Management of post-biopsy renal allograft arteriovenous fistulas with selective arterial embolization: immediate and long-term outcomes.
To evaluate the outcomes after transcatheter embolization of percutaneous biopsy-related arteriovenous fistulas in renal allografts. All post-biopsy renal-transplant vascular injuries referred for embolization between June 1999 and October 2006 were reviewed retrospectively. There were six male and six female patients with a mean age of 49.8 years (range 25-67 years); nine patients were symptomatic, three asymptomatic. Colour Doppler ultrasound (CDUS) and angiography showed one intra-renal arteriovenous fistula in 10 patients and two in two patients, combined with a pseudoaneurysm in six patients. Superselective embolization using a single catheter or coaxial microcatheter was performed with 0.035'' coils or 0.018''microcoils, respectively, in all 12 cases. 24-h creatinine clearance values before (the day of biopsy) and after (7-14 days; 3 months) the procedure were compared using the Wilcoxon signed-rank test. Physical examination and CDUS were performed after 1, 6, and 12 months, and yearly thereafter. Mean follow-up was 33.6 months. Complete definitive occlusion of the fistula was achieved consistently with a single procedure. No procedure-related complications occurred. Renal infarction was minor in all patients (0-10% in nine and 10-20% in three). Symptoms resolved completely. Creatinine clearance values obtained before and after embolization were not statistically different (p=0.168;.889 respectively). No late recurrences were reported. Transcatheter embolization with coaxial or single-catheter techniques was effective and safe for treating post-biopsy arteriovenous fistulas in renal transplants. The loss of renal parenchyma was minimal and no mid-term deterioration of allograft function was noted. The long-term survival of the renal allograft seemed to be not affected by embolization.


RNA-Seq reveals placental growth factor regulates the human retinal endothelial cell barrier integrity by transforming growth factor (TGF-β) signaling.
Placental growth factor (PlGF or PGF) is a member of the VEGF (vascular endothelial growth factor) family. It plays a pathological role in inflammation, vascular permeability, and pathological angiogenesis. The molecular signaling by which PlGF mediates its effects in non-proliferative diabetic retinopathy (DR) remains elusive. This study aims to characterize the transcriptome changes of human retinal endothelial cells (HRECs) with the presence and the absence of PlGF signaling. Primary HRECs were treated with the PlGF antibody (ab) to block its activity. The total RNA was isolated and subjected to deep sequencing to quantify the transcripts and their changes in both groups. We performed transcriptome-wide analysis, gene ontology, pathway enrichment, and gene-gene network analyses. The results showed that a total of 3760 genes were significantly differentially expressed and were categorized into cell adhesion molecules, cell junction proteins, chaperone, calcium-binding proteins, and membrane traffic proteins. Functional pathway analyses revealed that the TGF-β pathway, pentose phosphate pathway, and cell adhesion pathway play pivotal roles in the blood-retina barrier and antioxidant defense system. Collectively, the data provide new insights into the molecular mechanisms of PlGF's biological functions in HRECs relevant to DR and diabetic macular edema (DME). The newly identified genes and pathways may act as disease markers and target molecules for therapeutic interventions for the patients with DR and DME refractory to the current anti-VEGF therapy.


Investigation of effects of some immunoadjuvants and routes of antigen administration in raising antibodies in rabbits against metacestode cyst antigens of Taenia multiceps.
The relative efficiency of depot (Freund's complete adjuvant (FCA) and saponin), and non-depot (Corynebacterium parvum strain P. acnes I, C. parvum strain IMI585, and levamisole) immunoadjuvants were compared in raising agglutinating and precipitating antibodies against the metacestode fluid of Taenia multiceps of sheep origin (TMCF). Haemagglutinating but not precipitating antibodies were detectable during the period of primary immunisation. Precipitating antibodies of higher titre were produced for longer when TMCF was injected with immunoadjuvant than when the same volume of TMCF was injected alone. Significantly (P less than 0.05) higher indirect haemagglutination (IHA) titres were produced during the primary response following C. parvum treatment than after FCA treatment. FCA treated rabbits showed significantly (P less than 0.05) higher IHA titres than those receiving C. parvum treatment on day 42 only, during the anamnestic response. Ulcers formed at the sites of injection of depot immunoadjuvants. Significantly (P less than 0.05) higher IHA titres were produced when FCA with TMCF was injected intradermally into 10-12 sites than when the same volume was injected into 4 sites. C. parvum strain IM1585 was a better immunoadjuvant in this system than the strain P. acnes I. The intravenous route of administration yielded better titres than the intraperitoneal route when C. parvum strain P. acnes I was used.


Hypertension in the aging patient. Implications for the selection of drug therapy.
Although earlier debates had questioned the wisdom of treating hypertension in elderly patients, it is now becoming apparent that such treatment is warranted. Systolic hypertension, which prevails in this population, is more closely correlated to hypertensive complications than is diastolic blood pressure. Recent multicenter trials have demonstrated that in this age group, as in younger patients, control of hypertension can significantly decrease the rate of cardiovascular and cerebrovascular events. Many effective antihypertensive agents are available today, but elderly patients, because of their hemodynamic and biochemical characteristics, are particularly vulnerable to the common side effects of most drugs. However, the two newer classes of drugs (the angiotensin-converting enzyme inhibitors and the calcium channel blockers) offer several advantages in terms of favorable hemodynamic and biochemical profiles, convenience of dosing, and maintenance of quality of life. These characteristics justify choosing these agents as first-line therapy for hypertension.


Concurrent infection with bovine leukaemia virus and Theileria annulata in a Friesian calf.
Concurrent infection with bovine leukaemia virus (BLV) and Theileria annulata was diagnosed in a Friesian calf about 6 months of age at a dairy farm at the Qassim region of central Saudi Arabia. The disease ended fatally with signs of liver and heart failure. There was anorexia, pyrexia, anaemia, generalized oedema and jaundice. Haematology showed low RBC counts, PCV percentage and haemoglobin concentration and WBC counts. Lymphocyte differential was high. Examination of blood smears stained with Giemsa's stain showed the presence of piroplasms in red blood cells. Autopsy showed enlarged lymph nodes and lymphosarcoma lesions in the omentum and the heart. There was hydroperitoneum, hydropericardium and hydrothorax. The liver was pale yellow and friable. Impression smears from sliced lymph nodes and stained with Giemsa's stain showed presence of Koch's blue bodies in lymphoblasts. Histopathological examination revealed fatty degeneration of hepatocytes and pleomorphic lymphoblasts and giant cells in lymph nodes. Lymphoblasts infiltrated the omentum and heart tissues. Amyloid was found around blood vessels in the liver, kidneys and lymph nodes. BVL infection was diagnosed by demonstrating antibodies against the virus in serum using agar gel immunodiffusion and was confirmed with ELISA.


Pilot-scale UV/H2O2 advanced oxidation process for municipal reuse water: Assessing micropollutant degradation and estrogenic impacts on goldfish (Carassius auratus L.).
Low concentrations (ng/L-μg/L) of emerging micropollutant contaminants in municipal wastewater treatment plant effluents affect the possibility to reuse these waters. Many of those micropollutants elicit endocrine disrupting effects in aquatic organisms resulting in an alteration of the endocrine system. A potential candidate for tertiary municipal wastewater treatment of these micropollutants is ultraviolet (UV)/hydrogen peroxide (H2O2) as an advanced oxidation process (AOP) which was currently applied to treat the secondary effluent of the Gold Bar Wastewater Treatment Plant (GBWWTP) in Edmonton, AB, Canada. A new approach is presented to predict the fluence-based degradation rate constants (kf') of environmentally occurring micropollutants including carbamazepine [(0.87-1.39) × 10(-3) cm(2)/mJ] and 2,4-Dichlorophenoxyacetic acid (2,4-D) [(0.60-0.91) × 10(-3) cm(2)/mJ for 2,4-D] in a medium pressure (MP) UV/H2O2 system based on a previous bench-scale investigation. Rather than using removal rates, this approach can be used to estimate the performance of the MP UV/H2O2 process for degrading trace contaminants of concern found in municipal wastewater. In addition to the ability to track contaminant removal/degradation, evaluation of the MP UV/H2O2 process was also accomplished by identifying critical ecotoxicological endpoints (i.e., estrogenicity) of the treated wastewater. Using quantitative PCR, mRNA levels of estrogen-responsive (ER) genes ERα1, ERα2, ERβ1, ERβ2 and NPR as well as two aromatase encoding genes (CYP19a and CYP19b) in goldfish (Carassius auratus L.) were measured during exposure to the GBWWTP effluent before and after MP UV/H2O2 treatment (a fluence of 1000 mJ/cm(2) and 20 mg/L of H2O2) in spring, summer and fall. Elevated expression of estrogen-responsive genes in goldfish exposed to UV/H2O2 treated effluent (a 7-day exposure) suggested that the UV/H2O2 process may induce acute estrogenic disruption to goldfish principally because of the possible formation of various oxidation by-products. However, prolonged exposure of goldfish (60 days) in UV/H2O2 treated effluent showed a restoration trend of ER gene expressions, especially in the summer. Collectively, our findings provide valuable indications regarding the long-term in vivo assessment of the MP UV/H2O2 process for removing/degrading endocrine disrupting compounds detected in the municipal wastewater effluents.


The role of oxidation and enzymatic hydrolysis on the in vivo degradation of trimethylene carbonate based photocrosslinkable elastomers.
The in vivo degradation of trimethylene carbonate (TMC) containing elastomers was investigated, and the mechanism of degradation explored through in vitro degradation under enzymatic and oxidative conditions. The elastomers were prepared via UV initiated crosslinking of prepolymers of TMC and equimolar amounts of TMC and epsilon-caprolactone (CL). The degradation process was followed by investigating the changes in the mechanical properties, mass loss, water uptake, sol content, differential scanning calorimetry, and surface chemistry through attenuated total reflectance infrared (ATR-FTIR) spectroscopy. During in vivo degradation, TMC and TMCCL elastomers exhibited surface erosion. The tissue response was of greater intensity in the case of the TMC elastomer. Both elastomers exhibited degradation in cholesterol esterase containing solutions in vitro, but no parallels were found between the rate of in vivo degradation and the rate of in vitro degradation. Only the TMCCL elastomer degraded in lipase. Degradation in a stable superoxide anion in vitro medium was consistent with the observed in vivo degradation results, indicating a dominant role of oxidation through the secretion of this reactive oxygen species by adherent phagocytic cells in the degradation of these elastomers.


Interfacial and emulsifying properties of purified glycyrrhizin and non-purified glycyrrhizin-rich extracts from liquorice root (Glycyrrhiza glabra).
This study compared the interfacial and emulsifying properties of purified saponins and non-purified saponin-rich extracts of Glycyrrhiza glabra, and highlighted potential mechanisms by which crude surface-active compositions, such as liquorice root extract (LRE), act as emulsifiers. LRE presented different fluid properties, in comparison to purified glycyrrhizin (PG), at equivalent glycyrrhizin concentrations. Particularly, it exhibited limited glycyrrhizin fibrilization at pH < pKa and efficiently reduced the interfacial tension at the soybean oil/water interface, independently of pH. LRE also presented better emulsification properties, in comparison to PG samples. Emulsions prepared using LRE had lower droplet sizes when using higher oil mass fractions or lower homogenization pressures, which was attributed to 2 main factors: (i) efficient adsorption of glycyrrhizin molecules at relatively low interfacial curvatures, thus accelerating oil phase breakup during homogenization and (ii) sufficient coverage of newly generated droplets due to adsorption of residual surface-active components (e.g. proteins), thus minimizing droplet coalescence.


Successful placement of a pyeloamniotic shunt catheter for ureteropelvic junctional obstruction in utero.
A fetus with severe left ureteropelvic junctional obstruction was managed by the insertion of a left pyeloamniotic shunt catheter at 28 weeks' gestation. An otherwise healthy baby boy was delivered seven weeks later. The place of fetal surgical techniques for obstructive uropathies is discussed.


[Recovery time after general anesthesia with propofol administered in continuous infusion or with isoflurane].
The recovery time after Propofol-Tiva (P) or Isoflurane-anesthesia (I) for elective plastic surgery was studied by the Authors in two series of patients: 60 in group P, 60 in group I. All patients received a standard premedication and induction-anesthesia (premedication: Atropine 0.005 mg/kg i.m.; induction: Fentanyl 2.1 micrograms/kg+Propofol 2.5 mg/kg i.m. and Succinylcholine 1 mg/kg i.v. for tracheal intubation) and a different maintenance (group P received an infusion of 12 mg/kg/h for 10 min, 9 mg/kg/h for the next 10 min and 6 mg/kg/h thereafter+Fentanyl 1.4 micrograms/kg/h, group I clinically appropriate inspired concentration of Isoflurane and both Fentanyl-bolus at demand). They were ventilated mechanically with air and oxygen mixture (FiO2 = 0.3) to maintain normal blood-oxygen tension and normocarbia. The results showed that the recovery time was significantly shorter in the group P than in the group I and that Propofol-Tiva is accompanied by a more rapid recovery than Isoflurane-anesthesia.


Loss of function of retinoic acid in liver leads to steatohepatitis and liver tumor: A NASH animal model.
To explore the role of retinoic acid (RA) in liver, we developed transgenic mice expressing retinoic acid receptor alpha dominant negative form (RARE) in hepatocytes using by albumin promoter and enhancer. At 4 months of age, the RARE transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes including VLCAD, LCAD and HCD were down-regulated. On the other hand, peroxisomal beta-oxidation and its related enzymes including AOX and BFE were up-regulated. Expression of CYP4a10, CYP4a12 and CYP4a14 was increased, suggesting that omega-oxidation of fatty acids in microsome was accelerated. In addition, formation of H(2)O(2) and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed liver tumors which are hepatocellular carcinoma or adenoma. The incidence of tumor formation was increased with age. Expression of beta-catenin and cyclin D1 was enhanced, and TCF-4/beta-catenin complex was increased whereas RARalpha/beta-catenin complex was decreased. Feeding on high RA diet reversed histological and biochemical abnormalities, and inhibited occurrence of liver tumor. Taken together, hepatic loss of RA function leads to development of steatohepatitis and liver tumor and RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.


TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway.
Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) can cause brain injury, which is one of the factors affecting the recovery of brain function in CA patients. There is increasing evidence that tumor necrosis factor-like weak apoptosis-inducing factor (TWEAK) is associated with the brain injury diseases. This study was aimed to investigate the modulation mechanism of TWEAK involved in brain injury after cardiac arrest/subsequent cardiopulmonary resuscitation (CA/CPR). For in vivo experiments, healthy male Sprague-Dawley (SD) rats were applied to establish CA/CPR model, and oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated neurons model was established in vitro. TWEAK short hairpin RNAs (shRNAs) were injected into the lateral ventricle of CA/CPR rats or transfected into OGD/R cell culture to analyze the consequent alteration in neurological scores, behavioral tests, cell proliferation, cell apoptosis, and neuroinflammation through immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA). There were high expressions of TWEAK and fibroblast growth factor-inducible 14 (Fn14) in the cerebral cortex of CA/CPR rats and OGD/R-stimulated neuronal cells. TWEAK knockdown attenuated cell apoptosis, inflammation and showed better behavioral tests in CA/CPR rats. Furthermore, TWEAK shRNAs obviously facilitated cell proliferation, suppressed apoptosis and inflammation after OGD/R injury. Western blotting results stated that TWEAK silencing promoted phosphorylated p38 (p-p38) and phosphorylated p65 (p-p65) expressions. TWEAK might be involved in the pathogenesis of CA/CPR through inhibiting p38 MAPK/NF-κB pathway.


The value of observation as adjunct to the objective-subjective examination.
A new approach is presented to the refractive procedure by adding observation, both surreptitious and direct, as an adjunct, an aid and a supplement to differential diagnosis in a refractive examination and in visual analysis.


Sodium-dependence of sustained force in potassium contracture of cat ventricle.
Following exposure to low-Na solutuion, the initial phase of K-contracture in cat ventricle is prominent while the second (sustained) phase is markedly attenuated. Monensin, a Na-specific ionophore, enhances the second phase of K-contracture following exposure to low-Na solution.


Burnout, resilience and work engagement among Dutch intensivists in the aftermath of the COVID-19 crisis: A nationwide survey.
The COVID-19 crisis put a strain on intensive care resources everywhere in the world increasing the risk of burnout. Previously, the prevalence of burnout among Dutch intensivists was found to be low. Engagement and resilience among intensivists have not previously been studied quantitatively, however, both are related to burnout and provide a possible way to mitigate burnout. Our objective was to study burnout and its association with work engagement and resilience among Dutch intensivists in the aftermath of the COVID-19 crisis. An online questionnaire was sent to all Dutch intensivists. The questionnaire consisted of questions on personal and work-related characteristics and validated questionnaires: the Maslach Burnout Inventory, the Utrecht Work Engagement Scale, and the Resilience Evaluation Scale. The response rate was 27.2% with 162 evaluable responses. Thirteen respondents (8.0%) were classified as having burnout, 63 (38.9%) respondents were reporting high work engagement. Burnout was found to be negatively associated with both work engagement and resilience. In the aftermath of the 2020 COVID-19 crisis, we found a raised prevalence of burnout among intensivists, however this is still low in international comparisons. Intensivists with burnout scored low on resilience and low on work engagement.


Comparison of Maternal and Umbilical Cord Blood Selenium Levels in Low and Normal Birth Weight Neonates.
To compare the maternal and umbilical cord serum selenium concentrations in Low and normal birth weight neonates. A case-control study was carried out in Vali-Asr and Akbarabadi Hospitals (Jan. to Dec. 2013). Two groups; case group; 91 mothers who delivered a low birth weight (LBW) neonate and control group; 86 subjects who delivered a normal birth weight neonate were selected. Immediately after birth, 5 ml of maternal blood and umbilical cord blood were collected, and sent to laboratory to assay Se concentrations. To compare both groups' blood Se concentration, data were analyzed in SPSS 16.0. Eighty six (48.6%) mothers with normal birth weight neonates and 91 (51.4%) mothers with low birth weight infants entered the study. Mean maternal mothers' age and mean maternal blood Se were 28.55 + 5.90 years and 79.3756+26.46915. A significant association was seen between maternal blood and cord blood Se level in control and case group (P value < 0.0001, r = 0.69) and (P value<0.001, r = 0.79). On the other hand no differences were seen between 2 groups' maternal blood Se level (P Value = 0.65). Umbilical Cord blood Se concentration was not also different between case and control group (P value = 0.46). We found that maternal and umbilical cord blood Se concentrations were not different in low and adequate birth weight infants, however; umbilical cord Se concentrations were positively correlated with maternal blood Se concentrations.


Analysis of meso-2,3-dimercaptosuccinic acid in human urine by capillary electrophoresis using direct injection.
meso-2,3-Dimercaptosuccinic acid ( meso-DMSA) is an effective chelating agent for the treatment of lead poisoning. We have developed a capillary electrophoresis (CE) method to monitor the urinary excretion of meso-DMSA in human beings. The urine sample was directly injected for analysis in CE without the requirement of solid-phase extraction (SPE). The meso-DMSA was detected in 20 mM borate buffer (pH 8.3) using a 60-cm length bare fused-silica capillary (75-microm ID, 52.5-cm effective length). The meso-DMSA can be extensively biotransformed during metabolism, and no meso-DMSA in urine samples was found in our studies. Any metabolized meso-DMSA can be successfully converted to free meso-DMSA by chemical reduction with dithiothreitol (DTT). In addition, samples were also treated with ethylenediaminetetraacetic acid (EDTA) to transchelate any meso-DMSA that is coordinated with metal ions present in the urine samples. The total amount of meso-DMSA present as these chemical forms was quantified after chemical reduction and addition of EDTA. The detection limit of meso-DMSA was about 50 microM, the RSD of peak area and migration time of meso-DMSA were 4-8% and less than 1%, respectively.


Actions on gamma-motoneurones elicited by electrical stimulation of group III muscle afferent fibres in the hind limb of the cat.
The reflex actions evoked by electrical stimulation of group III muscle afferent fibres were investigated with micro-electrode recordings from ninety-three gamma-motoneurones projecting to hind-limb muscles of cats anaesthetized with chloralose. For seventy-eight of the ninety-three gamma-cells the frequency of occurrence and types of effects mediated via group II and group III muscle fibres were compared. Seventy-seven of the cells tested at intensities which excited group III and seventy-five of the cells tested at intensities which excited both group II and group III afferent fibres were classified as either static or dynamic, using the method of mesencephalic stimulation (Appelberg, 1981). The responsiveness of the whole sample of gamma-motoneurones to inputs from group III muscle fibres was high and comparable to that found with group II fibres. It was found that group III muscle fibres acted preferentially on static gamma-motoneurones. In contrast, group II fibres acted preferentially on dynamic gamma-motoneurones. Both excitatory and inhibitory effects were provoked by stimulation of group III fibres. Generally excitation was more frequent than inhibition. A strong dominance of excitation over inhibition was found in flexor muscles, and a weaker prevalence of excitation was also encountered in extensor muscles. This prevalence of excitation in extensor gamma-motoneurones is in contrast to the striking predominance of group III-evoked inhibition of extensor alpha-motoneurones as described by the flexion reflex afferents concept. A comparative survey is also given of the patterns of responses elicited in individual posterior biceps-semitendinosus and gastrocnemius-soleus gamma-cells by stimulation of group II and group III fibres. These data further corroborate the view that reflexes from high-threshold muscle afferent fibres to gamma-motoneurones are organized differently from those to alpha-motoneurones. The functional implications of these findings are discussed. It is proposed that the pools of gamma-motoneurones should be considered as integrative systems intercalated between descending and reflex pathways on the one hand and the skeletomotor neurones on the other. The descending messages and the multisensory peripheral information, integrated in the fusimotor neurones, undergo final adjustment in the muscle spindle. The link to the skeletomotor neurones is formed by the primary spindle afferents. These constitute a final common input, conveying integrated detailed polymodal feed-back, to the central nervous system. This new concept is referred to as the 'final common input' hypothesis.


Improving Managers' Psychophysical Well-Being: Effectiveness of Respiratory Sinus Arrhythmia Biofeedback.
High work stress has been consistently associated with disturbed autonomic balance, specifically, lowered vagal cardiac control and increased sympathetic activity, which may lead to increased cardiovascular risk. Stress management procedures have been proposed to reduce autonomic dysfunctions related to work stress in different categories of workers exposed to heightened work demands, while a limited number of studies addressed this issue in managers. The present study was aimed at evaluating the effectiveness of a respiratory sinus arrhythmia (RSA) biofeedback (BF) intervention on psychological and physiological outcomes, in managers with high-level work responsibilities. Thirty-one managers leading outstanding private or public companies were randomly assigned to either a RSA-BF training (RSA-BF; N = 16) or a control group (N = 15). The RSA-BF training consisted of five weekly 45 min sessions, designed to increase RSA, whereas controls had to provide a daily stress diary once a week. After the training, managers in both groups reported reduced heart rate at rest, lower anxiety levels and improvement in health-related quality of life. More importantly, managers in the RSA-BF group showed increased vagal control (as indexed by increased RSA), decreased sympathetic arousal (as indexed by reduced skin conductance and systolic blood pressure) and lower emotional interferences, compared to managers in the control group. Results from this study showed that RSA-BF training was effective in improving cardiac autonomic balance at rest. Moreover, findings from this study underline the effectiveness of biofeedback in reducing psychophysiological negative outcomes associated with stress in managers.


Bothrops leucurus venom induces acute hypotension in rats by means of its phospholipase A2 (blD-PLA2).
Cardiovascular effects induced by snake venoms, in spite of having a crucial role in the outcome of the envenomation, have been less studied than other toxic activities displayed by these venoms. In this study we evaluated acute cardiovascular responses to Bothrops leucurus venom - Bl-V - both in vivo, in anesthetized rats, and in vitro, in isolated rat mesenteric resistance arteries. Bl-V (10-100 μg protein/kg) caused dose-dependent hypotension, followed by gradual recovery (2-20 min) to basal levels, and induced dose-dependent (1-20 μg/mL) vasodilation in pre-contracted arteries, what was more pronounced when the endothelium remained intact. These effects were partially counteracted by pre-treatment with indomethacin (cyclooxygenase inhibitor). Prior incubation of Bl-V with commercial pentavalent Bothrops antivenom also attenuated the cardiovascular effects induced by the venom, in spite of it not being among the venoms used for the development of the bothropic antivenom. Through an approach based on two chromatographic steps and mass spectrometry (MALDI-ToF and MALDI-ISD), a component with acute cardiovascular effects was isolated and identified as the basic phospholipase blD-PLA2, previously purified from the venom of B. leucurus. Taken together, our results show that, at low doses, the venom of B. leucurus induces transient, acute hypotension in anesthetized rats following systemic vasodilation in a dose-dependent way. In addition, we provide clear evidence of the involvement of the enzymatic activity of blD-PLA2 in this cardiovascular response, acting via the production of vasodilating prostanoids.


Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types.
SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes. This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model. This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.


[Upper gastrointestinal (UGI) endoscopy in Louga (Senegal): patients' profile and difficulties encountered].
This study aimed to determine the epidemiological, clinical and endoscopic profile of patients referred for upper gastrointestinal (UGI) endoscopy to the Clinique Magou in Louga and to analyze the difficulties encountered. We conducted a retrospective and descriptive study by analysing the reports of 248 gastrointestinal endoscopies performed between 1st January and 31st December 2014. The average age was 39.9 years, with a sex ratio of 2.3 in favor of females. The majority of patients (56.5%) came from a rural area. Patients were mostly housewives (55.2%). The majority of prescribers were physicians (77.8%). Epigastralgia was the main indication. Hiatal hernia dominated (33.1%), followed by normal examinations (22.5%) and isolated gastroesophageal reflux disease (12.5%). Only 2 results out of 13 biopsies performed were reported. No requested endoscopic control was performed. Few upper gastrointestinal (UGI) endoscopies are performed in Louga. The typical patients' profile is constituted by young housewives living in rural areas, complaining of gastralgies. Their endoscopic examination, instead of being normal, show hiatal hernia or gastroesophageal reflux disease. The difficulties are related to non-received anatomopathological results and to the absence of endoscopic control after treatment.


A case of Norman-Roberts syndrome identified from postnatal diagnosis of microlissencephaly.
Lissencephaly is a rare brain malformation. What differentiates microlissencephaly from classical lissencephaly and other variants is the presence of severe microcephaly. Very few postnatal cases of Norman-Roberts syndrome are described in the literature. We report a case of microlissencephaly with a polymalformative syndrome that prompted postnatal diagnosis of Norman-Roberts syndrome.


Information-seeking behavior in complementary and alternative medicine (CAM): an online survey of faculty at a health sciences campus.
The amount of reliable information available for complementary and alternative medicine (CAM) is limited, and few authoritative resources are available. The objective is to investigate the information-seeking behavior of health professionals seeking CAM information. Data were gathered using a Web-based questionnaire made available to health sciences faculty affiliated with the University of California, San Francisco. The areas of greatest interest were herbal medicine (67%), relaxation exercises (53%), and acupuncture (52%). About half the respondents perceived their CAM searches as being only partially successful. Eighty-two percent rated MEDLINE as a useful resource, 46% personal contacts with colleagues, 46% the Web, 40% journals, and 20% textbooks. Books and databases most frequently cited as useful had information about herbs. The largest group of respondents was in internal medicine (26%), though 15% identified their specialties as psychiatry, psychology, behavioral medicine, or addiction medicine. There was no correlation between specialty and patterns of information-seeking behavior. Sixty-six percent expressed an interest in learning more about CAM resources. Health professionals are frequently unable to locate the CAM information they need, and the majority have little knowledge of existing CAM resources, relying instead on MEDLINE. Medical librarians need to educate health professionals in the identification and use of authoritative CAM resources.


Bonding and curing considerations for incipient and hidden caries.
Contemporary adhesive systems and restorative composite materials can successfully seal and restore teeth and can facilitate the use of a minimally invasive cavity preparation technique. These systems give the operator the potential to reinforce damaged teeth and preserve healthy tooth structure. The adhesion principles rely on strict adherence to excellence in clinical technique. Differences in clinical results may depend may more on the operator's adherence to good clinical technique than the specific material selected.


Primary mediastinal large B cell lymphoma with coexisting aberrations of C-MYC and BCL-2: a case report and literature review.
Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive lymphoma characteristic with distinct clinical, morphologic, and immunophenotypic features. The rearrangements of C-MYC, BCL2 and/or BCL6 which are common in diffuse large B-cell lymphoma (DLBCL) are typically absent in PLMBCL. Here we proved a novel case of PMLBCL with concurrent rearrangements of C-MYC and BCL2. Histology showed typical pathomorphological features of PLMBCL. Fluorescent in situ hybridization (FISH) studies showed rearrangements of C-MYC and copy number variation (CNV) of BCL2 gene. It is not well known on the clinical significance of rearrangements of C-MYC and BCL2 genes in PMLBCL. The case gives evidence that cytogenetic testing is necessary for PMLBCLs to get precise clinical evaluation and appropriate treatment.


The influence of hyperosmolality on heart function.
Hyperosmolality produces a reduction in myocardial water content, an increase in ventricular stiffness and coronary blood flow, and decrease in ventricular performance. The alterations of myocardial dehydration and ventricular stiffness are more pronounced in glucose-induced, and those of ventricular performance in urea-induced hyperosmolality.


Collegial Activity Learning between Heterogeneous Sensors.
Activity recognition algorithms have matured and become more ubiquitous in recent years. However, these algorithms are typically customized for a particular sensor platform. In this paper we introduce PECO, a Personalized activity ECOsystem, that transfers learned activity information seamlessly between sensor platforms in real time so that any available sensor can continue to track activities without requiring its own extensive labeled training data. We introduce a multi-view transfer learning algorithm that facilitates this information handoff between sensor platforms and provide theoretical performance bounds for the algorithm. In addition, we empirically evaluate PECO using datasets that utilize heterogeneous sensor platforms to perform activity recognition. These results indicate that not only can activity recognition algorithms transfer important information to new sensor platforms, but any number of platforms can work together as colleagues to boost performance.


Deliberating clinical research with cognitively impaired older people and their relatives: an ethical add-on study to the protocol "Effects of Temporary Discontinuation of Antihypertensive Treatment in the Elderly (DANTE) with Cognitive Impairment".
To explore the decision-making process involving elderly subjects with mild cognitive impairment and a relative when asked to participate in a clinical trial. In this qualitative study, we investigated the decision-making process during the informed consent conversations between the researchers of a clinical trial and 18 persons aged 75 years and older, with a Mini-Mental State Examination score ≥21 and ≤27. This assessment was performed by both observation and a standardized interview with the older person and a close relative who could act as a proxy (surrogate) decision maker, if necessary. The informed consent conversation and procedure took place at the home of the potential participants. Videotapes or audiotapes were transcribed and analyzed by using coding schemes. The participants were able to formulate substantial reasons why they would want to participate in the clinical trial. Willingness to help others and contribute to medical knowledge, combined with the absence of substantial risks, were predominant reasons for participation. Most older subjects did consult their relatives, who generally considered them capable of deciding for themselves. Notwithstanding their (mild) cognitive impairment, these older subjects were able to formulate substantiated reasons for participation in a clinical trial. Thus, it is plausible that they were capable of making this decision themselves, which was affirmed by their relatives. Recognition of the desire to contribute unselfishly to research that might benefit others has important implications for future clinical research conducted in older people with mild cognitive impairment.


Contraceptive and hormonal properties of the stem bark of Dysoxylum binectariferum in rat and docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction.
This study was aimed to investigate the pregnancy interceptive activity of the stem bark of Dysoxylum binectariferum Hook. f. administered during the pre- and peri-implantation periods and immediately after implantation by oral route in adult female Sprague-Dawley rats. Ethanolic extract and its fractions were administered to female rats on Days 1-10, Days 1-7, Days 1-5 or Day 1 postcoitum by oral route. At autopsy on Day 12, the number and status of corpora lutea and implantations were recorded. For estrogenic activity, ovariectomized immature rats received the test extract or the vehicle once daily for 3 days and at autopsy on Day 4, uterine weight and status of vaginal opening and extent of vaginal cornification were recorded. For antiestrogenic activity, the extract was administered along with ethinyl estradiol. Docking analysis of rohitukine, the alkaloid isolated from active chloroform soluble fraction, to estrogen receptor (ERalpha) was conducted using AutoDock 3.0.5 on a Linux workstation. The ethanolic extract intercepted pregnancy in rats at a daily dose of 500 mg/kg on Days 1-7 postcoitum. On fractionation, the activity was localized in the chloroform fraction, which inhibited pregnancy in all females at the 35-mg/kg dose on Days 1-7, at the 50-mg/kg dose on Days 1-5 or at the single 300-mg/kg dose on Day 1 postcoitum. Chromatography of this fraction yielded an alkaloid, rohitukine, which prevented pregnancy at the 10-mg/kg dose administered on Days 1-7 but was partially (45%) effective at this dose when administered during the entire preimplantation period and ineffective even at 10 times this dose when administered only on Day 1 postcoitum, except that there was a significant reduction in implantation number in pregnant females. While the active chloroform soluble fraction was devoid of any estrogen agonistic or antagonistic properties, a mild uterotropic effect without induction of premature opening of vagina or cornification of vaginal epithelium was observed in rohitukine at the 10-mg/kg dose. Rohitukine, with an almost similar molecular size (mol. wt. 305) as 17beta-estradiol, fits ideally into the hydrophobic pocket of ER. While it does not appear to simultaneously interact with GLU353, ARG394 and HIS524 as estradiol to elicit frank estrogenic response, different conformations of the ligand or its metabolite(s) might acquire geometry with phenolic groups at C-3', C-5 and C-7 positions disposed in a fashion to interact with active site(s) of ER, which might be responsible for its contraceptive and/or weak uterotropic effects. The absence of a basic side chain directed toward the antiestrogen binding site (ASP351) on the receptor appears to be responsible for the lack of any estrogen antagonistic activity. Findings demonstrate the antifertility activity of the ethanolic extract of D. binectariferum, its chloroform soluble fraction and rohitukine. Efforts are being made to enhance the anti-implantation activity of rohitukine by structural modifications.


Studies on the localization of 5-hydroxytryptamine and its receptors in human placenta.
The localization of 5-hydroxytryptamine (5-HT) and its receptors in human placenta was studied under light and electron microscopy using immunohistochemistry and in situ hybridization. The syncytiotrophoblast, cytotrophoblast, stromal cells and decidual cells in human placentae all appeared to be 5-HT immunoreactive. The 5-HT immunoreactive material was distributed in cytoplasm with negative nuclei. The 5-HT immunoreactive material was also found in capillary endothelium. Trophoblast cells cultured in serum-free medium also showed 5-HT immunoreactivity in the cytoplasm. Fetal white blood cells and both syncytiotrophoblast and cytotrophoblast in human placenta showed 5-HT receptor immunoreactivity and 5-HT1A receptor mRNA hybridized signal was also detected in cytoplasm. The stromal cells and capillary endothelium in placental villi and maternal decidual cells all showed 5-HT receptor immunoreactivity in cytoplasm. The small flattened vesicles and large dense cored vesicles within trophoblast cells showed electron-dense 5-HT receptor immunoreactivity using immunoelectron microscopy. These results suggest that human placenta may not only produce 5-HT but also be a 5-HT target organ, and that 5-HT may not only play roles in placental development and pregnancy maintenance by paracrine and autocrine interactions but may also take part in regulating fetal development.


Effects of microRNA-338 Transfection into Sciatic Nerve on Rats with Experimental Autoimmune Neuritis.
Nerve demyelination or axonal lesions are characteristic of experimental autoimmune neuritis (EAN). Previous studies have demonstrated that microRNA-338 can regulate the differentiation and maturation of oligodendrocytes and Schwann cells and promote injured peripheral nerves in rats. In this study, we used microRNA-338 coded lentivirus vector (miR-338-LV) in a Lewis rat EAN model, in with the conjunction P0 peptide 180-199 which was injected into the footpads of animals to induce immunization. The clinical scores of miR-338-LV and intravenous immunoglobulin (IVIg) (positive drug) groups were significantly superior to those of untreated group at disease peak and disease plateau (p < 0.05). The nerve conduction velocity and the compound nerve action potential amplitude of miR-338-LV and IVIg groups increased significantly compared to those of the untreated group at disease peak (p < 0.01). At disease peak, myelin swelling, cavity formation, and lamellae separation showed improvement in miR-338-LV and IVIg groups compared to untreated group. S100 and NF200 expression in miR-338-LV and IVIg groups increased compared to that in untreated group. Iba1 and S100 co-expression in Schwann cells in miR-338-LV and IVIg groups decreased compared to that in untreated group, which was indicative of the reduced conversion of Schwann cells into inflammatory cells. Overall, miR-338-LV in sciatic nerves might improve neuromuscular function in EAN by inhibiting the conversion of Schwann cells into inflammatory cells.


Behavioural arousal and its habituation in the squirrel fish, Holocentrus rufus: the role of the telecephalon.
Squirrel fish were captured, maintained for 2 days and then tested for their responses to stimuli in laboratory aquaria. A tap on the side of the aquarium or a shadow moving overhead elicited an arousal response involving a reduction in opercular movements, movement of the pectoral fins, and erection of the spiny dorsal fin. This latter response, when regularly provoked by a moving shadow at 15-s intervals, decreased in duration and habituated. When fish were restricted in a wire mesh trough and the stimulus was the onset of illumination to one eye at 15-s intervals, responses were quantitatively similar although shorter in duration. A series of stimuli delivered to one eye until habituation followed by a series to the other eye reduced the duration of initial responses and the number of trials for habituation of responses to stimuli delivered to the second eye. Responses were equivalent regardless of which eye (left or right) was first presented with stimuli. Section of the telencephalic anterior commissure considerably restricted the transfer of information about experience of stimuli presented to the first eye. Commissural section, combined with unilateral lesions in the posterior-medial telencephalon, severely impaired habituation of responses to the contralateral eye. Lateral lesions had no effect. The results are discussed in relation to the visual projection in Holocentrus and telecephalic involvement in arousal and its habituation in teleosts as a whole.


Emerging Machine Learning Techniques for Modelling Cellular Complex Systems in Alzheimer's Disease.
We live in the big data era in the biomedical field, where machine learning has a very important contribution to the interpretation of complex biological processes and diseases, since it has the potential to create predictive models from multidimensional data sets. Part of the application of machine learning in biomedical science is to study and model complex cellular systems such as biological networks. In this context, the study of complex diseases, such as Alzheimer's diseases (AD), benefits from established methodologies of network science and machine learning as they offer algorithmic tools and techniques that can address the limitations and challenges of modeling and studying cellular AD-related networks. In this paper we analyze the opportunities and challenges at the intersection of machine learning and network biology and whether this can affect the biological interpretation and clarification of diseases. Specifically, we focus on GRN techniques which through omics data and the use of machine learning techniques can construct a network that captures all the information at the molecular level for the disease under study. We record the emerging machine learning techniques that are focus on ensemble tree-based techniques in the area of classification and regression. Their potential for unraveling the complexity of model cellular systems in complex diseases, such as AD, offers the opportunity for novel machine learning methodologies to decipher the mechanisms of the various AD processes.


1,3,5-Tri-fluoro-2,4,6-tri-iodo-benzene-piperazine (2/1).
The single-crystal structure of the title compound, C4H10N2·2C6F3I3, features a moderately strong halogen bond between one of the three crystallographically distinct iodine atoms and the nitro-gen atom. The iodine-nitro-gen distance is 2.820 (3) Å, corresponding to 80% of the sum of their van der Waals radii. The C-I⋯N halogen bond angle is 178.0 (1)°, consistent with the linear inter-action of nitro-gen via a σ-hole opposite the carbon-iodine covalent bond. The other two iodine atoms do not engage in halogen bonding. Some weak C-H⋯F and -H⋯I interactions are also observed. The complete piperazine molecule is generated by symmetry.


Advancement in COVID-19 detection using nanomaterial-based biosensors.
Coronavirus disease 2019 (COVID-19) pandemic has exemplified how viral growth and transmission are a significant threat to global biosecurity. The early detection and treatment of viral infections is the top priority to prevent fresh waves and control the pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified through several conventional molecular methodologies that are time-consuming and require high-skill labor, apparatus, and biochemical reagents but have a low detection accuracy. These bottlenecks hamper conventional methods from resolving the COVID-19 emergency. However, interdisciplinary advances in nanomaterials and biotechnology, such as nanomaterials-based biosensors, have opened new avenues for rapid and ultrasensitive detection of pathogens in the field of healthcare. Many updated nanomaterials-based biosensors, namely electrochemical, field-effect transistor, plasmonic, and colorimetric biosensors, employ nucleic acid and antigen-antibody interactions for SARS-CoV-2 detection in a highly efficient, reliable, sensitive, and rapid manner. This systematic review summarizes the mechanisms and characteristics of nanomaterials-based biosensors for SARS-CoV-2 detection. Moreover, continuing challenges and emerging trends in biosensor development are also discussed.


After the Women's Health Initiative: decision making and trust of women taking hormone therapy.
To describe decision making and trust of women who were on hormone therapy (estrogen and progestin or estrogen alone) when the Women's Health Initiative findings were initially released July 9, 2002. Telephone surveys of 204 patients randomly selected from a large academic primary care practice (66% response rate) were conducted from July to September 2003. Women age 50 years and older who were taking hormone therapy on July 9, 2002, were included. The survey assessed: prevalence of discontinuing hormone therapy; knowledge of and reactions to the Women's Health Initiative; trust in medical recommendations; and future prevention behavior. Of 204 women, their mean age was 61 years, 70% were white, 56% were college educated, and 54% were taking both estrogen and progestin. Most (94%) had heard of the Women's Health Initiative and the majority (70%) stopped hormone therapy. Being nonwhite (adjusted RR 1.37, 95% CI [1.16-1.48]) and having taken estrogen and progestin (1.37, [1.18-1.49]) were significantly associated with stopping hormone therapy. Among women who had heard of the Women's Health Initiative (n = 191), 26% reported losing trust in medical recommendations generally and 34% were less willing than before the Women's Health Initiative to take new drugs to prevent heart disease. Nonwhites were less willing than whites to take new drugs for heart disease prevention (aRR 1.58 [1.02-2.18]). Most women discontinued hormone therapy after the Women's Health Initiative results were published. Given their experience with hormone therapy, some women, particularly nonwhites, are now less trusting of medical recommendations and less likely to take drugs for cardiovascular disease prevention.


Ethanol decreases cytosolic-free calcium ions in vascular smooth muscle cells as assessed by digital image analysis.
Effects of ethanol on intracellular-free Ca2+ concentration in cultured rat aortic smooth muscle cells were examined by digital imaging fluorescence microscopy using the Ca2+ fluorescence indicator, fura-2. Ethanol induced dose-dependent decrements in cytosolic-free Ca2+ concentration at 45 mM and 90 mM, which was consistent with previously reported observations of relaxation in intact rat aortic tissues. However, ethanol at high pharmacological concentrations (e.g., 450 mM) failed to induce any further inhibition in cytosolic-free Ca2+ concentration. Our results suggest that the vasodilator effects of ethanol, observed on intact blood vessels, may result in part from an interference with the availability of Ca2+ for excitation-contraction coupling in vascular smooth muscle cells.


Precocious axons and improved survival of rat hippocampal neurons on lysine-alanine polymer substrates.
We tested the hypothesis that other polymers of lysine would be better substrates for culture of CNS neurons than polylysine itself. In a serum-free medium optimized for survival of hippocampal neurons grown on substrates of poly-D-lysine, 13% more neurons survived on substrates to which a sequential copolymer of lysine and alanine (LAS) was applied (P = 0.006). The effect was specific for the sequential polymer, in contrast to the random copolymer of lysine and alanine. This suggests that average cationic charge density is not as important as the spacing of these charges. More dramatically, immunostaining for the axon-associated microtubule-associated protein, tau, indicated a 2-fold higher rate of fiber growth on LAS. The somatodendritic cytoskeletal component MAP2 also appeared to be increased in cells cultured on LAS. This suggests that cytoskeletal differentiation in general and axon formation in particular are stimulated by the LAS substrate. Scanning electron microscopy supported this conclusion. By circular dichroism, the conformation of LAS in phosphate-buffered saline appeared to be a random coil, indistinguishable from poly-D-lysine. These results indicate that LAS is a superior substrate to polylysine for growth of CNS neurons. LAS may be useful for regeneration of damaged circuits in the CNS as well as a substrate for connections to a neuroprosthesis.


[The characteristics of the clinical course in individual types of radiation-induced cataracts].
Twenty-eight patients exposed to acute and chronic ionizing radiation were followed up. Radiation cataracts were diagnosed in 22 eyes. Localizations of changes in the lens after ionizing and solar radiation are similar. Opacities are localized under the posterior lenticular capsule, round the nucleus, and under the anterior capsule and do not depend on the type of radiation. Opacities caused by solar radiation are notably smaller and look as numerous small dots. Study of cataracts of different origin and assessment of the efficacies of different anticataract drugs were carried out for evaluating the progress of different types of cataracts (cellular, extracellular, and capsular forms).


Human circadian rhythm studies: Practical guidelines for inclusion/exclusion criteria and protocol.
As interest in circadian rhythms and their effects continues to grow, there is an increasing need to perform circadian studies in humans. Although the constant routine is the gold standard for these studies, there are advantages to performing more naturalistic studies. Here, a review of protocols for such studies is provided along with sample inclusion and exclusion criteria. Sleep routines, drug use, shift work, and menstrual cycle are addressed as screening considerations. Regarding protocol, best practices for measuring melatonin, including light settings, posture, exercise, and dietary habits are described. The inclusion/exclusion recommendations and protocol guidelines are intended to reduce confounding variables in studies that do not involve the constant routine. Given practical limitations, a range of recommendations is provided from stringent to lenient. The scientific rationale behind these recommendations is discussed. However, where the science is equivocal, recommendations are based on empirical decisions made in previous studies. While not all of the recommendations listed may be practical in all research settings and with limited potential participants, the goal is to allow investigators to make well informed decisions about their screening procedures and protocol techniques and to improve rigor and reproducibility, in line with the objectives of the National Institutes of Health.


The first transplantation of the lung in a human revisited.
The first homotransplantation of the lung in a human was performed in early 1963, thirty years ago. It is the purpose of this review to evaluate the significance of this event and to determine its effects on the further development of lung transplantation.


In vitro and in vivo activities of sparfloxacin, other quinolones, and tetracyclines against Chlamydia trachomatis.
Sparfloxacin was more potent than other quinolones (tosufloxacin, lomefloxacin, ciprofloxacin, ofloxacin, fleroxacin, enoxacin, and norfloxacin) and as potent as minocycline and doxycycline in activity against Chlamydia trachomatis in vitro and in vivo. Sparfloxacin was more bactericidal than minocycline against C. trachomatis D/UW-3/Cx.


Oral health-related quality of life in patients with disc displacement with reduction after counselling treatment versus counselling associated with jaw exercises.
The aim of this study was to compare the effectiveness of two types of treatment (counselling programme versus counselling programme plus jaw exercises) to improve the quality of life of patients with disc displacement with reduction (DDWR). Patients were divided into two groups. The test group received guidelines for temporomandibular disorders (TMD) plus jaw exercises for DDWR, and the control group received only guidelines for TMD. The total number of investigated patients was 70, thus 35 per group. The oral health-related quality of life was assessed by the OHIP-14 questionnaire. Both groups were evaluated at the baseline and 30 days post-treatment. In the counselling group, there was statistically significant decrease in pain (P = .015) and social disability (P = .046) subscales. In the counselling plus jaw exercise group, there was statistically significant decrease in all subscales (P < .05). At 30 days follow-up, there was a statically significant difference between the two groups in pain (P = .004), psychological discomfort (P < .001), psychological disability (P < .001) and social disability (P = .029) subscales. The counselling programme plus jaw exercise protocol showed greater improvement in oral health-related quality of life than the group performing only the counselling programme in patients with DDWR.


Synthesis of rat apolipoprotein E by Escherichia coli infected with recombinant bacteriophage.
A cDNA library was constructed from rat liver polyadenylated RNA using the expression vector lambda gt11-Amp3. Several clones expressing antigenic determinants for rat apolipoprotein E were identified. The cDNA insert in one clone was further characterized and found to have a sufficient length (1120 base pairs) to code for full length apolipoprotein E. Restriction mapping and nucleotide sequencing showed the clone to contain the coding region for apolipoprotein E flanked by about 120 nucleotides at the 3'-side and by about 64 nucleotides on the 5'-side. One of the proteins produced by the clone was found to be a prokaryotic/eukaryotic hybrid protein reacting with antibodies to both bacterial beta-galactosidase and rat apolipoprotein E.


Phloroglucinol-meroterpenoids from the leaves of Eucalyptus camaldulensis Dehnh.
Fourteen undescribed phloroglucinol-meroterpenoids, namely eucalypcamals A-N, were isolated from a CH2Cl2 extract of the leaves of Eucalyptus camaldulensis Dehnh. In addition, from the same extract, twelve known phloroglucinols, three known flavonoids, and four known phenolic compounds were also isolated. The structures of the undescribed compounds were analyzed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and high resolution electrospray ionization mass spectrometry (HRESIMS). The assignments of the absolute configurations were performed by comparing the experimental electronic circular dichroism (ECD) data with the calculated values. Eucalyprobusal E was found to be cytotoxic against HCT116, Jurkat, and MDA-MB-231 cell lines with IC50 values of 17.6, 9.44, and 17.9 μM, respectively. Eucalrobusone F exhibited antibacterial activity against methicillin-resistant S. aureus (MRSA) and S. aureus with minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values of 4/4 μg/mL while euglobal Ia1 showed antifungal activity with MIC/MFC values of 16/16 μg/mL.


Transfection of human mutated K-ras in mouse NIH-3T3 cells is associated with increased cloning efficiency and DNA aneuploidization.
The aim of the study was to test the hypothesis that a human mutated K-ras protein induces abnormalities in mitosis and development of sub-clones characterized by changes in DNA ploidy and proliferation. For this purpose, we used control and NIH-3T3 mouse cells transfected with the human codon 12 G-C-mutated K-ras oncogene. We found that abnormal mitoses, mainly characterized by lagging chromosomes in prometaphase or anaphase, had a significantly higher frequency in transfected cells than in control cells. The generation of sub-clones was screened by limiting-dilution experiments followed by cell expansion. Cloning efficiency was much higher for the K-ras transfected cells with 858/2112 (41%) successful sub-clones than for control, which provided 564/2592 (22%) sub-clones. DNA flow cytometry of 4.6-diamidino-2-phenilindole-2-hydrochloride-stained nuclei from randomly selected sub-clones was performed in order to evaluate DNA index and S-phase fraction values. We found 9 out of 100 DNA aneuploid sub-clones generated by the K-ras-transfected cells vs. 1 out of 100 for the controls. Overall, our data indicate that high expression of the mutationally activated human K-ras product in NIH-3T3 cells was associated with abnormal mitoses, increase of cloning efficiency and DNA aneuploidization.


Dysphagia screening in residential care settings: A scoping review.
Older adults with dysphagia are at a higher risk of experiencing serious complications where dysphagia is not identified and adequately managed. Nursing personnel are critical for timely identification and management of dysphagia and prevention of these subsequent serious complications in residential care settings. To identify dysphagia screening tools used in residential care and to establish whether validated and used as per guidelines, their diagnostic accuracy and reliability and to identify the prevalence rate of dysphagia in this setting. A scoping review based on Arksey & O'Malley (2005) methodological framework. An electronic search of databases CINAHL, Pubmed and Scopus was conducted. Reference lists were checked in all identified articles for additional studies. Peer-reviewed publications describing the process of identifying dysphagia and using a screening protocol in residential care settings were considered for inclusion. All identified studies were screened by reading of titles, keywords and abstracts. Those articles that were deemed eligible for inclusion were read in full. Nineteen quantitative studies and one mixed-methods study out of 1,674 articles were included in the review. Thirteen different instruments for dysphagia screening were identified, with the Modified Water Swallow Test being the most commonly used. Other diagnostic procedures, such as fiberoptic endoscopic evaluation of swallowing, pulse oximetry or cervical auscultation, were implemented along with the administration of a dysphagia screening tool in six studies. The 3-Ounce Water Swallow Test, the Yale Swallow Protocol and the Gugging Swallowing Screen were identified as the instruments with the best clinical accuracy values. The reported prevalence of dysphagia in this setting ranged from 15% to 70%. Formal dysphagia screening in residential care settings is not common practice. The dysphagia screening tools identified in this review are not validated for use in this setting. The implementation of dysphagia screening protocols specific to this population may facilitate identification of dysphagia and avoid complications.


[Dose-effect correlations in a stochastic function of cell reactivity].
A random reactivity function involving a correlation between "refusal" probabilities in cells irradiated with various doses was estimated. The dose-effect curves were obtained for this reactivity function and their behaviour in the simplest correlation functions was analyzed.


Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells.
The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2-5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.


Enhanced secretion of endothelin-1 by elevated glucose levels from cultured bovine aortic endothelial cells.
We have investigated the effect of glucose on the release of endothelin-1-like immunoreactivity (ET-1-LI) from cultured bovine aortic endothelial cells. Elevation of glucose concentrations in cultured media from 5.5 to 11.1 or 22.2 mM significantly stimulated ET-1-LI release from cultured endothelial cells. An aldose reductase inhibitor did not affect the high glucose-induced ET-1-LI release. These findings suggest the possibility that hyperglycemia in diabetic patients enhances ET-1-LI release at the local site of vascular endothelium, which might be involved in the developments of vascular complications and atherosclerosis.


Protective role of adiponectin against testicular impairment in high-fat diet/streptozotocin-induced type 2 diabetic mice.
Type 2 diabetes (T2D) is the most common endocrine and metabolic disorder, leading to reproductive impairments and infertility in male. Our recent study showed crucial role of adiponectin in the regulation of testicular functions, and the circulating level of adiponectin declines in diabetes. The current study thus aimed to examine the efficacy of adiponectin in improving testicular dysfunction in high-fat diet/streptozotocin-induced T2D mice. T2D was induced in pre-pubertal mice fed with high-fat diet for ∼10 weeks followed by a single dose of streptozotocin. T2D mice showed presence of increased body mass, hyperglycemia, hyperinsulinemia, insulin resistance, increased oxidative stress, and declined serum testosterone compared to vehicle-treated control mice. The spermatogenic, steroidogenic, metabolic, and antioxidative parameters were evaluated in T2D mice treated with adiponectin for both two and four weeks. The exogenous administration of adiponectin to T2D mice showed enhanced serum testosterone and expression of testicular steroidogenic markers proteins, insulin receptor and GLUT8 proteins, increase in intra-testicular concentrations of glucose and lactate and activity of LDH and antioxidant enzymes compared to the levels in untreated T2D mice. This suggests that treatment of adiponectin effectively improves testicular functions by increasing expression of insulin receptor-mediated increased transport of energy substrate (glucose and lactate) and a marked reduction in oxidative stress are the possible mechanism by which adiponectin effectively improves testicular function in T2D mice.


Effects of human elastase on von Willebrand factor in highly purified factor VIII concentrate and in cryoprecipitate.
The susceptibility of v. Willebrand factor (vWF) and F.VIII in virus-inactivated factor VIII/vWF concentrate (Behring-Haemate-HS (BHS] and in cryoprecipitate (Behring-Ristofact) to digestion by highly purified, cathepsin G free human neutrophil elastase (HNE) was compared. In Haemate-HS HNE induced a degradation of the vWF subunit. This reaction was dependent on time and enzyme concentration. It resulted in disappearance of large size vWF multimers, an anodal shift of vWF peak in crossed immunoelectrophoresis and a decrease of F.VIII:C and Ristocetin cofactor activities. In contrast in cryoprecipitate even high HNE concentration did not provoke changes of these parameters. Both Haemate-HS and Ristofact were free of alpha 1-proteinase inhibitor (alpha 1 PI) and alpha 2-macroglobulin (alpha 2 M) but they differed in the content of other contaminating proteins. In particular Haemate-HS was fibrinogen-free but Ristofact contained 6.6 mg/ml. Purified fibrinogen added to Haemate-HS was found highly effective in protecting vWF in Haemate-HS against the proteolytic degradation and loss of activity under the influence of HNE.


Neocortical projections of the suprageniculate and posterior thalamic nuclei in the marsupial brush-tailed possum, Trichosurus vulpecula (Phalangeridae), with a comparative commentary on the organization of the posterior thalamus in marsupial and placental mammals.
Axonal transport methods were used to determine the extent and organisation of neocortical projections from the suprageniculate (SG) and posterior (PO) thalamic nuclei in the brush-tailed possum. Our findings show that SG projects extensively to the auditory cortex, overlapping the cortical projection field of the medial geniculate nucleus, and to the immediately neighbouring association cortex. Though the input relationships of SG appear similar to those reported for other mammals, placental and marsupial, a strong SG projection to auditory cortex has not been reported previously. Neocortical relationships of PO are characterised by an orderly point-to-point projection to all but the most rostral parts of the motor-somaesthetic cortex. There is also a substantial projection to the entire posterior parietal association cortex. The PO-neocortex projection is reciprocally organised. The PO-neocortical projection in the possum is similar to that reported in the Virginia opossum, rat, and several other mammals. There is a major difference in organisation in comparison with certain monkeys where the PO projection is much more restricted and does not involve the motor and somaesthetic cortex. We conclude that PO is similarly organised in many, though not all, mammals, including the marsupials, rodents, insectivores, and prosimian primates. The possum SG, on the other hand, is clearly distinct from other mammals in its extensive projection to auditory cortex, though we cannot say at present whether this a general property of marsupial mammals or a peculiarity restricted to this species and possibly its close relatives.


The shared biomarkers and pathways of systemic lupus erythematosus and metabolic syndrome analyzed by bioinformatics combining machine learning algorithm and single-cell sequencing analysis.
Systemic lupus erythematosus (SLE) is one of the most prevalent systemic autoimmune diseases, and metabolic syndrome (MetS) is the most common metabolic disorder that contains hypertension, dyslipidemia, and obesity. Despite clinical evidence suggested potential associations between SLE and MetS, the underlying pathogenesis is yet unclear. The microarray data sets of SLE and MetS were obtained from the Gene Expression Omnibus (GEO) database. To identify the shared genes between SLE and MetS, the Differentially Expressed Genes (DEGs) analysis and the weighted gene co-expression network analysis (WGCNA) were conducted. Then, the GO and KEGG analyses were performed, and the protein-protein interaction (PPI) network was constructed. Next, Random Forest and LASSO algorithms were used to screen shared hub genes, and a diagnostic model was built using the machine learning technique XG-Boost. Subsequently, CIBERSORT and GSVA were used to estimate the correlation between shared hub genes and immune infiltration as well as metabolic pathways. Finally, the significant hub genes were verified using single-cell RNA sequencing (scRNA-seq) data. Using limma and WGCNA, we identified 153 shared feature genes, which were enriched in immune- and metabolic-related pathways. Further, 20 shared hub genes were screened and successfully used to build a prognostic model. Those shared hub genes were associated with immunological and metabolic processes in peripheral blood. The scRNA-seq results verified that TNFSF13B and OAS1, possessing the highest diagnostic efficacy, were mainly expressed by monocytes. Additionally, they showed positive correlations with the pathways for the metabolism of xenobiotics and cholesterol, both of which were proven to be active in this comorbidity, and shown to be concentrated in monocytes. This study identified shared hub genes and constructed an effective diagnostic model in SLE and MetS. TNFSF13B and OAS1 had a positive correlation with cholesterol and xenobiotic metabolism. Both of these two biomarkers and metabolic pathways were potentially linked to monocytes, which provides novel insights into the pathogenesis and combined therapy of SLE comorbidity with MetS.


[Effect of 6N2'O-dibutyryl adenosine-3',5'-cyclomonophosphate on the protein synthesis of the subpharyngeal ganglia complex in the mollusk, Helix pomatia].
Proteins of the Helix pomatia abdominal complex were separated by electrophoresis. The electrophoretic mobility of most of the proteins was RF = 0.2--0.6. The abdominal ganglion was incubated in the medium with 1 = (4.5H3)-leucine and 2.10(-6) M 6N2'O-dibutyryladenosine-3',5'-cyclomonophosphate for 3, 6 and 24 hours. It was shown that radioactivity of specific low-mol wt neuronal proteins was increased by the former, but the latter inhibited this process.


Fates of metal radiotracers added to a whole lake: accumulation in slimy sculpin (Cottus cognatus) and white sucker (Catostomus commersoni).
Six gamma-emitting isotopes, iron-59, cobalt-60, zinc-65, selenium-75, cesium-134 and mercury-203, were added in mid-summer to Lake 224 of the Experimental Lakes Area in northwestern Ontario, Canada. Isotope activities in whole bodies of slimy sculpins and in blood, gills, gut contents, kidney, liver and spleen of white suckers were determined for periods up to 247 days after isotope addition. Results demonstrate delay between contamination of a lake and transfer of contaminant to these fish species. General relationships between movement and distribution of isotopes in water and their accumulation in these fish indicate that direct accumulation from water is not a major route of uptake.


Balloon catheter dilatation of renal artery stenosis in the dog. A preliminary report.
Renal artery stenosis was successfully created in 2 out 3 dogs using a nonsurgical, percutaneous and intra-arterial technique. In both instances, it was possible to reduce the stenosis by dilatation with a balloon catheter. The possible clinical implications of this technique are briefly discussed.


Effectiveness of training in increasing awareness about managing pressure injuries in emergency departments.
Emergency room conditions and the characteristics of the patients followed up pose a risk for pressure injury. This study was conducted as a pilot study to assess the effectiveness of a training program in increasing the awareness of healthcare professionals working in an emergency department about how to manage pressure injuries. The study was a prospective, pre-test post-test intervention study without a control group. The study included 595 patients who were hospitalized in the emergency room for more than two hours and voluntarily agreed to participate, as well as 11 physicians and 17 nurses working in the emergency department between 15 April and 19 June 2019 2019. It was carried out in three stages. In the first stage, the 30-day pressure injury incidence rate in the emergency department was evaluated using the "Emergency Department Patients Information and Pressure Injury Assessment Form" and "The Braden Scale for Predicting Pressure Injury Risk". In the second stage, the healthcare professionals were given training about pressure injuries. The knowledge levels of healthcare professionals before and after the training were evaluated using "The Descriptive Characteristics Form for Emergency Department Personnel (doctors and nurses)" and "The Questionnaire for Identifying and Preventing Pressure Injury". In the third stage, the 30-day pressure injury incidence rate in the was re-evaluated after the training using the same two scales as before. The SPSS 25 package program was used to evaluate the data in terms of frequency, percentage, mean and standard deviation, and the Mann-Whitney U Test for independent groups, the t-test, the correlated sample t-test, the Wilcoxon Signed Rank test, Pearson Chi-square test, Yates Chi-square test and Fisher's Exact Chi-square test were also used. The mean knowledge test score of the healthcare professionals working in the emergency department was determined as X¯±SD = 53.71 ± 14.70 before the training and X¯±SD = 58.57 ± 11.83 after the training. The average score on the prevention dimension of the Questionnaire for Identifying and Preventing Pressure Injury was found to be statistically significantly higher than before the training (p < 0.05). The pressure injury incidence in the emergency department was 12.5% before the training and 8.8% afterwards. It was observed that the knowledge of healthcare professionals about pressure injury was insufficient and that training given on this topic both increased their knowledge and decreased the incidence of pressure injury. However, the difference was not statistically significant. Training about pressure injuries is important for preventing pressure injury, identifying the injury early, treating the injury appropriately and increasing the awareness of healthcare professionals.


Corrigendum: The utilization of psychiatric and psychotherapeutic services in Germany - individual determinants and regional differences.
[This corrects the article on p. 3-22 in vol. 2.].


Synthesis of dendritic silver nanostructures supported by graphene nanosheets and its application for highly sensitive detection of diazepam.
In this paper, preparation, characterization and application of a new sensor for fast and simple determination of trace amount of diazepam were described. This sensor is based on Ag nanodendrimers (AgNDs) supported by graphene nanosheets modified glassy carbon electrode (GNs/GCE). The AgNDs were directly electrodeposited on the surface of electrode via potentiostatic method without using any templates, surfactants, or stabilizers. The structure of the synthesized AgNDs/GNs was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis, X-ray diffraction (XRD) and electrochemical impedance spectroscopy (EIS) techniques. The nanodendrimers with tree-like and hierarchical structures have a fascinating structure for fabrication of effective electrocatalysts. The experimental results confirmed that AgNDs/GNs/GC electrode has good electrocatalytic activity toward the reduction of diazepam. A low detection limit of 8.56×10(-8)M and a wide linear detection range of 1.0×10(-7) to 1.0×10(-6)M and 1.0×10(-6) to 20×10(-6)M were achieved via differential pulse voltammetry (DPV). The proposed electrode displayed excellent repeatability and long-term stability and it was satisfactorily used for determination of diazepam in real samples (commercially tablet, injection and human blood plasma) with high recovery.


Characteristics of induced ventricular fibrillation cycle length in symptomatic Brugada syndrome patients.
Limited information is available on the ventricular fibrillation (VF) spectrum in Brugada syndrome (BS) patients. We clarified differences in the VF cycle length (CL) using fast-Fourier transformation (FFT) analysis in symptomatic and asymptomatic BS patients. VF was induced by pacing from the right ventricular (RV) apex and/or RV outflow tract (RVOT) for >8s. A 4096-point FFT analysis of results from 28 male BS patients (51.1 ± 13.7 years old) was performed. Dominant frequency (DF) from phases 1 (4s) to 6 was obtained at 2-s intervals. The average DF from surface and intracardiac electrograms (ECG: DF(ECG); ICE: DF(ICE,), respectively) was compared between symptomatic and asymptomatic patients. Symptomatic patients had a significantly shorter effective refractory period at a CL of 600 ms at the RVOT than asymptomatic patients. DF(ECG) significantly increased with phase (5.64 ± 0.32 Hz in phase 1 to 6.16 ± 0.52 Hz in phase 6) and was significantly higher in symptomatic patients than in asymptomatic patients. DF(ICE) had the same characteristics as DF(ECG). Induced VF in BS patients can be characterized using FFT analysis. Our data support the hypothesis that symptomatic patients have a significantly shorter VF CL than asymptomatic patients.


Thermodynamics in [Mn(II)-antibiotics-bacitracin] mixed system: a polarographic approach.
Polarographic technique was used to determine the kinetic parameters, thermodynamic parameters and stability constants (log(beta)) of Mn(II) complexes with neomycin, chlortetracycline, oxytetracycline, tetracycline, penicillin V and penicillin G as primary ligands and bacitracin as the secondary ligand, at pH 7.3+/-0.01 and an ionic strength mu=1.0 M (NaClO(4)) at 25 degrees C. The study was also carried out at 35 degrees C to determine the stability constants and thermodynamic parameters viz. enthalpy change (DeltaH), entropy change (DeltaS) and free energy change (DeltaG) of complexes.


Leiomyosarcoma of the inferior vena cava.
Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignancy. Approximately 350 cases of this disease are known worldwide. Surgical treatment of this condition remains an extremely difficult task. In this case report, we present an experience of successful radical treatment of a leiomyosarcoma of the suprarenal IVC without vascular reconstruction. The patient was treated with resection of the suprarenal portion of the IVC with the tumor; however, in view of adequate blood outflow from the right lobe of the liver, prosthetic replacement of the IVC with right hepatic vein reimplantation was not performed.


Targets for Intervention? Preoperative Predictors of Postoperative Ileus After Colorectal Surgery in an Enhanced Recovery Protocol.
Postoperative ileus occurs in up to 30% of colorectal surgery patients and is associated with increased length of stay, costs, and morbidity. While Enhanced Recovery Protocols seek to accelerate postoperative recovery, data on modifiable preoperative factors associated with postoperative ileus in this setting are limited. We aimed to identify preoperative predictors of postoperative ileus following colorectal surgery in Enhanced Recovery Protocols, to determine new intervention targets. We performed a retrospective single-center cohort study of patients ≥ 18 years old who underwent colorectal surgery via Enhanced Recovery Protocols (7/2015-7/2017). Postoperative ileus was defined as nasogastric tube insertion postoperatively or nil-per-os by postoperative day 4. Preoperative risk factors including comorbidities and medication use were identified using multivariable stepwise logistic regression. Of 530 patients, 14.9% developed postoperative ileus. On univariate analysis of perioperative and postoperative factors, postoperative ileus patients had increased psychiatric illness, antidepressant and antipsychotic use, American Society of Anesthesiologists classification, ileostomy creation, postoperative opioid use, complications, surgery duration, and length of stay (p < 0.05). Multivariable logistic regression model for preoperative factors identified psychiatric illness, preoperative antipsychotic use, and American Society of Anesthesiologists classification ≥ 3 as significant predictors of postoperative ileus (p < 0.05). Postoperative ileus remains a common complication following colorectal surgery under Enhanced Recovery Protocols. Patients with pre-existing psychiatric comorbidities and preoperative antipsychotic use may be a previously overlooked cohort at increased risk for postoperative ileus. Additional research and preoperative interventions within Enhanced Recovery Protocols to reduce postoperative ileus for this higher-risk population are needed.


Cucurmosin induces the apoptosis of human pancreatic cancer CFPAC-1 cells by inactivating the PDGFR-β signalling pathway.
Pancreatic cancer treatment is limited and effective drugs are needed. We investigated cucurmosin (CUS)-induced apoptosis in cystic fibrosis pancreatic adenocarcinoma cells (CFPAC-1) and a possible mechanism of action to evaluate the clinical application potential of this new Type I ribosome-inactivating protein. We analyzed the growth inhibition and apoptosis of CFPAC-1 cells via methylthiazol tetrazolium assay and fluorescence-activated cell sorting. Western blot was used to analyze the protein levels of caspase 3, bcl-2, caspase 9, platelet-derived growth factor receptor (PDGFR)-β, PI3K, Akt, p-Akt, the mammalian target of rapamycin (mTOR), p-mTOR, P70S6K-α, p-P70S6K-α, 4E-BP1, p-4E-BP1 and p-Bad after CUS intervention. The mRNA expression of PDGFR-β was analyzed using reverse transcription polymerase chain reaction. CUS inhibited the proliferation of pancreatic cancer cells. The induction of apoptosis depended on the CUS dose and incubation time. The drug inhibited all of the examined proteins in the PI3K/Akt/mTOR signalling pathway and induced the active fragments of caspase 3 and caspase 9. CUS downregulated PDGFR-β expression but no significant change was observed at the mRNA level. CUS strongly inhibits the growth of CFPAC-1 by inducing cell apoptosis. CUS downregulated the expression of PDGFR-β at the protein level and induced the apoptosis of CFPAC-1 through the PI3K/Akt/mTOR signalling pathway.


Anaesthesia and cystic fibrosis.
Cystic fibrosis occurs in 1 in 2000 children and the majority now reach adulthood. The disease is a complex multisystem disorder which is likely to challenge anaesthetists with increasing frequency. In this review the presentation and genetics of the disease are briefly described, followed by a detailed account of the pathophysiology relevant to anaesthesia. The pre-operative assessment and conduct of anaesthesia are discussed and some suggestions made regarding management.


Characteristics of patients with spinal tuberculosis: seven-year experience of a teaching hospital in Southwest China.
The purpose of this study was to investigate the characteristics of patients managed for spinal tuberculosis at the orthopaedics department of a teaching hospital in Chongqing, China, between 2004 and 2010. The study used a retrospective chart review. The epidemiology, clinical features, laboratory test results, imaging study findings, and treatment methods were recorded. The annual incidence of spinal tuberculosis was stable throughout the study period. There were 284 patients, 147 women and 137 men, with a mean age of 38.2 years. The majority of the lesions involved the thoracic spine (45.3%), followed by the lumbar spine (45.0%). Multiple level skip lesions were seen in 5.6% of cases. The erythrocyte sedimentation rate was normal in 26.8% of patients. The C-reactive protein (CRP) was normal in 30.2% of patients. Type A and type O were the most common blood types. Neurological involvement was seen in 21.8% of patients. Concomitant tuberculosis of the lung was seen in 73 (25.7%). The patients with middle school education and above account for 60.4% (102/169) in rural patients and 68.7% (79/115) in urban patients. Mean time from symptom onset to diagnosis was 18.0 months (range, three days to 360 months), and there was a significant difference between the rural patients (23.0 months) and the urban patients (10.7 months) (p=0.001, t=-3.300). Surgical treatment was performed in 233 patients (82.0%). The preferred surgical procedure was radical anterior debridement, bone grafting and internal fixation (132 patients, 46.5%). There were 13 patients (4.2%) with anti-tuberculous chemotherapy drug allergy or toxicity, streptomycin anaphylaxis and toxicity in 12, and isoniazide anaphylaxis and toxicity in one. No mortality was related to spinal TB. The annual incidence of spinal tuberculosis remained unchanged throughout the study period and most of the patients did not pay much attention to the disease and received timely treatment. Thus, we should strengthen the census and treatment of spinal tuberculosis in Southwest China.


ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin.
The human insulin gene enhancer-binding protein islet-1 (ISL1) is a transcription factor involved in the differentiation of the neuroendocrine pancreatic cells. Recent studies identified ISL1 as a marker for pancreatic well-differentiated neuroendocrine neoplasms. However, little is known about ISL1 expression in pancreatic poorly differentiated and in extrapancreatic well and poorly differentiated neuroendocrine neoplasms. We studied the immunohistochemical expression of ISL1 in 124 neuroendocrine neoplasms. Among pancreatic neuroendocrine neoplasms, 12/13 with poor differentiation were negative, whereas 5/7 with good differentiation but a Ki67 >20% were positive. In extrapancreatic neuroendocrine neoplasms, strong positivity was found in Merkel cell carcinomas (25/25), pulmonary small cell neuroendocrine carcinomas (21/23), medullary thyroid carcinomas (9/9), paragangliomas/pheochromocytomas (6/6), adrenal neuroblastomas (8/8) and head and neck neuroendocrine carcinomas (4/5), whereas no or only weak staining was recorded in pulmonary carcinoids (3/15), olfactory neuroblastomas (1/4) and basaloid head and neck squamous cell carcinomas (0/15). ISL1 stained the neuroendocrine carcinoma component of 5/8 composite carcinomas and also normal neuroendocrine cells in the thyroid, adrenal medulla, stomach and colorectum. Poorly differentiated neuroendocrine neoplasms, regardless of their ISL1 expression, were usually TP53 positive. Our results show the almost ubiquitous expression of ISL1 in extrapancreatic poorly differentiated neuroendocrine neoplasms and neuroblastic malignancies and its common loss in pancreatic poorly differentiated neuroendocrine neoplasms. These findings modify the role of ISL1 as a marker for pancreatic neuroendocrine neoplasms and suggest that ISL1 has a broader involvement in differentiation and growth of neuroendocrine neoplasms than has so far been assumed.


Child and Adolescent Suicide Attempts, Suicidal Behavior, and Adverse Childhood Experiences in South Africa: A Prospective Study.
This is the first known prospective study of child suicidal behavior in sub-Saharan Africa. Aims were to determine whether (1) cumulative exposure to adverse childhood experiences (ACEs) predicts later suicidality and (2) heightened risks are mediated by mental health disorder and drug/alcohol misuse. Longitudinal repeated interviews were conducted 1 year apart (97% retention) with 3,515 adolescents aged 10-18 years in South Africa (56% female; <2.5% refusal). Random selection of census enumeration areas from urban/rural sites within two provinces and door-to-door sampling included all homes with a resident adolescent. Measures included past-month suicide attempts, planning, and ideation, mental health disorders, drug/alcohol use, and ACE, for example, parental death by AIDS or homicide, abuse, and exposure to community violence. Analyses included multivariate logistic regression and multiple mediation tests. Past-month suicidality rates were 3.2% of adolescents attempting, 5.8% planning, and 7.2% reporting ideation. After controlling for baseline suicidality and sociodemographics, a strong, graded relationship was shown between cumulative ACE and all suicide behaviors 1 year later. Baseline mental health, but not drug/alcohol misuse, mediated relationships between ACE and subsequent suicidality. Suicide attempts rose from 1.9% among adolescents with no ACE to 6.3% among adolescents with >5 ACEs (cumulative odds ratio [OR], 2.46; confidence interval [CI], 1.00-6.05); for suicide planning, from 2.4% to 12.5% (cumulative OR, 4.40; CI, 2.08-9.29); and for suicide ideation, from 4.2% to 15.6% (cumulative OR, 2.99; CI, 1.68-5.53). Preventing and mitigating childhood adversities have the potential to reduce suicidality. Among adolescents already exposed to adversities, effective mental health services may buffer against future suicidality.


Screening of novel inhibitors targeting lactate dehydrogenase A via four molecular docking strategies and dynamics simulations.
Lactate dehydrogenase A (LDHA) is a metabolic enzyme which catalyzes the interconversion of lactate and pyruvate in the glycolysis pathway, thus playing key roles in aerobic glycolysis. The inhibition of LDHA by small molecules has become an attractive strategy for anticancer therapy in recent years. However, very few LDHA inhibitors have been reported, even though a great deal of effort has directed into identifying LDHA inhibitors using structure-based approaches. Therefore, high-throughput and high-accuracy screening approaches are still urgently needed in order to target LDHA effectively. In the present work, after establishing that our docking strategies performed well using test datasets, we screened 32791 Specs products for their docking scores with the substrate-binding pocket and, separately, the cofactor-binding pocket of LDHA. We subsequently identified 76 hits (i.e., ligands that show low docking scores) for the cofactor-binding pocket and 27 hits for the substrate-binding pocket. Two representative compounds, ZINC20036549 and ZINC19369718, were then chosen for further MD simulation analysis, and we found that these compounds maintained their inhibitory activity during the MD simulations. Meanwhile, we found that ZINC19369718 interacts with a novel binding site close to the active site, and that this interaction may inhibit the catalytic activity of LDHA. Together, these results offer not only a new paradigm for identifying Specs drug-like products for novel therapeutic use but they also provide further opportunity to adopt LDHA inhibition as a strategy for cancer therapy.


Identification of Social Anxiety in Schools: The Utility of a Two-Step Screening Process.
Social anxiety disorder (SAD) is highly prevalent yet largely undetected and untreated in adolescents despite the availability of effective treatments. Implementing interventions in schools enhances recognition and access to treatment for SAD. However, without reliable means to accurately identify youth in need of services, school-based interventions are not feasible. The purpose of this study is to evaluate the utility of a two-step, school-based screening approach to identify youth with SAD. Students at three public high schools were screened with self-report questionnaires or nominated by school personnel. Subsequently, a brief telephone assessment of student symptoms was completed with students' parents. Results showed that using both questionnaires and telephone assessments yielded acceptable detection rates, while school staff nominations were not beneficial. This study provides support for the use of a two-step screening procedure consisting of student self-reports followed by brief parent telephone interviews to identify youth with clinically impairing social anxiety. Implications for enhancing school-based detection of and intervention for socially anxious adolescents are discussed.