increased tissue concentrations of this metal in uremic and nonuremic animals. Bone aluminum concentrations were higher in uremic rats (121 +/- 27 mg/kg compared to 47 +/- 4), whereas liver values were higher in the nonuremic group (175 +/- 47 mg/kg compared to 100 +/- 36). Serum concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were reduced in uremia, but aluminum was without apparent effect on any vitamin D metabolite. Aluminum, in the doses administered, caused no skeletal changes in nonuremic animals. Some uremic, non-aluminum-treated rats developed osteomalacia and marrow fibrosis. However, osteomalacia was more severe and the osteoclast count was higher in the uremic, aluminum-treated rats. In this group of animals the mineral apposition rate was reduced at the metaphyseal endosteum but increased at the periosteum, indicating different control mechanisms at the two sites.


DeepAR: a novel deep learning-based hybrid framework for the interpretable prediction of androgen receptor antagonists.
Drug resistance represents a major obstacle to therapeutic innovations and is a prevalent feature in prostate cancer (PCa). Androgen receptors (ARs) are the hallmark therapeutic target for prostate cancer modulation and AR antagonists have achieved great success. However, rapid emergence of resistance contributing to PCa progression is the ultimate burden of their long-term usage. Hence, the discovery and development of AR antagonists with capability to combat the resistance, remains an avenue for further exploration. Therefore, this study proposes a novel deep learning (DL)-based hybrid framework, named DeepAR, to accurately and rapidly identify AR antagonists by using only the SMILES notation. Specifically, DeepAR is capable of extracting and learning the key information embedded in AR antagonists. Firstly, we established a benchmark dataset by collecting active and inactive compounds against AR from the ChEMBL database. Based on this dataset, we developed and optimized a collection of baseline models by using a comprehensive set of well-known molecular descriptors and machine learning algorithms. Then, these baseline models were utilized for creating probabilistic features. Finally, these probabilistic features were combined and used for the construction of a meta-model based on a one-dimensional convolutional neural network. Experimental results indicated that DeepAR is a more accurate and stable approach for identifying AR antagonists in terms of the independent test dataset, by achieving an accuracy of 0.911 and MCC of 0.823. In addition, our proposed framework is able to provide feature importance information by leveraging a popular computational approach, named SHapley Additive exPlanations (SHAP). In the meanwhile, the characterization and analysis of potential AR antagonist candidates were achieved through the SHAP waterfall plot and molecular docking. The analysis inferred that N-heterocyclic moieties, halogenated substituents, and a cyano functional group were significant determinants of potential AR antagonists. Lastly, we implemented an online web server by using DeepAR (at http://pmlabstack.pythonanywhere.com/DeepAR ). We anticipate that DeepAR could be a useful computational tool for community-wide facilitation of AR candidates from a large number of uncharacterized compounds.


Retracted: The Expression of miR-205 in Prostate Carcinoma and the Relationship with Prognosis in Patients.
[This retracts the article DOI: 10.1155/2022/1784791.].


Nd-YAG laser treatment in preretinal macular fibrosis.
Three eyes with preretinal macular fibrosis (PMF) were treated with the Q-switched Nd-YAG laser. The PMF was idiopathic in two eyes and associated with a vitreous hemorrhage, due to ocular trauma, in the third eye. The three eyes had in common a partial posterior vitreous detachment with vitreous traction on the macula. The Nd-YAG laser beam was focused on the detached posterior hyaloid in front of the macular region. Some holes were made in this membrane or in the adjacent collapsed vitreous cortex. Treatment increased the visual acuity in the three eyes; the vitreous remained partially detached in the two eyes with idiopathic PMF and detached completely in the eye with the secondary PMF. The disentanglement of the fovelar area was revealed by the unfolded appearance of the retinal vessels on fluoangiography.


Laparoscopic sacrocolpopexy posthysterectomy: intraoperative feasibility and safety in obese women compared with women of normal weight.
Our aim was to determine the intraoperative feasibility and complication rate of laparoscopic sacrocolpopexy (LSC) in overweight and obese women compared with women of normal weight. This was a retrospective observational cohort study (Canadian Task Force classification II-2) conducted at a tertiary urogyaenocology unit evaluating 119 women who underwent LSC between March 2005 and January 2013. Body mass index (BMI) was classified as normal (22.89 ± 1.55), overweight (27.12 ± 1.40) and obese (33.47 ± 3.26) according to the World Health Organisation (WHO) classification. There was no difference in intraoperative complication rates for bladder, bowel, ureteric or vascular injury; haemorrhage; conversion to laparotomy; or anaesthetic complications for normal weight, overweight or obese women. Similarly there was no difference in operating time, duration of anaesthetic or hospital stay between BMI class (p = 0.070, p = 0.464, p = 0.898, respectively) postoperative or mesh complication rates. At 6-months' follow-up, there was no difference in Patient Global Impression of Improvement scale (PGI-I) (defined as very much better or much better) between normal weight, overweight and obese women (76.9, 72 and 65.4%, p = .669) or objective cure using the Pelvic Organ Prolapse Quantification (POP-Q) examination (p = 0.402). LSC is feasible, with equivalent intraoperative complication rates for normal weight, overweight and obese women when performed by experienced laparoscopic urogynaecologists. Given the benefits of a laparoscopic approach in obese women, the authors suggest they should be offered LSC as an option to treat vault prolapse when surgical management is being considered.


Purification of alpha-ketoaldehyde dehydrogenase from the human liver and its possible significance in the control of glycation.
Alfa-ketoaldehyde dehydrogenase, which was extracted and purified from human livers, may act on carbonyl compounds, such as 3-deoxyglucosone, and be involved in the control of glycation (Maillard reaction) in the body.


ARE-inducing phenol antioxidant TC-13 improves survival of Drosophila melanogaster in oxidative stress.
The effects of hydrophilic synthetic antioxidant TC-13 sodium (3'-(3'-tert-butyl-4'-hydroxyphenyl)propylthiosulfonate on survival of various strains of Drosophila melanogaster were studied under conditions of oxidative stress induced with H(2)O(2)and paraquat. In a concentration of 1%, TC-13 significantly improved survival of Canton S males treated with H(2)O(2)and in a concentration of 0.2% it improved survival of H(2)O(2)-stressed Oregon R females. The protective effect of the antioxidant under conditions of paraquat-induced stress was observed in Canton S females and Oregon R flies of both genders. Addition of T-13 to diets led to prolongation of the maximum lifespan of insects in the majority of the experiment variants. A relationship between the protective effects of TC-13 and the genotype, gender, and environmental conditions was detected.


Altered dynamics of ubiquitin hybrid proteins during tumor cell apoptosis.
The ubiquitin hybrid genes Uba80 and Uba52 encode ubiquitin (Ub), which is fused to the ribosomal proteins S27a (RPS27a) and L40 (RPL40), respectively. Here, we show that these genes are preferentially over-expressed during hepatoma cell apoptosis. Experiments using the tet-inducible transgenic system revealed that over-expression of the ubiquitin hybrid genes sensitized the cells to apoptosis. Further analysis suggested that Ub, and not RPS27a or RPL40, was associated with apoptotic cell death. Cleavage-resistant mutation analysis revealed that the N-terminal portion and the last two amino acids (GG) of Ub are critical for cleavage at the junction between the two protein moieties. An apoptogenic stimulus enhances the nuclear targeting and aggregation of Ub in the nucleus, resulting in histone H2A deubiquitylation followed by abnormal ubiquitylation of the nuclear envelope and the lamina. These events accompany the apoptotic nuclear morphology in the late stage of apoptosis. Each fused RP is localized in the nucleoli. These results suggest a role for Ub hybrid proteins in the altered nuclear dynamics of Ub during tumor cell apoptosis induced by apoptogenic stimuli.


Differential expression of SNAP-25 isoforms and SNAP-23 in the adrenal gland.
In the rat adrenal gland, we previously observed that SNAP-25 is not restricted to the plasmalemma in noradrenergic cells as it is in adrenergic cells, and hypothesized that SNAP-25 isoform expression is different in the two phenotypes. Expression of SNAP-25 isoforms and SNAP-23 was examined by immunoblotting, immunofluorescence, and RT-PCR. Amplifications of SNAP-25 mRNAs were combined with Southern hybridization, restriction enzyme analysis, and sequencing of cloned PCR products to compare SNAP-25 isoform expression in rat and bovine adrenal glands. SNAP-25 and SNAP-23 mRNA and protein are expressed in the glands; SNAP-23 is enriched in the adrenal cortex, whereas SNAP-25 is restricted to the adrenal medulla. Furthermore, high levels of SNAP-25 and low levels of SNAP-23 are observed in the PC12 cells, whereas both SNAP-25 and SNAP-23 are expressed in adrenal medullary cultures. In all extracts, the SNAP-23 mRNA corresponded to SNAP-23a. SNAP-25a is the major form expressed in rat adrenal glands (75%), as it is in PC12 cells (80%), but both SNAP-25a and SNAP-25b (40% vs. 60%) are expressed in bovine adrenal medulla in situ and in culture. In addition, an enriched population of adrenergic cells (93%) expressed a higher level of SNAP-25b (70%), suggesting that this isoform may not be restricted to fast neurotransmission.


Multi-scale spatial modeling of immune cell distributions enables survival prediction in primary central nervous system lymphoma.
To understand the clinical significance of the tumor microenvironment (TME), it is essential to study the interactions between malignant and non-malignant cells in clinical specimens. Here, we established a computational framework for a multiplex imaging system to comprehensively characterize spatial contexts of the TME at multiple scales, including close and long-distance spatial interactions between cell type pairs. We applied this framework to a total of 1,393 multiplex imaging data newly generated from 88 primary central nervous system lymphomas with complete follow-up data and identified significant prognostic subgroups mainly shaped by the spatial context. A supervised analysis confirmed a significant contribution of spatial context in predicting patient survival. In particular, we found an opposite prognostic value of macrophage infiltration depending on its proximity to specific cell types. Altogether, we provide a comprehensive framework to analyze spatial cellular interaction that can be broadly applied to other technologies and tumor contexts.


Left ventricular function quantified by myocardial strain imaging in small-breed dogs with chronic mitral regurgitation.
The presence of left ventricular (LV) systolic dysfunction may influence prognosis or therapy in dogs with chronic mitral regurgitation (MR). Assessment of LV function in MR by conventional echocardiography is confounded by altered ventricular loading. Myocardial deformation (strain) imaging might offer more sensitive estimates of LV function in this disease. Prospectively measure myocardial strain in dogs with asymptomatic MR compared to a control group. Forty healthy dogs (3.5-11.5 kg): 20 Controls; 20 dogs with MR and LV remodeling (Stage B2), were evaluated in this study. LV size and function were assessed in a short-axis plane. Segmental radial strain and strain rate and global circumferential strain were measured using a 2D echocardiographic speckle-tracking algorithm (GE EchoPAC). Groups were compared using Bonferroni t-tests. Influences of heart rate and body weight were explored with linear regression. The MR group had significantly greater mean values for heart rate, LV size, and LV systolic function. Specifically, LV diastolic diameter, diastole area, shortening fraction, averaged peak systolic and early diastolic radial strain, global circumferential strain, and averaged radial strain rate were significantly greater in the MR group (p < 0.015 to p < 0.001). Strain was unrelated to weight, but weakly correlated with heart rate. Similar to conventional indices, Stage B2 dogs with MR demonstrate hyperdynamic deformation in the short-axis plane. Short-axis strain variables measured by 2D speckle tracking are greater than for controls of similar age and weight. These results imply either preserved LV systolic function or that LV dysfunction is masked by altered ventricular loading.


Atypical haemolytic uraemic syndrome presenting initially as suspected meningococcal disease: a case report.
Haemolytic uraemic syndrome (HUS) is the most common cause of acute renal failure in children and is usually linked with Escherichia coli O157 infection. With a fatality rate of around 5%, some reports have associated antibiotic treatment with a worsening prognosis. We describe a female infant patient, initially treated for suspected meningococcal septicaemia, who went on to develop renal complications and thrombocytopenia characteristic of HUS. A subsequent positive stool sample for E. coli O157 confirmed HUS as an appropriate diagnosis, although there was no evidence of diarrhoea or vomiting throughout the course of her management. The urgency of early recognition and treatment for suspected meningococcal disease in very young children while entirely appropriate can initially divert attention from other serious conditions. Evidence of infection with E. coli O157 infection in this case also highlights what can be a blurred distinction between atypical (non-diarrhoeal) HUS from classical HUS of infective origin.