Meta-analysis of free-response studies, 1992-2008: assessing the noise reduction model in parapsychology.
We report the results of meta-analyses on 3 types of free-response study: (a) ganzfeld (a technique that enhances a communication anomaly referred to as "psi"); (b) nonganzfeld noise reduction using alleged psi-enhancing techniques such as dream psi, meditation, relaxation, or hypnosis; and (c) standard free response (nonganzfeld, no noise reduction). For the period 1997-2008, a homogeneous data set of 29 ganzfeld studies yielded a mean effect size of 0.142 (Stouffer Z = 5.48, p = 2.13 x 10(-8)). A homogeneous nonganzfeld noise reduction data set of 16 studies yielded a mean effect size of 0.110 (Stouffer Z = 3.35, p = 2.08 x 10(-4)), and a homogeneous data set of 14 standard free-response studies produced a weak negative mean effect size of -0.029 (Stouffer Z = -2.29, p = .989). The mean effect size value of the ganzfeld database was significantly higher than the mean effect size of the standard free-response database but was not higher than the effect size of the nonganzfeld noise reduction database [corrected].We also found that selected participants (believers in the paranormal, meditators, etc.) had a performance advantage over unselected participants, but only if they were in the ganzfeld condition.


Anesthetic and cardiopulmonary effects of intramuscular morphine, medetomidine, ketamine injection in dogs.
To determine the quality and duration of anesthesia and the cardiopulmonary effects of a morphine, medetomidine, ketamine (MMK) combination administered intramuscularly (IM) to dogs. Descriptive injectable anesthetic protocol evaluation. Eight intact adult Beagle dogs: five males, three females. The electrocardiogram, heart rate, direct arterial blood pressure, and core body temperature were monitored in eight chronically instrumented dogs. Each dog received 0.2 mg kg(-1) morphine sulfate, 20 microg kg(-1) medetomidine hydrochloride, and 5 mg kg(-1) ketamine hydrochloride IM. Anesthetic and analgesic effects (clamping the tail and metatarsus) were categorized, and the times to lateral recumbency, orotracheal intubation, extubation, and sternal recumbency were recorded. Respiratory, cardiovascular, temperature, and acid-base variables were recorded 5 minutes before, and 3, 10, 20, 30, 45, 50, and 60 minutes after MMK. Atipamezole, 100 microg kg(-1) IM, was administered 60 minutes after MMK administration and data recorded 10 minutes later. The onset of anesthesia was uneventful and rapid. Time to lateral recumbency was 7.1 +/- 4.1 minutes. The tracheas of four dogs were orally intubated in 5.1 +/- 0.8 minutes. After MMK administration most dogs were unresponsive to noxious stimulation from 20 to 60 minutes and heart rate, cardiac index and venous blood pH were significantly decreased from baseline values. Arterial blood pressure increased initially and then returned to baseline values. Times to extubation (four dogs) and return to sternal recumbency after atipamezole administration were 2.8 +/- 1.8 and 4.3 +/- 4.4 minutes, respectively. The IM administration of MMK produced anesthesia and analgesia in Beagle dogs. Hemodynamic data were within accepted normal values. Atipamezole administration produced rapid return to consciousness in all dogs. Morphine/medetomidine/ketamine may be used for minor medical and surgical procedures requiring short-term anesthesia and analgesia but it is not recommended for medical procedures that are painful.


Endothelial and inflammatory markers in relation to progression of ischaemic cerebral small-vessel disease and cognitive impairment: a 6-year longitudinal study in patients with type 2 diabetes mellitus.
Progression of silent brain infarctions (SBIs) and white-matter lesions (WMLs) seen on brain MRI is associated with an increased risk of cognitive impairment, but their relation to endothelial and inflammatory markers is unknown in type 2 diabetes mellitus. In 190 type 2 diabetic outpatients (mean age 62.7 years), the authors related baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1) and high-sensitivity C-reactive protein (hs-CRP) to subsequent brain MRI findings and cognitive function. The authors assessed incident SBIs and changes in periventricular and subcortical WMLs (PVWMLs and SCWMLs) on MRI performed at baseline and 3 and 6 years. Neuropsychological tests were administered to 83 patients older than 65 years at 6 years. This present study represents an extension of the authors' previously published study. SBIs were observed in 46 patients (24.2%), PVWMLs in 93 (48.9%) and SCWMLs in 87 (45.8%) on baseline MRI. After adjustment for age, gender, hypertension, duration of diabetes, baseline MRI findings and medication use, the relative odds associated with a 1SD increase in sICAM-1 levels at baseline were 1.67 (95% CI 1.02 to 3.05) for SBI progression and 2.17 (95% CI 1.29 to 3.62) for PVWML progression at 6 years. In contrast, baseline hs-CRP levels were significantly associated with SBI progression only at 3 years. Significant trends were observed between quartiles of sICAM-1 at baseline and scores in Digit Symbol substitution (p for trend=0.01). The findings suggest that higher sICAM-1 levels are associated with SBI and PVWML progression, and may predict impairment in psychomotor function in type 2 diabetes.


Effects of progressive resistive exercise in adults living with HIV/AIDS: systematic review and meta-analysis of randomized trials.
This systematic review examined the effectiveness and safety of progressive resistive exercise (PRE) interventions on immunological/virological, cardiopulmonary, weight, and body composition, strength and psychological outcomes in adults living with HIV. Using Cochrane Collaboration protocol, we included randomized controlled trials from 1980-2006 comparing PRE interventions with no PRE or another intervention. Ten studies met inclusion criteria. Seventeen meta-analyses were performed. Results indicated that PRE or a combination of PRE and aerobic exercise may lead to statistically significant increases in weight (WMD: 2.68 kg; 95%CI: 0.40, 4.97) and arm and thigh girth (WMD: 7.91 cm; 95%CI: 2.18, 13.65) among exercisers versus non-exercisers. Trends toward improvement in submaximum heart rate and exercise time also were found. Individual studies suggested that PRE contributed to improved strength and psychological status. Findings are limited to participants who continued to exercise. Progressive resistive exercise appears to be safe and may be beneficial for medically-stable adults living with HIV.


Influence of the pesticides glyphosate, chlorpyrifos and atrazine on growth parameters of nonochratoxigenic Aspergillus section Nigri strains isolated from agricultural soils.
This investigation was undertake to determine the effect of glyphosate, chlorpyrifos and atrazine on the lag phase and growth rate of nonochratoxigenic A. niger aggregate strains growing on soil extract medium at -0.70, -2.78 and -7.06 MPa. Under certain conditions, the glyphosate concentrations used significantly increased micelial growth as compared to control. An increase of about 30% was observed for strain AN 251 using 5 and 20 mg L(-1) of glyphosate at -2.78 MPa. The strains behaved differently in the presence of the insecticide chlorpyrifos. A significant decrease in growth rate, compared to control, was observed for all strains except AN 251 at -2.78 MPa with 5 mg L(-1). This strain showed a significant increase in growth rate. With regard to atrazine, significant differences were observed only under some conditions compared to control. An increase in growth rate was observed for strain AN 251 at -2.78 MPa with 5 and 10 mg L(-1) of atrazine. By comparison, a reduction of 25% in growth rate was observed at -7.06 MPa and higher atrazine concentrations. This study shows that glyphosate, chlorpyrifos and atrazine affect the growth parameters of nonochratoxigenic A. niger aggregate strains under in vitro conditions.


[The importance of therapeutic drug monitoring for psychotropic drugs].
The goal of therapeutic drug monitoring (TDM) is the optimization of the psychiatric pharmacotherapy. Above all, TDM is absolutely indicated for the prevention of adverse drug effects or poisoning. TDM is well-established for therapies with antidepressants, antipsychotic drugs and mood stabilizers. For anti-dementia drugs, anxiolytic drugs, hypnotic drugs and medications for treating addiction, monitoring is currently applied to the interpretation of side effects, drug interactions and to forensic questions.


The ultrastructural defect in conjunctiva from a case of recessive dystrophic epidermolysis bullosa.
The predominant feature in the several forms of epidermolysis bullosa is the formation of cutaneous bullous lesions arising after minimal mechanical trauma. Ocular involvement has been noted as a complication. To our knowledge to date, only four investigators have correlated clinical eye disease with light microscopic findings. Ultrastructure of the ocular lesions has not been described previously. We present four cases of recessive dystrophic epidermolysis bullosa emphasizing their associated ocular complications. Diagnosis was confirmed by skin biopsy specimen and in one patient by demonstrating light and electron microscopic findings in eyelid skin. This tissue exhibited ultrastructural recessive cutaneous lesions; namely, bullous separation occurring below the basal lamina and absence of anchoring fibrils in both bullous and nonbullous areas. By electron microscopy, the conjunctiva in this patient exhibited an absence of clear anchoring fibrils that were numerous in control tissue. This defect may increase the susceptibility of the conjunctiva to minor mechanical trauma, resulting in the bullous and cicatricial changes seen clinically.


Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomsis.
We retrospectively analyzed the clinical data of 112 patients who underwent esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity from October 2011 to June 2013. First, the gastric tube was created with the aid of linear stapling device by removing the stomach and dissecting lymph nodes under laparoscopy and making a 3-4 cm incision through the subxiphoid area in the upper abdomen. Second, the thoracic esophagus and lymph nodes were dissected during thoracoscopic procedure. Gastric tube was inserted into the chest cavity and placed in the posterior mediastinum. The thoracic gastro-esophageal anastomosis was stapled with a circular stapler. Combined laparoscopic-thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis is technically feasible and safe, with minimized trauma, less operative blood loss and quick recovery.


"Not Tied Up Neatly with a Bow": Professionals' Challenging Cases in Informed Consent for Genomic Sequencing.
As the use of genomic technology has expanded in research and clinical settings, issues surrounding informed consent for genome and exome sequencing have surfaced. Despite the importance of informed consent, little is known about the specific challenges that professionals encounter when consenting patients or research participants for genomic sequencing. We interviewed 29 genetic counselors and research coordinators with considerable experience obtaining informed consent for genomic sequencing to understand their experiences and perspectives. As part of this interview, 24 interviewees discussed an informed consent case they found particularly memorable or challenging. We analyzed these case examples to determine the primary issue or challenge represented by each case. Challenges fell into two domains: participant understanding, and facilitating decisions about testing or research participation. Challenges related to participant understanding included varying levels of general and genomic literacy, difficulty managing participant expectations, and contextual factors that impeded participant understanding. Challenges related to facilitating decision-making included complicated family dynamics such as disagreement or coercion, situations in which it was unclear whether sequencing research would be a good use of participant time or resources, and situations in which the professional experienced disagreement or discomfort with participant decisions. The issues highlighted in these case examples are instructive in preparing genetics professionals to obtain informed consent for genomic sequencing.


Value of Neonicotinoid Insecticide Seed Treatments in Mid-South Soybean ( Glycine max ) Production Systems.
Early-season insect management is complex in the Mid-South region of the United States. A complex of multiple pest species generally occurs simultaneously at subthreshold levels in most fields. Neonicotinoids are the only insecticide seed treatment widely used in soybean, Glycine max L., production. An analysis was performed on 170 trials conducted in Arkansas, Louisiana, Mississippi, and Tennessee from 2005 to 2014 to determine the impact of neonicotinoid seed treatments in soybean. The analysis compared soybean seed treated with a neonicotinoid insecticide and a fungicide with soybean seed only treated with the same fungicide. When analyzed by state, soybean yields were significantly greater in all states when neonicotinoid seed treatments were used compared with fungicide-only treatments. Soybean treated with neonicotinoid treatments yielded 112.0 kg ha -1 , 203.0 kg ha -1 , 165.0 kg ha -1 , and 70.0 kg ha -1 , higher than fungicide-only treatments for Arkansas, Louisiana, Mississippi, and Tennessee, respectively. Across all states, neonicotinoid seed treatments yielded 132.0 kg ha -1 more than with fungicide-only treated seed. Net returns from neonicotinoid seed treatment usage were US$1,203 per ha -1 compared with US$1,172 per ha -1 for fungicide-only treated seed across the Mid-South. However, economic returns for neonicotinoid seed treatments were significantly greater than fungicide-only treated seed in 4 out of the 10 yr. When analyzed by state economic returns the neonicotinoid seed treatments were significantly greater than fungicide-only treated seed in Louisiana and Mississippi. These data show that in some areas and years, neonicotinoid seed treatments provide significant economic benefits in Mid-South soybean.


Lysophosphatidic acid induces rapid and sustained decreases in epidermal growth factor receptor binding via different signaling pathways in BEAS-2B airway epithelial cells.
Lysophosphatidic acid (LPA) and epidermal growth factor (EGF) are important mediators of lung cell function and lung diseases. We showed previously that LPA decreases epidermal growth factor receptor (EGFR) binding rapidly in BEAS-2B airway epithelial cells, and this decrease is sustained to at least 18 h. The current studies investigate which LPA signaling pathways mediate the rapid versus sustained decreases in EGFR binding in BEAS-2B cells. The G(i/o) inhibitor pertussis toxin and the Rho kinase inhibitor Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide] had no effect on the rapid or sustained decreases. However, the mitogen-activated protein kinase kinase (MEK) inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)-butadiene ethanolate] decreased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, completely inhibited the rapid decrease in binding, and partially inhibited the sustained decrease. The direct Ca2+- and phospholipid-dependent protein kinase (PKC) activator phorbol-12-myristate-13-acetate stimulated ERK1/2 phosphorylation and decreased EGFR binding at both 15 min and 18 h. Furthermore, inhibitors of PKC partially inhibited ERK1/2 phosphorylation and the 15-min decrease but completely inhibited the 18-h decrease. Inhibitor time course studies showed that PKC induction of the 18-h decrease occurred during the first 3 h of treatment. We showed previously that LPA-stimulated EGFR transactivation contributes to the rapid decrease. Two transactivation inhibitors partially inhibited ERK1/2 phosphorylation, and U0126 partially inhibited EGFR transactivation, indicating that MEK may be involved both upstream and downstream of EGFR activation. Together, the data presented here indicate that LPA mediates the rapid decrease in EGFR binding via EGFR transactivation, MEK/ERK, and PKC, whereas the sustained decrease is regulated primarily by PKC.


Derivation and validation of actionable quality indicators targeting reductions in complications for injury admissions.
Approximately, one out of five patients hospitalized following injury will develop at least one hospital complication, more than three times that observed for general admissions. We currently lack actionable Quality Indicators (QI) targeting specific complications in this population. We aimed to derive and validate QI targeting hospital complications for injury admissions and develop algorithms to identify patient charts to review. We conducted a retrospective cohort study including patients with major trauma admitted to any level I or II adult trauma center an integrated Canadian trauma system (2014-2019). We used the trauma registry to develop five QI targeting deep vein thrombosis/pulmonary embolism (DVT/PE), decubitus ulcers, delirium, pneumonia and urinary tract infection (UTI). We developed algorithms to identify patient charts to revise on consultation with a group of clinical experts. The study population included 14,592 patients of whom 5.3% developed DVT or PE, 2.7% developed a decubitus ulcer, 8.6% developed delirium, 14.7% developed pneumonia and 7.3% developed UTI. The indicators demonstrated excellent predictive performance (Area Under the Curve 0.81-0.87). We identified 4 hospitals with a higher than average incidence of at least one of the targeted complications. The algorithms identified on average 50 and 20 charts to be reviewed per year for level I and II centers, respectively. In line with initiatives to improve the quality of trauma care, we propose QI targeting reductions in hospital complications for injury admissions and algorithms to generate case lists to facilitate the review of patient charts.


CYR61 regulates BMP-2-dependent osteoblast differentiation through the {alpha}v{beta}3 integrin/integrin-linked kinase/ERK pathway.
Osteoporosis is one of the most common bone pathologies. A number of novel molecules have been reported to increase bone formation including cysteine-rich protein 61 (CYR61), a ligand of integrin receptor, but mechanisms remain unclear. It is known that bone morphogenetic proteins (BMPs), especially BMP-2, are crucial regulators of osteogenesis. However, the interaction between CYR61 and BMP-2 is unclear. We found that CYR61 significantly increases proliferation and osteoblastic differentiation in MC3T3-E1 osteoblasts and primary cultured osteoblasts. CYR61 enhances mRNA and protein expression of BMP-2 in a time- and dose-dependent manner. Moreover, CYR61-mediated proliferation and osteoblastic differentiation are significantly decreased by knockdown of BMP-2 expression or inhibition of BMP-2 activity. In this study we found integrin α(v)β(3) is critical for CYR61-mediated BMP-2 expression and osteoblastic differentiation. We also found that integrin-linked kinase, which is downstream of the α(v)β(3) receptor, is involved in CYR61-induced BMP-2 expression and subsequent osteoblastic differentiation through an ERK-dependent pathway. Taken together, our results show that CYR61 up-regulates BMP-2 mRNA and protein expression, resulting in enhanced cell proliferation and osteoblastic differentiation through activation of the α(v)β(3) integrin/integrin-linked kinase/ERK signaling pathway.


The extraction of a neutral metalloproteinase from the involuting rat uterus, and its action on cartilage proteoglycan.
1. Homogenates of rat uteri removed 1 and 2 days post partum were centrifuged at 6000 g. Both pellets and supernatants degraded Azocoll, a general proteinase substrate, at pH 7.5. More than 80% of the total activity was in the pellet fraction. 2. Part of the pellet activity was in a latent form. Trypsin and 4-aminophenylmercuric acetate (a thiol-blocking agent) both activated this latent form, indicating that it is an enzyme--inhibitor complex. An endogenous serine proteinase activated part of the latent enzyme during the assay. 3. The enzyme activity was low before parturition and after involution; it was highest during the first 2 days post partum, when the largest losses of uterine wet weight and matrix macromolecules occur. 4. Up to 70% of the enzyme in the pellets was extracted by heating at 60 degrees C for 4 min in 0.1 M-CaCl2/0.05 M-Tris/HCl, pH 7.5. Approx. 30% of the extracted enzyme was still latent. 5. The extracted enzyme was a metalloproteinase, since it was inhibited completely by 1,10-phenanthroline, but not by inhibitors of thiol or serine proteinases. 6. The enzyme was further purified 15--30-fold by gel chromatography and precipitation with (NH4)2SO4. The apparent molecular weight, estimated by gel filtration, was 24000 for the latent form and 12000 for the active form. The pH optimum was 7--7.5. 7. The enzyme also degraded cartilage proteoglycan. This activity was studied by viscometry and the products were analysed by analytical ultracentrifugation. The major product had a mol.wt. of approx. 100000. The sites of cleavage were in the protein core, since no free oligosaccharides were detected. 8. This neutral metalloproteinase is distinct from uterine collagenase and from a uterine metal-dependent endopeptidase that hydrolyses a heptapeptide related to collagen.


ALDH1A2 Is a Candidate Tumor Suppressor Gene in Ovarian Cancer.
Aldehyde dehydrogenase 1 family member A2 (ALDH1A2) is a rate-limiting enzyme involved in cellular retinoic acid synthesis. However, its functional role in ovarian cancer remains elusive. Here, we found that ALDH1A2 was the most prominently downregulated gene among ALDH family members in ovarian cancer cells, according to complementary DNA microarray data. Low ALDH1A2 expression was associated with unfavorable prognosis and shorter disease-free and overall survival for ovarian cancer patients. Notably, hypermethylation of ALDH1A2 was significantly higher in ovarian cancer cell lines when compared to that in immortalized human ovarian surface epithelial cell lines. ALDH1A2 expression was restored in various ovarian cancer cell lines after treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. Furthermore, silencing DNA methyltransferase 1 (DNMT1) or 3B (DNMT3B) restored ALDH1A2 expression in ovarian cancer cell lines. Functional studies revealed that forced ALDH1A2 expression significantly impaired the proliferation of ovarian cancer cells and their invasive activity. To the best of our knowledge, this is the first study to show that ALDH1A2 expression is regulated by the epigenetic regulation of DNMTs, and subsequently that it might act as a tumor suppressor in ovarian cancer, further suggesting that enhancing ALDH1A2-linked signaling might provide new opportunities for therapeutic intervention in ovarian cancer.


The effect of Ginkgo biloba and Camellia sinensis extracts on psychological state and glycemic control in patients with type 2 diabetes mellitus.
Interest in finding natural antioxidants for use in food or medical materials to prevent free radical imbalance has increased considerably over the past years. The aim of this research was to evaluate changes in glycemic control and psychological state of patients with type 2 diabetes mellitus (T2DM) after use of antioxidant plant preparations. Fifty-six patients with T2DM were randomly allocated to receive standardized Ginkgo biloba L. leaves dry extract, green tea dry extract, or placebo capsules. Diabetes glycemic control measured as glycated hemoglobin (HbA1c) level, antioxidant state and psychological data were evaluated at baseline, after 9 and 18 months of using either antioxidant preparations or placebo. The level of perceived stress lowered significantly after 9 months (p = 0.038) and 18 months (p = 0.030), and the psychological aspect of quality of life significantly improved after 18 months (p = 0.019) of use of G. biloba extrac. No significant differences were detected after using green tea extract. In patients using placebo, significant lowering of HbA1c level was observed after 18 months (p = 0.017). In conclusion, antioxidant G. biloba leaf extract exhibited a mild effect on psychological state and a trend of improving glycemic control in patients with type 2 diabetes mellitus.


Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats.
In concentrations of 10-20 ppm, inhaled nitric oxide (NO) decreases pulmonary artery pressure and attenuates vascular remodeling in pulmonary hypertensive rats. Because NO is potentially toxic, it is important to know whether lower concentrations attenuate vascular remodeling produced by different etiologies. Therefore, we determined the effects of prolonged, small-dose inhaled NO administration on hypoxic and monocrotaline (MCT)-induced pulmonary vascular remodeling. Rats were subjected to normoxia, hypoxia (normobaric 10% oxygen), or hypoxia plus NO in concentrations of 50 ppb, 200 ppb, 2 ppm, 20 ppm, and 100 ppm for 3 wk. A second group of normoxic rats was given MCT (60 mg/kg intraperitoneally) alone or in the presence of 2, 20, and 100 ppm of NO. Subsequently, pulmonary artery smooth muscle thickness and the number of muscular arteries (percentage of total arteries) were determined. Right ventricular hypertrophy was determined by right to left ventricle plus septum weight ratio (RV/LV + S). Pulmonary artery smooth muscle thickness and the percent muscular arteries were increased by hypoxia and MCT. The hypoxic increase in thickness was attenuated by all concentrations of NO, with 100 ppm being greatest, whereas NO had no effect on MCT rats. NO attenuated the increase in percent muscular arteries in hypoxic but not MCT rats. The RV/LV + S was increased by hypoxia and MCT compared with normoxia. Hypoxia-induced RV hypertrophy was decreased by all concentrations of inhaled NO, although attenuation with 50 ppb was less than with 200 ppb, 20 ppm, and 100 ppm. In MCT rats 2 and 100 ppm NO increased RV hypertrophy, whereas 20 ppm had no effect. In conclusion, inhaled NO in concentrations as low as 50 ppb attenuates the pulmonary vascular remodeling and RV hypertrophy secondary to hypoxia. In contrast, concentrations as high as 100 ppm do not attenuate MCT-induced pulmonary remodeling. These results demonstrate that extremely low concentrations of NO may attenuate remodeling but that the effectiveness is dependent on the mechanism inducing pulmonary remodeling. The authors determined whether inhaled NO, a selective pulmonary vasodilator, attenuates pulmonary vascular remodeling caused by two models of pulmonary hypertension: chronic hypoxia and monocrotaline injection. Analysis of pulmonary vascular morphology suggests that very low concentrations of NO effectively attenuate hypoxic remodeling but that NO is not effective in monocrotaline-induced pulmonary remodeling.


Improvement of the physical performance is associated with activation of NO/PGC-1α/mtTFA signaling pathway and increased protein expressions of electron transport chain in gastrocnemius muscle from rats supplemented with L-arginine.
To examine the influence of l-arginine supplementation in combination with physical training on mitochondrial biomarkers from gastrocnemius muscle and its relationship with physical performance. Male Wistar rats were divided into four groups: control sedentary (SD), sedentary supplemented with l-arginine (SDLA), trained (TR) and trained supplemented with l-arginine (TRLA). Supplementation of l-arginine was administered by gavage (62.5mg/ml/day/rat). Physical training consisted of 60min/day, 5days/week, 0% grade, speed of 1.2km/h. The study lasted 8weeks. Skeletal muscle mitochondrial enriched fraction as well as cytoplasmic fractions were obtained for Western blotting and biochemical analyses. Protein expressions of transcriptor coactivator (PGC-1α), transcriptor factors (mtTFA), ATP synthase subunit c, cytochrome oxidase (COXIV), constitutive nitric oxide synthases (eNOS and nNOS), Cu/Zn-superoxide dismutase (SOD) and manganese-SOD (Mn-SOD) were evaluated. We also assessed in plasma: lipid profile, glycemia and malondialdehyde (MDA) levels. The nitrite/nitrate (NOx(-)) levels were measured in both plasma and cytosol fraction of the gastrocnemius muscle. 8-week l-arginine supplementation associated with physical training was effective in promoting greater tolerance to exercise that was accompanied by up-regulation of the protein expressions of mtTFA, PGC-1α, ATP synthase subunit c, COXIV, Cu/Zn-SOD and Mn-SOD. The upstream pathway was associated with improvement of NO bioavailability, but not in NO production since no changes in nNOS or eNOS protein expressions were observed. This combination would be an alternative approach for preventing cardiometabolic diseases given that in overt diseases a profound impairment in the physical performance of the patients is observed.


Physical therapists' perceptions of knowledge and clinical behavior regarding cardiovascular disease prevention.
The study purpose was to assess perceptions of physical therapists (PTs) regarding the role of physical therapy in cardiovascular disease (CVD) prevention. A 25-item survey, validated by expert cardiovascular/pulmonary (CVP) PTs, was sent electronically to 2,673 PTs. Each item represented an element of clinical practice behavior: education of CVD/risk factors (EDCVD), administration of primary CVD prevention (PRECVD), identifying underlying CVD/risk factors (IDCVD), monitoring CV status in patients with CVD (MONCVD). Responses were assigned numeric values (strongly agree = 5 to strongly disagree = 1), and mean element scores were analyzed. Most of the 516 respondents were APTA Section members (34% CVP Section, 42% other Section membership) and worked in academia (53%). Items showing a high (> 95%) level of agreement included patient education of smoking (97%) and monitoring exercise intensity (99%), assessing exercise benefits (99%), clinically identifying obesity (97%) and hypertension (97%), and monitoring CV response to exercise (99%). Items failing to reach 80% overall agreement were patient education of CVD medications (79%) and blood chemistry (72%), and assessing CVD family history (75%), patient BMI (60%), and body composition (33%). Identifying underlying CVD (77.2%) was the only practice behavior failing to reach 80% agreement. Outpatient PTs agreed significantly less to all elements vs. academics, and to IDCVD vs. all PTs except home health. Physical therapists support most CVD prevention behaviors, but not given elements of patient education and identifying underlying CVD/risk factors.


Reliability of a rapid test for the clinical diagnosis of influenza A/H1N1 2009.
The rapid diagnosis of a pandemic influenza A/H1N1 2009 (H1N1pdm) virus infection is required in ambulatory care settings, since early identification can prevent further transmission. However, the sensitivity of rapid influenza diagnostic tests (RIDTs) is still questionable, and specific indicators for H1N1pdm and/or false-negative results by RIDTs have not been clearly determined. From June to December 2009, nasal swabs from 324 patients at Kochi Health Science Center were used for the diagnosis of infection by RIDT and reverse transcription polymerase chain reaction. The sensitivity of the RIDT was determined to be 80.0% and the specificity 97.1%. Multivariate analysis revealed that the frequencies of contagiousness and headache were significant in patients with H1N1pdm infection, in addition to common symptoms of respiratory infection. These data indicated that the H1N1pdm virus had high infectivity and was harmful to the endocranial environment. In the false-negative group, the time interval between onset and consultation was 5.5 ± 6.5 h (median ± interquartile range), which was significantly shorter than the 11.5 ± 7.0 h in the true-positive group. The sensitivity of the RIDT was significantly low during the time-period within 3 h from onset (56.0%); however after 4 h the sensitivity was determined to be >80%. These data indicated that the concentration of the virus in nasal swabs was elevated over the course of the disease. We have demonstrated that the RIDT is reliable for the diagnosis of H1N1pdm infection. Taking into consideration the time interval between onset and consultation and other features of H1N1pdm, such as contagiousness and headache, it may be necessary to re-test RIDT-negative cases later.


Stenotrophomonas maltophilia Pseudo-outbreak at a University Hospital Bronchoscopy Unit in Turkey.
Stenotrophomonas maltophilia is an opportunistic pathogen found predominantly in the environment and hospital setting. Invasive procedures and treatment methods, instruments used for diagnosis and irrational antibiotic use play major roles in the spread of this pathogen. The study aimed to evaluate consecutive S maltophilia isolation from bronchoalveolar lavage samples during bronchoscopy procedure during a week. Four patients consecutively had S maltophilia isolated during bronchoscopy between September 8 and 15, 2012. The identification of the isolates and their antibiotic susceptibility were studied by automated Vitek version 2.0 (Biomerieux, France) system. The clonal relationship between the isolates was studied by enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction (PCR). Four consecutive S maltophilia isolates had identical band patterns and showed clonal relatedness. Bronchoscopy is a common invasive procedure that is utilized in chest diseases departments and intensive care units (ICUs). Contamination may take place due to inappropriate use and cause spread of infectious pathogens. In the current study, we detected consecutive S maltophilia strains with identical band patterns isolated within a week. After appropriate disinfection and cleaning procedures, no further isolation was detected.


Ovitrap surveillance of the dengue vectors, Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus Skuse in selected areas in Bentong, Pahang, Malaysia.
Ovitrap surveillance was conducted in methodically selected areas in Bentong, Pahang, Malaysia from June 2008 till December 2009 in order to identify insular sites with stable Aedes aegypti population. Eleven sites were surveyed in Bentong district, Pahang, and one of these locations (N3º33' E101º54') was found to have an ovitrap index of Ae. aegypti and Aedes albopictus ranging from 8%-47% and 37%-78% respectively, indicating that this site could be a high-risk area for dengue outbreak. Ae. aegypti larvae were found in both indoor and outdoor ovitraps (p>0.05) while significant difference between the populations of Ae. albopictus larvae from indoors and outdoors was observed (p<0.01). Data collected in this study could provide important entomological information for designing an effective integrated vector control programme to combat Aedes mosquitoes in this area.


Experiments of drops impacting a smooth solid surface: a model of the critical impact speed for drop splashing.
Making use of experimental and theoretical considerations, in this Letter we deduce a criterion to determine the critical velocity for which a drop impacting a smooth dry surface either spreads over the substrate or disintegrates into smaller droplets. The derived equation, which expresses the splash threshold velocity as a function of the material properties of the two fluids involved, the drop radius, and the mean free path of the molecules composing the surrounding gaseous atmosphere, has been thoroughly validated experimentally at normal atmospheric conditions using eight different liquids with viscosities ranging from μ=3×10(-4) to μ=10(-2) Pa s, and interfacial tension coefficients varying between σ=17 and σ=72 mN m(-1). Our predictions are also in fair agreement with the measured critical speed of drops impacting in different gases at reduced pressures given by Xu et al. [Phys. Rev. Lett. 94, 184505 (2005).


Reconstitution of the Na+, K+-transport system in artificial membranes.
(1) Purified renal Na+, K+-ATPase was incorporated into phosphatidylcholine-liposomes by using the cholate-dialysis procedure. The passive permeability of the liposomes for Na+ and K+ was determined on 22Na and 86Rb equilibration curves. The rate constant for passive Na-flux was 0.014 min-1 and for K(86Rb)-flux 0.013 min-1. Active transport rates of Na+ and K+ were determined after addition of 3 mM ATP to the liposomes. (2) A micromethod for continuously measuring the ADP production associated with active transport is described. Using this technique, initial velocities of ATP hydrolysis were measured in parallel with Na+-transport and K+-transport. When the Na+-concentration in the incubation medium is increased, the initial velocity of all three processes increase concomitantly. At high turnover, the stoichiometry of coupled Na+, K+-transport catalyzed by the purified reconstituted pump is 2.2Na+: 1K+:1ATP. (3) When the pump has exhausted the vesicular K+-pool, coupled NA+, K+-transport ceases. The pump then carries Na+ uphill without K+-antiport. The Na+: ATP ratio of uncoupled Na+-transport is close to 1:1.


Patient representative programs: a social work perspective.
Patient Representatives are one of the fastest growing new human service occupations functioning in hospital settings. The patient representative's role and function bears certain similarities to social work and has the potential for being seen as pre-empting part of its domain. This article describes the role of patient representatives, reports on a survey of hospitals with patient representative and social work programs and examines some of the issues that this new occupational group may pose for social workers in hospital settings.


Alteration of isocitrate dehydrogenase following acute ischemic injury as a means to improve cellular energetic status in neuroadaptation.
The isocitrate dehydrogenase (IDH) enzymes were initially identified as essential components of the Krebs cycle. IDH mutations were thought to be incompatible with cell survival. However, 90% of glioblastomas were recently shown to be associated with somatic mutations in these enzymes, indicating a possible role for IDH in promoting cellular survival in hypoxic environments. Our proteomic analysis of rats given 10 minutes of middle cerebral artery occlusion to induce transient ischemia demonstrates a significant decrease in IDH expression. We have recapitulated this decrease in an in vitro model using primary cortical neurons exposed to acute oxygen and glucose deprivation. Given the role of IDHs in energy metabolism and antioxidant production, we hypothesize that the IDHs may serve as first-line, rapid-response enzymes that regulate survival in environments of energetic or oxidative stress. In order to identify the specific events that regulate IDH enzymes, HT-22 neural cells were subjected to either a selective energetic challenge or a pure oxidative stress. In response to the non-lethal energetic challenge induced by substituting galactose for glucose, we observed increased IDH1, 2, and 3 expression and cessation of cellular proliferation. No change in expression of any IDH isoform was observed when neural cells were subjected to subtoxic oxidative stress via glutathione depletion. Taken together, these data imply that IDH expression rapidly responds to changes in energetic status, but not to oxidative stress. These data also suggest that IDH enzymes respond not only to allosteric modulation, but can also change patterns of expression in response to moderate stress in an effort to maximize ATP production and survival.


Clinical outcomes of 10 years of cardiac screening in elite New Zealand athletes.
To report findings from the High Performance Sport New Zealand cardiac screening programme, including comparisons between sexes and ethnicities. Retrospective cohort study. Elite Olympic-sport athletes were screened (2012-2022) with personal/family history, physical examination, resting 12-lead ECG and followed from the date of first screening until July 2022. An audit reviewed screening records, including demographic data, ECGs, follow-up and diagnoses. Flagged/equivocal ECGs were re-reviewed (International Criteria). 2075 ECGs from 1189 athletes (53 % female, mean age 21 years; 83 % European, 9 % Māori, 5 % Pacific Islander, 3 % other) were included. No athletes retired for cardiac reasons; there were no cardiac deaths or major cardiac incidents (mean follow-up from first screening: 6.1 years (range: 0.6-10.9 years)). Diagnoses included Wolff-Parkinson-White (WPW) syndrome (0.7 %) and cardiomyopathies (0.3 %). Overall, 3.5 % of ECGs were abnormal, with ECGs of females more commonly abnormal (4.4 % vs 2.5 %, p = 0.02) and with a higher proportion of ECGs with abnormal T-wave inversion (TWI) (3.1 % vs 0.9 %, p < 0.001) compared to males. Of the abnormal TWI in females (all aged ≥16 years), 47 % was limited to V1-V3 with no other abnormalities. Abnormality rates were similar between Māori, Pacific Islander and European athlete ECGs. WPW was the most frequent diagnosis, with very little cardiomyopathy found. The proportion of abnormal ECGs was low overall, but higher in females. This was driven by anterior TWI in V1-V3 which was not associated with diagnoses of conditions associated with sudden cardiac death (SCD). There was no difference in the proportion of abnormal ECGs of Māori or Pacific Island athletes compared to European athletes.


Psychosocial Aspects of Palliative Care.
BACKGROUND: Relief of suffering is a central goal for palliative care. Achievement of this goal can be difficult, however, due to the complex nature of suffering. METHODS: A psychosocial perspective is used to understand suffering and to identify interventions to relieve suffering in patients with advanced disease. RESULTS: Clinical experience and research suggest that attending to the psychosocial aspects as well as the medical aspects of palliative care has the potential of further reducing the suffering experienced by patients with advanced disease. CONCLUSIONS: Suffering is best viewed as a subjective phenomenon t hat can be influenced by biological, psychological and social processes. Interventions in each of these areas can help to relieve patient suffering.


Charge-Transfer Dynamics at the α/β Subunit Interface of a Photochemical Ribonucleotide Reductase.
Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides to provide the monomeric building blocks for DNA replication and repair. Nucleotide reduction occurs by way of multistep proton-coupled electron transfer (PCET) over a pathway of redox active amino acids spanning ∼35 Å and two subunits (α2 and β2). Despite the fact that PCET in RNR is rapid, slow conformational changes mask examination of the kinetics of these steps. As such, we have pioneered methodology in which site-specific incorporation of a [Re(I)] photooxidant on the surface of the β2 subunit (photoβ2) allows photochemical oxidation of the adjacent PCET pathway residue β-Y356 and time-resolved spectroscopic observation of the ensuing reactivity. A series of photoβ2s capable of performing photoinitiated substrate turnover have been prepared in which four different fluorotyrosines (FnYs) are incorporated in place of β-Y356. The FnYs are deprotonated under biological conditions, undergo oxidation by electron transfer (ET), and provide a means by which to vary the ET driving force (ΔG°) with minimal additional perturbations across the series. We have used these features to map the correlation between ΔG° and kET both with and without the fully assembled photoRNR complex. The photooxidation of FnY356 within the α/β subunit interface occurs within the Marcus inverted region with a reorganization energy of λ ≈ 1 eV. We also observe enhanced electronic coupling between donor and acceptor (HDA) in the presence of an intact PCET pathway. Additionally, we have investigated the dynamics of proton transfer (PT) by a variety of methods including dependencies on solvent isotopic composition, buffer concentration, and pH. We present evidence for the role of α2 in facilitating PT during β-Y356 photooxidation; PT occurs by way of readily exchangeable positions and within a relatively "tight" subunit interface. These findings show that RNR controls ET by lowering λ, raising HDA, and directing PT both within and between individual polypeptide subunits.


Hospice care.
Hospice of Peel is a community-based hospice serving a population of between 750-800,000. Hospice care evolved to meet the needs of the terminally ill. It can, and does, take many forms, as you will see in the brief case scenarios detailed below. The individuals and situations described are real and typical of day-to-day-hospice care in a large urban environment. Both the sick and their families are in need of support and assistance to enable them to cope during this time of crisis in their lives. Increased awareness of hospice care is resulting in more and more people with a life-threatening or terminal illness and their families turning to hospice care.


[Renal amyloidosis caused by Ehrlichia canis].
An 8 year old, intact female, Old English Sheepdog was presented with lethargy and chronic weight loss of one year duration. The dog suffered from recurrent fever and a mild peripheral lymphadenopathy. Mild thrombocytopenia, monoclonal hyperglobulinemia and positive Ehrlichia canis antibody titer were indicative of Ehrlichiosis. The patient developed proteinuria and renal failure, which suggested the presence of glomerulopathy. Immunohistochemical staining of renal biopsy specimen demonstrated AA amyloidosis. Chronic ehrlichiosis was suspected to be the cause of the dog's renal amyloidosis.


Mortality Trends in Colorectal Cancer in China During 2000-2015: A Joinpoint Regression and Age-Period-Cohort Analysis.
As lifestyles have increasingly become westernized in China, public health strategies have increasingly focused on cancer prevention. The objective of this study was to describe trends in colorectal cancer (CRC) mortality and the age, period, and cohort effects of CRC mortality in urban and rural China from 2000 to 2015. We collected CRC mortality data from the China Health Statistics Yearbook. We used joinpoint regression analysis to estimate the slope of mortality trends. We then used the age-period-cohort (APC) model with intrinsic estimator to estimate the age, period, and cohort effects of CRC mortality. CRC mortality was higher in urban areas than in rural areas, and the average annual percentage change was also larger in urban areas (4.1%) than in rural areas (3.7%). CRC mortality risk was higher among older adults than among adults aged 20 to 24: the relative risk among adults aged 60 to 64 was 31.09 times higher in urban China and 11.46 times higher in rural China. CRC mortality risk increased with period: compared with period 2000, the relative risk was 1.01 in period 2005, 1.36 in period 2010, and 1.42 in period 2015 in urban China and 1.12 in period 2005, 1.24 in period 2010, and 1.69 in period 2015 in rural China. More recent cohorts had lower CRC mortality risk: compared with the cohort born during 1920-1924, the relative risk of cohort 1950-1954 was 0.70 in urban China and 0.69 in rural China. More interventions to reduce the burden of CRC should be conducted, and it is more necessary for older people and urban residents to adopt a healthy lifestyle in China.


Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: a preliminary study.
The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 +/- 4 kg m(-1) S(-2) and more than 2.5 kg/3 cm(2), respectively. The percent drug content was 98.5 +/- 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically.


[Effects of nifedipine and verapamil on body temperature in cats].
Nifedipine and verapamil injected into the cerebral ventricles of unanaesthetized cats produced a longlasting rise in the body temperature. The hyperthermic effect of nifedipine and verapamil were not dose-dependent. The hyperthermic effect of verapamil was preceded by a shortlasting fall in the body temperature, which was not dose-dependent. Calcium antagonists, nifedipine and verapamil also produced mydriasis, tachypnoea, dyspnoea, ataxia, tremor and muscular weakness. These symptoms were inconsistent and of slight intensity. In agreement with the theory of ionic set point controlling the body temperature, the most probable explanation is that calcium antagonists, nifedipine and verapamil produced changes in the body temperature by acting on sodium and calcium fluxes in the posterior hypothalamus.


Inline classification of polymer films using Machine learning methods.
Improving the sortability of plastic packaging film waste (PPFW) is crucial for increasing the recycling rate in Austria as they account for 150,000 t of the annually produced 300,000 t of plastic packaging waste. Currently PPFW is thermally recovered, as it is impossible to separate the mechanically recyclable monomaterial films from the non mechanically-recyclable multimaterial films. In this study, machine learning models capable of classifying inline into monolayer and multilayer films of PPFW according to their spectral fingerprint taken in transflection were created. Feature selection methods, like PCA and MRMR F-Tests, identified the most relevant spectral ranges for classification, that show the least redundancy and highest relevance. This effective subset of features decreases the required complexity of the model while reducing prediction time without compromising accuracy. The resulting models achieved a prediction accuracy of 85 % on unseen specimens with minimal prediction latency, effectively showing the inline applicability of these models in sorting aggregates.


[Feature of food allergy developed during infancy (2)--acquisition of tolerance against hen's egg, cow's milk, wheat, and soybean up to 3 years old].
Once food elimination is introduced, it is important to know for doctors when patients generally develop oral tolerance against eliminated food. To clarify the point, following study was conducted. We analyzed 304 patient profiles with food allergy in our division between 1994 and 2001. The diagnosis of oral tolerance was determined by the results of food challenges or the accidental episodes of ingestion. By the age of 3 years old, 78% of food allergy patients with soybean, 63% of those with wheat, 60% of those with cow's milk, 51% of those with egg yolk, and 31% of those with egg white developed oral tolerance, respectively. IgE CAP RAST scores against cow's milk, egg yolk, and egg white in the patients without tolerance were significantly higher than those in the patients with tolerance. Patients developed oral tolerance firstly against soybean followed by wheat, cow's milk, egg yolk and egg white during the first 3 years of life. The specific IgE antibody levels against egg and cow's milk are important for the diagnosis of tolerance.


The relationship between social cognitive processes and behavior changes in people with amnestic mild cognitive impairment or dementia using the Edinburgh Social Cognition Test (ESCoT).
People with amnestic mild cognitive impairment (aMCI) or dementia often exhibit a decline in their social abilities, but few tests of social cognition exist that are suitable for clinical use. Moreover, the relationship between changes in behavior and impairments in social cognition is poorly understood. We examined the utility of the Edinburgh Social Cognition Test (ESCoT) in people with aMCI/dementia and explored associations between social cognition performance and behavior changes. We administered the ESCoT and two established social cognition tests (the Reading the Mind in the Eyes and the Social Norms Questionnaire) to 28 people with aMCI or dementia and 28 age and sex matched cognitively healthy controls. Behavior change was measured using a semistructured interview which assesses behavioral abnormalities found in frontotemporal dementia. People with aMCI/dementia were impaired on the ESCoT affective theory of mind, ESCoT total score and the Reading the Mind in the Eyes. Behavior changes in the domains of apathy, loss of sympathy/empathy, perseveration, and psychotic symptoms were associated with poorer affective theory of mind scores. Disinhibition, loss of sympathy/empathy and hyperorality or altered food preferences were associated with cognitive theory of mind. All behaviors were significantly associated with poorer performance on ESCoT total score, but were not associated with performance on the Reading the Mind in the Eyes or the Social Norms Questionnaire. The ESCoT was sensitive to social cognition impairments in people with aMCI/dementia and it relates to behavior change in aMCI/dementia unlike established tests. Different subtests of the ESCoT were related to different behavior changes. These findings suggest that the ESCoT may be a clinically valuable tool when examining social cognition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Oral butorphanol tartrate for the long-term treatment of out-patients with moderate to severe cancer pain.
The safety, tolerance and analgesic efficacy of multiple oral doses of butorphanol tartrate for the long-term treatment of cancer pain were evaluated in this open study. Thirty-five patients were treated with various doses (1 to 12 tablets per day) for 4 to 147 days. The median pain relief was fair, good, very good or excellent in 51% of the patients and poor in 49% of the patients. Global assessments were very similar. No clinically significant changes in blood pressure, weight, blood and urine chemistries were observed. Seventeen patients reported side-effects (only sedation and dry mouth) ranging from mild to severe.


Characterization of noradrenaline-induced increases in intracellular Ca2+ levels in Chinese hamster ovary cells stably expressing human alpha1A-adrenoceptor.
The mechanism for noradrenaline (NA)-induced increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and physiological significance of Na(+) influx through receptor-operated channels (ROCs) and store-operated channels (SOCs) were studied in Chinese hamster ovary (CHO) cells stably expressing human alpha(1A)-adrenoceptor (alpha(1A)-AR). [Ca(2+)](i) was measured using the Ca(2+) indicator fura-2. NA (1 microM) elicited transient and subsequent sustained [Ca(2+)](i) increases, which were inhibited by YM-254890 (G(alphaq/11) inhibitor), U-73122 (phospholipase C (PLC) inhibitor), and bisindolylmaleimide I (protein kinase C (PKC) inhibitor), suggesting their dependence on G(alphaq/11)/PLC/PKC. Both phases were suppressed by extracellular Ca(2+) removal, SK&F 96365 (inhibitor of SOC and nonselective cation channel type-2 (NSCC-2)), LOE 908 (inhibitor of NSCC-1 and NSCC-2), and La(3+) (inhibitor of transient receptor potential canonical (TRPC) channel). Reduction of extracellular Na(+) and pretreatment with KB-R7943, a Na(+)/Ca(2+) exchanger (NCX) inhibitor, inhibited both phases of [Ca(2+)](i) increases. These results suggest that 1) stimulation of alpha(1A)-AR with NA elicits the transient and sustained increases in [Ca(2+)](i) mediated through NSCC-2 that belongs to a TRPC family; 2) Na(+) influx through these channels drives NCX in the reverse mode, causing Ca(2+) influx in exchange for Na(+) efflux; and 3) the G(alphaq/11)/PLC/PKC-dependent pathway plays an important role in the increases in [Ca(2+)](i).


Elliptical orbits of microspheres in an evanescent field.
We examine the motion of periodically driven and optically tweezed microspheres in fluid and find a rich variety of dynamic regimes. We demonstrate, in experiment and in theory, that mean particle motion in 2D is rarely parallel to the direction of the applied force and can even exhibit elliptical orbits with nonzero orbital angular momentum. The behavior is unique in that it depends neither on the nature of the microparticles nor that of the excitation; rather, angular momentum is introduced by the particle's interaction with the anisotropic fluid and optical trap environment. Overall, we find this motion to be highly tunable and predictable.


Helminth genome analysis: the current status of the filarial and schistosome genome projects. Filarial Genome Project. Schistosome Genome Project.
Genome projects for the parasitic helminths Brugia malayi (a representative filarial nematode) and Schistosoma were initiated in 1995 by the World Health Organization with the ultimate objectives of identifying new vaccine candidates and drug targets and of developing low resolution genome maps. Because no genetic maps are available, and very few genes have been characterized from either parasite group, the first goal of both Initiatives has been to catalogue new genes for future placement on chromosome and physical maps. These genes have been identified by the expressed sequence tag (EST) approach, utilising cDNA libraries constructed from diverse life cycle stages. To date, the Initiatives have deposited over 16,000 Brugia ESTs and nearly 8000 Schistosoma ESTs in Genbank's dbEST database, corresponding to 6000 and over 3600 genes respectively (33% of Brugia's estimated gene compliment, 18-24% of that of Schistosoma). Large fragment, genomic libraries have been constructed in BAC and YAC vectors for studies of genomic organization and for physical and chromosome mapping, and public, hypertext genomic databases have been established to facilitate data access. We present a summary of progress within the helminth genome initiatives and give several examples of important gene discoveries and future applications of these data.


Mortality in Patients With Out-of-Hospital Cardiac Arrest Undergoing a Standardized Protocol Including Therapeutic Hypothermia and Routine Coronary Angiography: Experience From the HACORE Registry.
This study sought to analyze the impact of mandatory therapeutic hypothermia and cardiac catheterization in the absence of overt noncardiac cause of arrest as part of the Hannover Cardiac Resuscitation Algorithm before intensive care admission. Despite advanced therapies, out-of-hospital cardiac arrest (OHCA) is still associated with high mortality rates. Recently, the TTM (Target Temperature Management 33°C Versus 36°C After Out-of-Hospital Cardiac Arrest)-trial caused severe uncertainty about the efficacy of and need for therapeutic hypothermia. Furthermore, the role of early coronary angiography in OHCA survivors without ST-segment elevation remains undetermined. In the HACORE (HAnnover Cooling REgistry) we investigated 233 consecutive patients (median age 64 [interquartile range: 53 to 74] years) with OHCA admitted to our institution between January 2011 and December 2015 who were treated according to the algorithm. A total of 73% had ventricular fibrillation as primary rhythm. Return of spontaneous circulation was achieved after 20 (interquartile range: 10 to 30) min. Immediate percutaneous coronary angiography was performed in 96% and coronary angioplasty in 59% of all cases. ST-segment elevation was present in 47%. Critical coronary stenosis requiring percutaneous coronary intervention was present in 67% of patients with and 52% of patients without ST-segment elevation. Overall 30-day intrahospital mortality in this real-world registry was 37%. Patients in our local registry who matched the inclusion/exclusion criteria of the TTM-trial (n = 145) had a markedly lower 30-day mortality (27%) compared with the published trial (44%). Standardized treatment of patients with OHCA following a strict protocol incorporating computed tomography, cardiac catheterization and revascularization, liberal use of active hemodynamic support in presence of shock, and mandatory therapeutic hypothermia results in mortality rates lower than previously reported.


Late subcapital fracture of the neck of the femur--a rare complication of Ender nailing.
This appears to be the first report of a late subcapital fracture of the femoral neck after Ender nailing. The contributing factors are stress concentration and osteomalacia. The understanding of this late complication is helpful to the use of Ender nail in stable fixation of selected cases of trochanteric fractures.


Drinking course in alcohol-dependent men from adolescence to midlife.
Most studies of alcoholism course are based on clinical populations (characterized by severe and chronic alcohol-related problems) or community samples generally covering a short period of time. The current study assessed variations in drinking behaviors from adolescence to midlife in a community sample, describing age of "drinking firsts" (e.g., first alcoholic drink) as well as frequency and duration of periods of abstinence, alcohol dependence (AD) and nonproblem drinking. Participants were 354 males with lifetime diagnoses of AD (mean age 50.35) from the Vietnam Era Twin Registry who were assessed regarding alcohol use, abuse and dependence histories (DSM-IV). Using a modified version of Skinner's Lifetime Drinking History, drinking history was reported in terms of distinct drinking periods (phases). Participants reported, on average, 4.18 phases, each lasting 8.22 years, and 12.78 years of AD. More than 60% experienced increases in AD symptoms at least once in successive phases, but only a third of those increases were extreme. In contrast, extreme decreases in AD symptoms were reported by more than 50% of participants. Further, half indicated that they had transitioned from both fewer to greater and from greater to fewer AD symptoms during their drinking years; 8.2% reported no changes in AD symptoms. Results reflect a wide variation in drinking behaviors among AD men as well as frequent fluctuations in course within individuals' drinking histories. Findings do not support a universal developmental model of alcoholism; notably, they provide counterevidence to the disease model concept of alcoholism course as progressive and chronic.


Body Mass Index Effects Kruger's Criteria in Infertile Men.
The aim of this study is to evaluate the relationship between sperm parameters and body mass index (BMI) in the male spouses with infertility complaints, who had reffered to our clinic. The male spouses from 159 couples reffering to our clinic because of infertility, during a six-month period, were included in the study. In this prospective case control study, the included men were categorized as non-obese (BMIP<25 kg/m2), overweight (BMI 25-29 kg/m2) and obese (BMI ≥30 kg/m2) according to their BMIs. The assessed sperm parameters consisted of; sperm concentration, Kruger morphology, progressive motility level, and volume pH levels. The statistical significant level was set as less than 0.05. The assessed group consisted of 159 patients applying to our clinic with infertility symptoms. Fifty-three non-obese, 53 overweight and 53 obese men were eligible for the study. There was statistically significant differences in sperm volume (P<0.001), progressive motility (P<0.001), postwash sperm count (P<0.001) and Kruger (P<0.001) morphology among the patient groups grouping according to the BMI levels. In this study, increased BMI was associated with decreased semen quality, affecting volume, concentration, and motility. further studies with a wider range of prospective cases need to be conducted in order to investigate the effects on male fertility in more detail.


Induction of basic fibroblast growth factor mRNA by basic fibroblast growth factor in Müller cells.
To investigate the induction of basic fibroblast growth factor (bFGF) gene expression in cultured rat Müller cells by bFGF and to study the mechanism of induction. Müller cells from 1- to 3-day-old Sprague-Dawley rats were isolated and cultured with Dulbecco's modified Eagle's medium with 10% fetal calf serum. Cultured cells were identified by immunocytochemistry using antibodies against vimentin, carbonic anhydrase II, and glutamine synthetase. Cells of passages 1 through 4 were treated with bFGF, the protein kinase C (PKC) inhibitor, H-7; calphostin C, or the PKC activator, PMA; and protein kinase A (PKA) inhibitor, H-89; as well as the adenylate cylase activator, forskolin; or the adenylate cyclase inhibitor, SQ22536. Northern blot analysis was performed to determine the mRNA expression of bFGF, ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF). Addition of bFGF to culture medium induced bFGF gene expression in a dose- and time-dependent manner. Induction of bFCF mRNA started at a bFGF concentration of 0.1 ng/ml. The bFGF mRNA level was elevated by 2-fold at 1 ng/ml of bFGF, 2.8-fold at 5 ng/ml, and reached a peak of 4-fold at 10 ng/ml and 3.7-fold at 50 ng/ml. At 10 ng/ml of bFGF, induction of bFGF mRNA was observed as early as 2 hours (2-fold) after treatment. The bFGF mRNA level continued to increase to 3.7-fold by 4 hours, and reached a maximum of 4.4-fold by 8 hours. A slow decline of the bFGF mRNA level was observed after 8 hours of bFGF treatment (3.5-fold by 12 hours, and 3-fold by 24 hours). This induction of bFGF gene expression was blocked by PKC inhibitors H-7 (30 microM). The PKC activator PMA (0.1 microM) also upregulated bFGF gene expression, but the effects of bFGF and PMA were not additive. An adenylate cyclase inhibitor, SQ22536 (100 microM), did not inhibit bFGF-induced bFGF gene expression. Although forskolin (5 microM), an adenylate cyclase activator, also upregulated the level of bFGF mRNA, the effects of forskolin and bFGF were additive. In addition, no inhibitory effect on bFGF-induced expression of bFGF mRNA was found using H-89 (1 microM). Exogenous bFGF did not alter the mRNA levels of CNTF and BDNF. These results indicate that bFGF induces bFGF gene expression in cultured rat Müller cells through PKC activation. The authors' findings raise the possibility that Müller cells in vivo also respond to available bFGF (for example, that released from the endogenous reservoirs in the case of injury) or to exogenous bFGF by producing more bFGF, which could in turn promote photoreceptor survival.


Palmitoylation mechanisms in dopamine transporter regulation.
The neurotransmitter dopamine (DA) plays a key role in several biological processes including reward, mood, motor activity and attention. Synaptic DA homeostasis is controlled by the dopamine transporter (DAT) which transports extracellular DA into the presynaptic neuron after release and regulates its availability to receptors. Many neurological disorders such as schizophrenia, bipolar disorder, Parkinson disease and attention-deficit hyperactivity disorder are associated with imbalances in DA homeostasis that may be related to DAT dysfunction. DAT is also a target of psychostimulant and therapeutic drugs that inhibit DA reuptake and lead to elevated dopaminergic neurotransmission. We have recently demonstrated the acute and chronic modulation of DA reuptake activity and DAT stability through S-palmitoylation, the linkage of a 16-carbon palmitate group to cysteine via a thioester bond. This review summarizes the properties and regulation of DAT palmitoylation and describes how it serves to affect various transporter functions. Better understanding of the role of palmitoylation in regulation of DAT function may lead to identification of therapeutic targets for modulation of DA homeostasis in the treatment of dopaminergic disorders.


Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia.
Despite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia. To investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56). Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter. Patients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers. A defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.


Shared Bacterial and Viral Respiratory Agents in Bighorn Sheep (Ovis canadensis), Domestic Sheep (Ovis aries), and Goats (Capra hircus) in Montana.
Transmission of infectious agents from livestock reservoirs has been hypothesized to cause respiratory disease outbreaks in bighorn sheep (Ovis canadensis), and land management policies intended to limit this transmission have proven controversial. This cross-sectional study compares the infectious agents present in multiple populations of bighorn sheep near to and distant from their interface with domestic sheep (O. aries) and domestic goat (Capra hircus) and provides critical baseline information needed for interpretations of cross-species transmission risks. Bighorn sheep and livestock shared exposure to Pasteurellaceae, viral, and endoparasite agents. In contrast, although the impact is uncertain, Mycoplasma sp. was isolated from livestock but not bighorn sheep. These results may be the result of historic cross-species transmission of agents that has resulted in a mosaic of endemic and exotic agents. Future work using longitudinal and multiple population comparisons is needed to rigorously establish the risk of outbreaks from cross-species transmission of infectious agents.


[Age dynamics and seasonal variations of parameters of cerebral circulation in children and adolescents from European north].
Age dynamics and seasonal variations in cerebral blood flow was studied by means of transcranial Doppler in 95 the natives of the Arkhangelsk region school students aged 7 to 18 years. The results of longitudinal (from 2005 to 2014) study of students are presented. The linear blood flow velocity (BFV) showed gradual declining from junior to senior school age, and BFV were in the middle cerebral artery below average, and in the basilar artery--above mid latitude standards. The influence of the seasonal factor is more pronounced in the younger (for boys) and intermediate (for girls) age group and leveled in the older group. The largest seasonal changes were obtained in BFV in carotid arteries, the relative constancy--in BFV in the basilar artery. Estimated by the resistivity index RI circulatory resistance in the younger and intermediate school students groups decreased in the carotid arteries in the spring and summer, and in the posterior cerebral artery territory--in the winter. BFV rate variability identifies groups of children with varying degrees of "sensitivity" to the influence of seasonal factors.


COVID-19 and its cardiovascular effects: a systematic review of prevalence studies.
A small minority of people with coronavirus disease 2019 (COVID-19) develop a severe illness, characterised by inflammation, microvascular damage and coagulopathy, potentially leading to myocardial injury, venous thromboembolism (VTE) and arterial occlusive events. People with risk factors for or pre-existing cardiovascular disease may be at greater risk. To assess the prevalence of pre-existing cardiovascular comorbidities associated with suspected or confirmed cases of COVID-19 in a variety of settings, including the community, care homes and hospitals. We also assessed the nature and rate of subsequent cardiovascular complications and clinical events in people with suspected or confirmed COVID-19. We conducted an electronic search from December 2019 to 24 July 2020 in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, covid-19.cochrane.org, ClinicalTrials.gov and EU Clinical Trial Register. We included prospective and retrospective cohort studies, controlled before-and-after, case-control and cross-sectional studies, and randomised controlled trials (RCTs). We analysed controlled trials as cohorts, disregarding treatment allocation. We only included peer-reviewed studies with 100 or more participants, and excluded articles not written in English or only published in pre-print servers. Two review authors independently screened the search results and extracted data. Given substantial variation in study designs, reported outcomes and outcome metrics, we undertook a narrative synthesis of data, without conducting a meta-analysis. We critically appraised all included studies using the Joanna Briggs Institute (JBI) checklist for prevalence studies and the JBI checklist for case series. We included 220 studies. Most of the studies originated from China (47.7%) or the USA (20.9%); 9.5% were from Italy. A large proportion of the studies were retrospective (89.5%), but three (1.4%) were RCTs and 20 (9.1%) were prospective. Using JBI's critical appraisal checklist tool for prevalence studies, 75 studies attained a full score of 9, 57 studies a score of 8, 31 studies a score of 7, 5 studies a score of 6, three studies a score of 5 and one a score of 3; using JBI's checklist tool for case series, 30 studies received a full score of 10, six studies a score of 9, 11 studies a score of 8, and one study a score of 5 We found that hypertension (189 studies, n = 174,414, weighted mean prevalence (WMP): 36.1%), diabetes (197 studies, n = 569,188, WMP: 22.1%) and ischaemic heart disease (94 studies, n = 100,765, WMP: 10.5%) are highly prevalent in people hospitalised with COVID-19, and are associated with an increased risk of death. In those admitted to hospital, biomarkers of cardiac stress or injury are often abnormal, and the incidence of a wide range of cardiovascular complications is substantial, particularly arrhythmias (22 studies, n = 13,115, weighted mean incidence (WMI) 9.3%), heart failure (20 studies, n = 29,317, WMI: 6.8%) and thrombotic complications (VTE: 16 studies, n = 7700, WMI: 7.4%). This systematic literature review indicates that cardiometabolic comorbidities are common in people who are hospitalised with a COVID-19 infection, and cardiovascular complications are frequent. We plan to update this review and to conduct a formal meta-analysis of outcomes based on a more homogeneous selected subsample of high-certainty studies.


Growth rates of Sulfolobus acidocaldarius in nature.
Turnover times for water passing through several Sulfolobus acidocaldarius-containing springs were determined by measuring the dilution rates of small amounts of sodium chloride that were added to the springs. Chloride was diluted out exponentially, while concentrations of the bacteria remained constant. Additionally, temperature, pH, and chemical composition of the springs also remained constant during the time that the chloride was being diluted. The springs are thus steady-state systems, and since the rates of bacterial growth must be at least equal to the chloride dilution rates, minimal doubling times for the bacterial populations can be calculated. Half-times for chloride dilution, equivalent to bacterial doubling times, were on the order of 10 to 20 h for springs ranging in volume from about 20 to 2,000 liters, but approximately 30 days for two larger springs of about 1 million liters. Formaldehyde-fixed cells of a serologically distinguishable strain of S. acidocaldarius were also added as markers to four of the smaller springs, and the dilution rates of these bacteria were compared with the chloride dilution rates. The rates agreed reasonably well, thus verifying the growth rates obtained from the chloride dilution rates. In three springs, exponential growth was studied by draining the springs and allowing them to refill with bacteria-free water. Exponential doubling times were on the order of a few hours, much more rapid than steady-state doubling times. The methods used in this work may have wider utility in aquatic environments.


Expression of multidrug resistance-related genes (mdrl, MRP, GST-pi and DNA topoisomerase II) in urothelial cancers.
To characterize the multidrug resistance (MDR) phenotype in human urothelial cancers, the expression levels of four MDR-related genes (multidrug resistance, mdrl; multidrug resistance-associated protein, MRP; glutathione S-transferase-pi, GST-pi; and DNA topoisomerase II, topo II) were analysed in urothelial cancers. Fifty-two tumour tissue and three normal urothelial mucosa samples were obtained from 44 patients with urothelial cancers. The expression of each gene was analysed with a reverse-transcription polymerase chain reaction (RT-PCR) method using beta 2-microglobulin (b2m) mRNA as an endogenous control. Levels of expression were expressed as the ratio of the specific products of the target gene to those specific to b2m. In primary urothelial cancer tissues, the mean (SD) expression of mdrl, MRP, GST-pi and topo II relative to b2m expression were 0.067 (0.061), 0.27 (0.23), 0.35 (0.31) and 0.12 (0.05), respectively. The mean expressions of MRP and GST-pi were higher than those of mdrl and topo II. The mean ratios of mdrl/b2m, MRP/b2m, GST-pi/b2m and topo II/b2m in normal urothelial mucosa were 0.06 (0.03), 0.12 (0.09), 0.30 (0.32) and 0.14 (0.01), respectively. There was no significant association of the expression of each gene with either the grade or extent of the primary tumour. The level of MRP expression in each sample was correlated significantly with the expression of mdrl and GST-pi in the urothelial cancers (r = 0.637 and 0.537, respectively). Chemotherapy did not markedly influence the induction of expression of the MDR-related genes, except for one case in which mdrl expression was 15 times greater than before chemotherapy. The expression of GST-pi in the patients not receiving chemotherapy was significantly higher than in those that did. These results suggest that the activation of MRP and GST-pi expression occurs during the tumorigenesis of urothelial cancers and that it may confer de novo and acquired drug resistance on urothelial cancers. These results should provide further insight into the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis and tumour progression.


Performance analysis of coexisting IEEE 802.15.4-based health monitoring WBANs.
Wireless Body Area Networks (WBANs) for health monitoring systems are required to meet stringent performance demands regarding the tradeoff between reliability, latency, and power efficiency. WBANs feature limited range and bandwidth and they are prone to interference. Considering the life-critical nature of some WBAN systems, we present an in-depth investigation of the situations where the dynamic coexistence of multiple WBANs may severely affect their performances. In this paper, we analytically study the effect of coexistence on the operation of WBANs. We present a mathematical analysis to precisely obtain the probabilities of successful communication and validate this analysis through simulation. Our simulation analysis indicates that in the default mode of operation, coexistence of three WBANs can lead to the loss of 20-85% of data transmissions for typical sensor configurations.


The influence of local electric fields on photoinduced absorption in dye-sensitized solar cells.
The dye-sensitized solar cell (DSC) challenges conventional photovoltaics with its potential for low-cost production and its flexibility in terms of color and design. Transient absorption spectroscopy is widely used to unravel the working mechanism of DSCs. A surprising, unexplained feature observed in these studies is an apparent bleach of the ground-state absorption of the dye, under conditions where the dye is in the ground state. Here, we demonstrate that this feature can be attributed to a change of the local electric field affecting the absorption spectrum of the dye, an effect related to the Stark effect first reported in 1913. We present a method for measuring the effect of an externally applied electric field on the absorption of dye monolayers adsorbed on flat TiO(2) substrates. The measured signal has the shape of the first derivative of the absorption spectra of the dyes and reverses sign along with the reversion of the direction of the change in dipole moment upon excitation relative to the TiO(2) surface. A very similar signal is observed in photoinduced absorption spectra of dye-sensitized TiO(2) electrodes under solar cell conditions, demonstrating that the electric field across the dye molecules changes upon illumination. This result has important implications for the analysis of transient absorption spectra of DSCs and other molecular optoelectronic devices and challenges the interpretation of many previously published results.


[Relations between the methods of isolating Brucella lipopolysaccharides and their effect on hemopoiesis in mice].
The comparative study of the effect produced by different lipopolysaccharide (LPS) preparations obtained from B. melitensis virulent strain 565 and B. abortus vaccine strain 19-BA on hematopoiesis in mice was made. The LPS preparations were obtained (1) by Boivin's technique, (2) by Westphal's technique and (3) by mild alkaline hydrolysis of Bovin's active complex, this technique having been developed at the Brucellosis Laboratory of the Gamaleya Research Institute of Epidemiology and Microbiology. All tests (the spleen endocolonization test, the hydroxyurea kill test, the determination of the content of splenic colony-forming units in the peripheral blood) showed that LPS from B. melitensis virulent strain 565 had a more pronounced disturbing effect on hematopoiesis than LPS from B. abortus vaccine strain 19-BA. Among the LPS preparations obtained by different methods, the one obtained with the use of the technique developed at the Gamaleya Research Institute of Epidemiology and Microbiology proved to have the mildest effect on hematopoiesis, probably due to the partial saponification of the lipid component of LPS. Lipid A in a dose of 0.1-10 micrograms produced no activating effect on the hematopoiesis characteristics under study. None of the LPS preparations proved to be capable of stimulating the formation of transitory endogenous colonies in the spleen of mice.


Power to detect linkage based on multiple sets of data in the presence of locus heterogeneity: comparative evaluation of model-based linkage methods for affected sib pair data.
The development of rigorous methods for evaluating the overall strength of evidence for genetic linkage based on multiple sets of data is becoming increasingly important in connection with genomic screens for complex disorders. We consider here what happens when we attempt to increase power to detect linkage by pooling multiple independently collected sets of families under conditions of variable levels of locus heterogeneity across samples. We show that power can be substantially reduced in pooled samples when compared to the most informative constituent subsamples considered alone, in spite of the increased sample size afforded by pooling. We demonstrate that for affected sib pair data, a simple adaptation of the lod score (which we call the compound lod), which allows for intersample admixture differences can afford appreciably higher power than the ordinary heterogeneity lod; and also, that a statistic we have proposed elsewhere, the posterior probability of linkage, performs at least as well as the compound lod while having considerable computational advantages. The companion paper (this issue, pp 217-225) shows further that in application to multiple data sets, familiar model-free methods are in some sense equivalent to ordinary lod scores based on data pooling, and that they therefore will also suffer dramatic losses in power for pooled data in the presence of locus heterogeneity and other complicating factors.


Morphine's effects on differential serial compound conditioning and reflex modification of the rabbit's (Oryctolagus cuniculus) nictitating membrane response.
This study sought to determine the effects of morphine (0, 2, and 5 mg/kg) on (a) differential classical conditioning of the rabbit's (Oryctolagus cuniculus) nictitating membrane response (NMR) to the serial compounds A-X-unconditioned stimulus (US) and B-X-US (Experiment 1) and (b) the reflex modification effects of the compounds and their components (Experiment 2). These experiments determined specifically morphine's effects on the distinctiveness and time course of stimulus representations by examining morphine's dose-response effect on (a) differential responding to A and B and their conditional control over responding to X within the compounds and (b) the unconditioned excitatory effects of the compounds and their components as assessed by their ability to modify the amplitude of the unconditioned NMR. The results of these experiments indicate that morphine, in a dose-dependent manner, can operate to profoundly attenuate the distinctiveness and persistence (short-term memory) of stimulus representations.


Does the cranial suspensory ligament have a role in cryptorchidism?
The cranial suspensory ligament (CSL) is a fibromuscular structure anchoring the embryonic gonad to the posterior abdominal wall in male and female mammals. Its persistence in females is believed to be responsible for retaining the ovaries within the abdomen, while its regression in males permits testis descent. Embryonic loss of the CSL in males is believed to be an androgen-dependent event, and failure of this process has been proposed as a cause of cryptorchidism. The present study demonstrates that the nuclei of mesenchymal cells in the caudal part of the CSL are immunoreactively positive for androgen receptor. We examined the effects of exposure of the non-steroidal antiandrogen flutamide during the period from gestational day 10 to birth on the development of the CSL and on testis descent. Exposure of male Albino Swiss rats to the antiandrogen flutamide during this period resulted in feminization of the external genitalia and the suppression of growth of the testes and male reproductive tracts. In adulthood, testes were found to be located in diverse positions including normal scrotal (50%), intra-abdominal (10%) and ectopic suprainguinal (40%). The CSL of the testis persisted into adulthood in all flutamide-treated males, regardless of testis location. In all cases, the ligament consisted of bundles of smooth muscle fibres in the retroperitoneal fat of the posterior abdominal wall. These findings suggest that androgen blockade during embryonic development interferes with testicular descent, but that maldescent cannot be correlated with either the persistence of the CSL of the testis or its structure.


A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes.
Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS+). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS+ and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS+ phenotype with learning difficulties and extended behavioural presentation. The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA-evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS+ and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism.


[Characteristics of neurons of the lateral suprasylvian region of the cat cerebral cortex sensitive to the movement of black stimuli].
Visually sensitive neurons of the lateral suprasylvian area were investigated in cats with pretrigeminal brain stem sections. Nearly 25% of a neuron population responding to the visual stimuli revealed great sensitivity to movement of black stimuli across their receptive fields. These neurons were called "black-sensitive". As a rule, they had either a low-level or no background activity. Nearly 89% of these neurons revealed direction-selective properties. The most characteristic feature of "black-sensitive" neurons was a change in response patterns with the reversion of the stimulus contrast.


Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial.
The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir's mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. ClinicalTrials.gov, NCT04575597.


Intestinal anastomosis in children: a comparative study between two different techniques.
The aim of this study was to compare the incidence of surgical complications between two different surgical techniques for intestinal anastomosis in children. This was a clinically controlled, randomized study with blind follow-up from 18 to 36 months performed at the Reference Government Hospital in Mexico City. Eighty-six children required intestinal anastomosis, ages ranged between 1 month and 16 years, with emergency or elective surgery. Anastomoses of duodenum, rectum, with enteroplasty or protected with a proximal stoma were excluded. Two randomized groups were formed: (1) anastomosis with one layer of suture (Gambee stitches) and (2) with two layers of suture (first with Connel-Mayo stitches then with Lembert). Both groups were controlled in the principal variables without differences, and the follow-up concerning postoperative recovery was blind for the surgical team. Forty-two cases in group 1 and 44 in group 2 were compared. Intestinal dehiscence was found in 5 of 86 (5.8%), two from group I and three from group II (P value, not significant). Surgical time for anastomosis with one layer was an average of 26 minutes versus 43 minutes with two layers (P<.001). There were no stenoses within the follow-up period. This study proves that intestinal anastomosis with one layer of suture is as safe as anastomosis with two layers in children, and the time spent for completion of the procedure is significantly less with one plane of suture. For those reasons, it is the method of choice for intestinal anastomosis in children.


The social determinants of otitis media in aboriginal children in Australia: are we addressing the primary causes? A systematic content review.
Aboriginal and Torres Strait Islander children experience some of the highest rates of otitis media in the world. Key risk factors for otitis media in Aboriginal children in Australia are largely social and environmental factors such as overcrowded housing, poverty and limited access to services. Despite this, little is known about how to address these risk factors. A scoping content review was performed to determine the relationship between social determinants of health and otitis media in Aboriginal and Torres Strait Islander children as described by peer-reviewed and grey literature. Search terms were established for location, population and health condition. The search terms were used to conduct a literature search using six health research databases. Following the exclusion process, articles were scoped, analysed and categorised using scoping parameters and a social determinants of health framework. Housing-related issues were the most frequently reported determinants for otitis media (56%). Two articles (4%) directly investigated the impact of social determinants of health on rates of otitis media within Aboriginal and Torres Strait Islander children. The majority of the literature (68%) highlights social determinants as playing a key role in the high rates of otitis media seen in Aboriginal populations in Australia. There were no intervention studies targeting social determinants as a means to reduce otitis media rates among Aboriginal and Torres Strait Islander children. This review identifies a disconnect between otitis media drivers and the focus of public health interventions within Aboriginal and Torres Strait Islander populations. Despite consensus that social determinants play a key role in the high rates of otitis media in Aboriginal and Torres Strait Islander children, the majority of intervention studies within the literature are focussed on biomedical approaches such as research on vaccines and antibiotics. This review highlights the need for otitis media intervention studies to shift away from a purely biomedical model and toward investigating the underlying social determinants of health. By shifting interventions upstream, otitis media rates may decrease within Aboriginal and Torres Strait Islander children, as focus is shifted away from a treatment-focussed model and toward a more preventative model.


No association between neuregulin 1 and psychotic symptoms in Alzheimer's disease patients.
Alzheimer's disease (AD) patients commonly suffer from behavioral and psychological symptoms of dementia (BPSD). Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD patients with psychosis. In this study, we analyzed NRG1 variants in AD patients with and without psychosis. Our large cohort of 399 probable AD patients had longitudinal information on the BPSD, which was used to dichotomize patients into whether they had ever suffered from psychotic symptoms within the study period. The NRG1 single nucleotide polymorphisms rs3924999, rs35753505 (SNP8NRG221533) and the microsatellites 478B14-848 and 420M9-1395 were investigated for association with psychosis using genotype, allele, and haplotype analyses. No associations were found between any of these variants or haplotypic combinations with delusions, hallucinations, psychosis, or elation/mania in our cohort. Positive associations with polymorphisms and haplotype combinations of NRG1 have been reported in psychiatric disorders. One previous study found an association with psychosis in AD, with a SNP outside the haplotype block first reported for association with schizophrenia. We found no association with any of these variants in our cohort. Further investigations of this region on chromosome 8 are clearly required, with replication in different large longitudinal cohorts.