Subregion-Specific Proteomic Signature in the Hippocampus for Recognition Processes in Adult Mice.
The hippocampal formation is a brain structure essential for higher-order cognitive functions. It has a complex anatomical organization and cellular composition, and hippocampal subregions have different properties and functional roles. In this study, we used SWATH-MS to determine whether the proteomes of hippocampus areas CA1 and CA3 can explain the commonalities or specificities of these subregions in basal conditions and after recognition memory. We show that the proteomes of areas CA1 and CA3 are largely different in basal conditions and that differential changes and dynamics in protein expression are induced in these areas after recognition of an object or object location. While changes are consistent across both recognition paradigms in area CA1, they are not in area CA3, suggesting distinct proteomic responses in areas CA1 and CA3 for memory formation.


[Short-term effects of exposure to urban air pollution on human health in Europe. The APHEA Projects (Air Pollution and Health: a European Approach].
During the '80s, evidence was collected that air pollutants concentrations close to, or lower than, air quality standards could negatively influence public health at short term, i.e. within a few days. The European Union financed, between 1993 and 1995, the study "Short term effects of Air Pollution on Health: a European Approach using epidemiological time-series data" (APHEA-1 project), involving more than 25 millions inhabitants in 15 cities, investigated between 1977 and 1991. In this paper, the main results, already published in various scientific journals, are reported. The health effects were studied as mortality for natural causes, cardiovascular and respiratory diseases, and as emergency hospital admissions for all respiratory diseases, bronchial asthma, and chronic obstructive pulmonary disease (COPD). The pollutants whose measures were available for the analysis are sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM) measured either as black smoke or total suspended particulate, and ozone (O3). The analysis was carried out by each participating group following a detailed protocol, defined during various workshops, through the construction of Poisson regression models, adjusted for autocorrelation and overdispersion, accounting for variables influencing the daily count of deaths, such as long time trends, season, temperature, day of the week. This paper reports the results of the meta-analysis, performed using the values of each city, as relative risk of dying or being admitted to hospital associated with increases of 50 micrograms/m3 in the 24 hours average concentrations of each pollutant. The daily number of natural deaths was associated with increases in the levels of PM, SO2, O3, and NO2. Cardiovascular and respiratory deaths were associated with increases of the levels of PM, SO2, and O3; cardiovascular deaths were associated also with increases of NO2 concentrations. Emergency hospital admissions for the whole group of respiratory disorders are less consistently associated with PM, SO2, and NO2, whereas there is evidence of association with O3. COPD admissions are related to the air pollutant levels, especially those of O3. Lastly, NO2 levels may play a role in exhacerbating asthma, and SO2 levels can have an effect on asthma in children. A second study is currently going on, involving over 40 millions residents in 34 cities. The aims of this project are: to evaluate the dose-response relationship, to investigate on synergy among pollutants, on the "harvesting" phenomenon, on the geographical differences inside Europe and with the U.S. through the collaboration with a similar American study now in progress. The existence of an association between daily variations in the levels of urban air pollution and adverse health effects was confirmed in Europe. This association is weak, but it involves the whole resident population, so it is a major cause of concern from the public health point of view.


Abatement of particulate matter emission from experimental aviary housings for laying hens by spraying rapeseed oil.
In alternative systems for laying hens, concentrations and emission rates of particulate matter (PM) give reason for concern with regard to working conditions, bird health and productivity, and health of residents living near farms. Previously, we found that spraying a film of rapeseed oil onto the litter of broilers could substantially reduce PM concentrations and emissions. The objective of this study was to establish dose-response effects of oil spraying in aviaries on concentrations and emission rates of PM with aerodynamic diameters less than 10 μm (PM10) and 2.5 μm (PM2.5), on stockmen's exposure to PM10, on egg production, exterior quality and behavior of the hens, and on the litter. An experiment was carried out with 4 treatments: 0 (control), 15, 30, and 45 mL/m2 per d (oil treatments). Each treatment was applied in 2 rooms with different aviary systems (8 rooms in total). The experiment was repeated during a second period, both lasting 35 days. From d 11 to d 35, oil was applied daily using a spraying gun. Applying 15, 30, or 45 mL/m2 per d significantly reduced emission rates of PM10 by 27, 62, and 82%, and emission rates of PM2.5 by 71, 83, and 94%, respectively. No significant effects of oil spraying were found on mortality, egg production, dust bathing behavior, scratching behavior, plumage soiling, DM content of the litter, or friability of the litter. A significant worsening of the plumage condition was found only for the body spot back/wings/tail (not for: throat/neck, chest/breast, or legs) in the 45 mL/m2 per d treatment. Egg quality shifted significantly towards more second-class eggs in the oil treatments (1.9% versus 1.4%; P = 0.004). Remarkably, foot soiling decreased with increasing oil application. In conclusion, PM concentrations and emission rates in aviaries can be effectively reduced by spraying 15 to 30 mL/m2 per d with minor side effects within a 25 d application period.


Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF alpha-dependent cytotoxicity. 1. Potential role of salivary glands.
Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor beta (TGF beta), showed that only pretreatment of MCs with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity. Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously.


Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function.
Tissue-resident memory (TRM) CD8 T cells provide early frontline defense against regional pathogen reencounter. CD8 TRM are predominantly parked in nonlymphoid tissues and do not circulate. In addition to this anatomic difference, TRM are transcriptionally and phenotypically distinct from central-memory T cells (TCM) and effector-memory T cells (TEM). Moreover, TRM differ phenotypically, functionally, and transcriptionally across barrier tissues (e.g., gastrointestinal tract, respiratory tract, urogenital tract, and skin) and in non-barrier organs (e.g., brain, liver, kidney). In the brain, TRM are governed by a contextual milieu that balances TRM activation and preservation of essential post-mitotic neurons. Factors contributing to the development and maintenance of brain TRM, of which T cell receptor (TCR) signal strength and duration is a central determinant, vary depending on the infectious agent and modulation of TCR signaling by inhibitory markers that quell potentially pathogenic inflammation. This review will explore our current understanding of the context-dependent factors that drive the acquisition of brain (b)TRM phenotype and function, and discuss the contribution of TRM to promoting protective immune responses in situ while maintaining tissue homeostasis.


Ascites in patients undergoing intermittent haemodialysis at Kenyatta National Hospital.
In a two-year-period (August 1984 to August 1986), 77 patients were admitted into the maintenance haemodialysis programme at Kenyatta National Hospital. 24 (31.5%) of these had ascites during haemodialysis. Nine (37.5%) of the patients who had ascites had prior peritoneal dialysis, while 15 (62.5%) had congestive cardiac failure at the time of development of the ascites. In 21 (87.5%), the ascites responded to therapy with diuretics, salt and fluid restriction, antibiotics when indicated and to ultrafiltration during dialysis. In 3 (12.5%) of the patients, the ascites developed in the absence of any predisposing cause. The ascites progressively increased in amount and was associated with marked wasting. These patients were considered to have refractory ascites of haemodialysis.


Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats.
In adult rats, 50,000 units of recombinant interleukin-1 beta (IL-1 beta) injected into the brain parenchyma produced an intense meningitis and disruption of the blood-CSF barrier by 4 h. No increase in vascular permeability to horseradish peroxidase or leukocyte recruitment was observed at the site of injection. By contrast, in juvenile rats, 100 units of IL-1 beta injected into the striatum gave rise to a large increase in blood-brain barrier permeability and recruitment of polymorphonuclear neutrophils into the tissue around the injection site by 4 h. This effect was also accompanied by a marked meningitis. The injection of 100 units of IL-1 beta into neonatal (2-h-old) rats gave rise to an increase in permeability of vessels to serum proteins in the meninges, but no increase in vascular permeability was observed at the injection site. The IL-1 beta-induced increases in vessel permeability in the meninges, parenchyma, and choroid plexus were polymorphonuclear neutrophil dependent, since leukocyte depletion by irradiation or polymorphonuclear neutrophil anti-serum pre-treatment eliminated the response in the juvenile animals and in the adults. Seventy-five thousand units of murine tumour necrosis factor-alpha injected into the parenchyma of both adults and juvenile animals failed to induce an increase in blood-brain barrier permeability or polymorphonuclear neutrophil recruitment, but did give rise to a mild meningitis. These findings demonstrate clear differences in the responsiveness of different CNS compartments to IL-1 beta. Furthermore, while tumour necrosis factor-alpha and IL-1 beta might have been expected to exhibit similar proinflammatory effects in the CNS, this is not the case. We also show, for the first time, that age has a significant effect on the response to a cytokine. The "window of susceptibility' to an inflammatory stimulus in juvenile rats, if paralleled in humans, may be a major factor in the increased susceptibility of children to trauma or to infectious insults to the CNS.


Proton-Coupled Electron Transfer in Electrocatalytic Water Splitting.
Proton-coupled electron transfer (PCET) plays a crucial role in a diverse array of natural and artificial energy conversion processes. Herein, we will introduce the fundamentals of electrochemical PCET with a focus on its role in water splitting. Besides, perspectives of future development of PCET are presented with regard to the investigation of reaction mechanisms and the design of advanced electrocatalysts.


[Malaria imported by immigrants].
The immigrants from endemic zones who live in Europe are those with the greatest risk of acquiring malaria during trips to their countries, since they usually travel for longer than other travellers and to zones and under conditions of greater risk. The figures for the years 2002-2004 in Spain indicate that P. falciparum is the most diagnosed species. Africa is the continent from which most cases are imported and immigrants contribute 34-41% of all cases.


Acetylation controls Notch3 stability and function in T-cell leukemia.
Post-translational modifications of Notch3 and their functional role with respect to Notch3 overexpression in T-cell leukemia are still poorly understood. We identify here a specific novel property of Notch3 that is acetylated and deacetylated at lysines 1692 and 1731 by p300 and HDAC1, respectively, a balance impaired by HDAC inhibitors (HDACi) that favor hyperacetylation. By using HDACi and a non-acetylatable Notch3 mutant carrying K/R(1692-1731) mutations in the intracellular domain, we show that Notch3 acetylation primes ubiquitination and proteasomal-mediated degradation of the protein. As a consequence, Notch3 protein expression and its transcriptional activity are decreased both in vitro and in vivo in Notch3 transgenic (tg) mice, thus impairing downstream signaling upon target genes. Consistently, Notch3-induced T-cell proliferation is inhibited by HDACi, whereas it is enhanced by the non-acetylatable Notch3-K/R(1692-1731) mutant. Finally, HDACi-induced Notch3 hyperacetylation prevents in vivo growth of T-cell leukemia/lymphoma in Notch3 tg mice. Together, our findings suggest a novel level of Notch signaling control in which Notch3 acetylation/deacetylation process represents a key regulatory switch, thus representing a suitable druggable target for Notch3-sustained T-cell acute lymphoblastic leukemia therapy.


Application of plastic polymers in remediating wine with elevated alkyl-methoxypyrazine levels.
3-Alkyl-2-methoxypyrazines (MPs) are odour-active compounds that elicit atypical green aromas and flavours in some wines, and are resilient to removal using traditional wine-making approaches. They originate either as contaminants from Coccinellidae beetles inadvertently introduced during wine processing ("ladybug taint") or as grape-derived constituents that are undesirable at elevated levels. In this study we investigated the capacity of a selection of plastic polymers to reduce concentrations of three MPs: isopropyl methoxypyrazine (IPMP), secbutyl methoxypyrazine (SBMP) and isobutyl methoxypyrazine (IBMP). In Trial 1, red wine was spiked with IPMP (20 ng/l), SBMP (20 ng/l) and IBMP (20 ng/l), then separately treated with 13 plastic polymers (surface area 350 cm(2)/l). Three polymers were then identified for further testing based on the results from Trial 1: silicone, ethylene and vinyl acetate (EVA) and a poly-lactic acid-based biodegradable polymer. In Trial 2, the efficacy of these selected polymers to reduce MP levels in red wine was tested as a function of contact time. Solid-phase micro-extraction multi-dimensional GC-MS was used to measure MP levels before and after treatment with the polymers. Results showed significant reductions in all target odorants after 24 h treatment: silicone reduced IPMP and IBMP by 96% and 100%, respectively, while the biodegradable polymer decreased IPMP and IBMP concentrations by 52% and 36%, respectively. EVA was less effective in lowering MP levels (7% IPMP and 23% IBMP after 24 h). Taken overall, the data suggest the potential for the use of poly-lactic acid and silicone in treating wines contaminated by ladybug taint, as well as in reducing high levels of grape-derived MPs.


Parietal low beta rhythm provides a dynamical substrate for a working memory buffer.
Working memory (WM) is a component of the brain's memory systems vital for interpretation of sequential sensory inputs and consequent decision making. Anatomically, WM is highly distributed over the prefrontal cortex (PFC) and the parietal cortex (PC). Here we present a biophysically detailed dynamical systems model for a WM buffer situated in the PC, making use of dynamical properties believed to be unique to this area. We show that the natural beta1 rhythm (12 to 20 Hz) of the PC provides a substrate for an episodic buffer that can synergistically combine executive commands (e.g., from PFC) and multimodal information into a flexible and updatable representation of recent sensory inputs. This representation is sensitive to distractors, it allows for a readout mechanism, and it can be readily terminated by executive input. The model provides a demonstration of how information can be usefully stored in the temporal patterns of activity in a neuronal network rather than just synaptic weights between the neurons in that network.


Static stability of novel uncemented elbow hemiarthroplasty stabilized with ligament reconstruction.
The purpose of this study was to create a model to simulate treatment of unreconstructable distal humerus fractures with hemiarthroplasty. Stability was restored with a latest plate-system that simultaneously tensions medial and lateral collateral ligament grafts. Static varus and valgus elbow stability was tested in 11 cadaver elbows with intact ligaments and capsule at 5 flexion angles (0°, 30°, 60°, 90°, 120°). The elbows were then destabilized via release of all ligaments and capsular attachments. The distal humerus articular cartilage was excised and replaced with an uncemented hemiarthroplasty. Ligament reconstruction was subsequently performed, and elbow stability was measured and compared to the native state. Dimensions of the hemiarthroplasty component were compared to native elbow dimensions to assess and quantify any existing relationship to elbow stability. A hemiarthroplasty was implanted in all specimens. A size mismatch occurred between the distal humerus trochlea and the olecranon fossa in all specimens and averaged 6.3 mm. Following ligament reconstruction, specimens reproduced the flexion angle-dependent stability of native elbows to both varus and valgus stress. On the medial side, elbow joint stability in mid-flexion was approximately 7% tighter after hemiarthroplasty. Laterally, the elbow was approximately 15% tighter after hemiarthroplasty and demonstrated peak stability in full flexion. The 3 assessed hemiarthroplasty components and bony dimensions did not exhibit any relationship between implant-bone mismatch and elbow stability after ligamentous reconstruction. Cadaveric elbow specimens underwent uncemented hemiarthroplasty with soft tissue stabilization with a novel technique for ligament reconstruction. Following hemiarthroplasty and ligament reconstruction, these specimens maintained secure fixation between ligament and bone. Static stability was maintained at varying degrees of elbow flexion regardless of variable mismatch between the hemiarthroplasty component and the native olecranon fossa.


Absorption and metabolization of sex hormones and their transformation into contraceptive technologies: the paths taken by medical thought in Brazil.
The article analyses knowledge assimilation and the development of clinical and research practices relating to sex hormones among Brazilian gynaecologists. It discusses the paths taken by medical thought from the reception of the hormones to their transformation into contraceptives. Our objective is to comprehend styles of introducing and disseminating medical technologies in the area of reproductive health in Brazil. It uses methods of historical analysis and takes as its source the Anais Brasileiros de Ginecologia, a journal published between 1936 and 1970. From the outset, the accompaniment of scientific breakthroughs in relation to sex hormones and their use to treat diverse female illnesses played a key role in the rapid medical acceptance of hormonal contraception. Scientific and technical questions (side effects, dosages) and the demographic issue formed part of the majority of the debates. Objections from the Catholic Church were considered but did not set the agenda of medical thought on contraceptives. The quest to consolidate gynaecology as a scientific, modern and cosmopolitan area of expertise, along with sanitary and demographic motives that allowed contraceptives to be classed as ethical drugs, are identified as processes underlying the assimilation and metabolization of sex hormones as hormonal contraceptives.


Self medication practices among workers in a tertiary hospital in Nigeria.
Studies in most developing countries revealed (70-95%) of illnesses are treated through self medication. Poor accessibility to medical services have been associated with this practice. This study determines the pattern of self medication among workers at the University College Hospital, Ibadan, Nigeria. In a cross sectional study, workers were selected using a stratified random sampling technique. A high proportion of workers (73%) reported the practice of self medication and 95.6% of them correctly use appropriate drugs. About 80% of these workers stock their drugs at home. Also, 80.4% procure their drugs in chemist shops. A higher proportion of workers directly involved with medical care services (90.9%) practice self medication compared to those involved with non-medical care services (62.9%), P < 0.01. Also, the higher the education of workers the more is the proportion that practice self medication. (P < 0.05). Self-medication is commonly practiced among the hospital population who have relatively easy access to medical care services. Thus self medication may be a real health option.


Hydroethanolic extract of Baccharis trimera ameliorates alcoholic fatty liver disease in mice.
Ethanol abuse is a serious public health problem that is associated with several stages of alcoholic liver disease (ALD) and a high incidence of morbidity and mortality. Alcoholic fatty liver disease (AFLD), the earliest stage of ALD, is a multifactorial injury that involves oxidative stress and disruptions of lipid metabolism. Although benign and reversible, no pharmacological treatments are available for this condition. In the present study, we induced AFLD in mice with 10% ethanol and a low-protein diet and then orally treated them with a hydroethanolic extract of Baccharis trimera (HEBT; 30 mg kg-1). HEBT reversed ethanol-induced oxidative stress in the liver, reduced lipoperoxidation, normalized GPx, GST, SOD and Cat activity, and GSH and total ROS levels. The reverser effect of HEBT was observed upon ethanol-induced increases in the levels of plasma and hepatic triglycerides, plasma cholesterol, plasma high-density lipoprotein, and plasma and hepatic low-density lipoprotein. Moreover, HEBT increased fecal triglycerides and reduced the histological ethanol-induced lesions in the liver. HEBT also altered the expression of genes that are involved in ethanol metabolism, antioxidant systems, and lipogenesis (i.e., CypE1, Nrf2, and Scd1, respectively). No signs of toxicity were observed in HEBT-treated mice. We propose that HEBT may be a promising pharmacological treatment for AFLD.


The causes of hypoxemia of COVID-19 ARDS: a combined MIGET and Dual-Energy CT study.
Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch and diffusion limitation) in COVID-19 ARDS is currently lacking. In this study we aimed to understand what is the relative contribution of the different mechanisms of hypoxemia in this disease and what is their relationship with the distribution of tissue and blood within the lung. We prospectively enrolled 10 patients with COVID-19 ARDS, intubated for <7 days. We performed the Multiple Inert Gas Elimination Technique (MIGET) and a Dual-Energy Computed Tomography (DECT), which was quantitatively analyzed both for the tissue and blood volume. We also recorded variables related to the respiratory mechanics and invasive hemodynamics (PiCCO). The population (51±15 years, PaO2/FiO2 172±86 mmHg) had a mortality of 50%. MIGET showed a shunt of 25±16% and a deadspace of 53±11%. The ventilation and perfusion were mismatched (LogSD, Q 0.86±0.33). Unexpectedly, we also found evidence of diffusion limitation/post-pulmonary shunting (Predicted PaO2= 1.6*measured PaO2 - 37.5 mmHg). In the well-aerated regions, the blood volume was in excess compared to the tissue, while the opposite happened in the atelectasis. Shunt was proportional to the blood volume of the atelectasis (R 2=0.70, p=0.003). VA/QT mismatch was correlated with the blood volume of the poorly-aerated tissue (R 2=0.54, p=0.016). The overperfusion coefficient was related to PaO2/FiO2 (R 2=0.66, p=0.002), excess tissue mass (R 2=0.84, p<0.001) and to EtCO2/PaCO2 (R 2=0.63, p=0.004). These data support the hypothesis of a highly multifactorial genesis of hypoxemia. Evidence from autoptic studies (i.e., opening of Intrapulmonary Bronchopulmonary Anastomosis) may explain the unexpected post-pulmonary shunting. The hyperperfusion might be related to the disease severity.


Neighborhood context and adjustment in African American youths from single mother homes: the intervening role of hopelessness.
African American youths from single mother homes are more likely to live in neighborhoods characterized by greater risk and fewer resources than youth from two parent homes or European American youths; in turn, such adverse conditions are associated with increased adjustment problems. Despite this well-established vulnerability, relatively little is known about variables linking neighborhood context to youth adjustment. With the aim of identifying a potential youth-focused intervening variable amenable to intervention, this study examined the intervening role of hopelessness in the association between neighborhood context and adjustment problems in a sample of 171 African American youths (11-16 year olds) from single mother homes. Findings revealed direct associations between neighborhood context and youth adjustment, as well as indirect associations through youth hopelessness, although findings varied by the marker of neighborhood context (sense of community or perceived crime) and adjustment (internalizing or externalizing problems). Building on prior work noting that hopelessness is amenable to psychosocial intervention, the present findings suggest that hopelessness may afford a valuable target for prevention and intervention programming among African American youths from single mother homes in the context of adverse neighborhood conditions.


Activity of the delta-opioid receptor is partially reduced, whereas activity of the kappa-receptor is maintained in mice lacking the mu-receptor.
Previous pharmacological studies have indicated the possible existence of functional interactions between mu-, delta- and kappa-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of delta- and kappa-opioid receptors in mice lacking the mu-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPgammaS binding and adenylyl cyclase inhibition showed that functional coupling of delta- and kappa-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[D-penicillamine2, D-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR -/- mice. delta-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR -/- mice. Analgesic and respiratory responses produced by the selective kappa-agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of delta- and kappa-receptor signaling properties in mice lacking mu-receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the kappa-agonist further suggest that the kappa-receptor mainly acts independently from the mu-receptor in vivo. Reduced delta-analgesia and the absence of delta-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between mu-receptors and central delta-receptors in specific neuronal pathways.


Seasonal and monthly variability in the incidence of venous thromboembolism. A systematic review and a meta-analysis of the literature.
Many studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to assess the presence of an infradian rhythm of this disease. MEDLINE and EMBASE databases were searched up to January 2010. Monthly and seasonal variation in the incidence of VTE were analysed. We included studies analysing seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors independently reviewed and extracted data. Seventeen studies for a total of about 35,000 patients were included. Twelve studies analysed the seasonal variation and 10 studies the monthly variation of VTE. Our results showed a significantly increased incidence of VTE in winter (chi-square 146.04, p <0.001), with a relative risk (RR) of VTE of 1.143 (99% CI [1.141, 1.144]), and a significantly increased incidence of VTE in January (chi-square 232.57, p <0.001) with an RR of VTE of 1.194 (99% CI 1.186, 1.203). Subgroup analyses including only idiopathic venous thromboembolic events confirmed the results of principal analyses. In conclusion, our data support the presence of an infradian pattern in the incidence of venous thromboembolic events, with a significantly higher risk in Winter and in January. Future studies are needed to better clarify the mechanisms behind this pattern.


Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation.
Human leukocyte antigen (HLA)-E belongs, with HLA-G and HLA-F, to the non-classic major histocompatibility complex (MHC) class I (Ib) molecules, broadly defined by a limited polymorphism and a restricted pattern of cellular expression. In contrast to HLA-G, the expression and function of HLA-E and HLA-F in physiologic and pathologic processes remain poorly established. In the present study, we show that HLA-E protein expression in normal human nonlymphoid organs is mainly restricted to endothelial cells (ECs). HLA-E is also basally expressed by B and T lymphocytes, natural killer (NK) cells and by macrophages. We demonstrate that tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interferon gamma (IFNgamma) up-regulate the cell-surface expression of HLA-E on ECs in vitro and induce the release of soluble HLA-E (sHLA-E). HLA-E up-regulation protects IFN-gamma-activated ECs from NK-mediated cell lysis, while sHLA-E protects bystander cells. Finally, sHLA-E is not detected in normal sera, and increased serum levels correlate with disease activity in patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis. Thus, HLA-E expression and release of sHLA-E are features of EC activation and emphasize immunoregulatory functions of the endothelium. The present identification of soluble HLA-E molecules may have important implications in understanding the pathogenesis of immune-mediated vascular diseases and for the diagnosis and monitoring of patients.


All groin swellings are not lipoma.
An interesting case of an abdominal wall swelling near an old operative scar showing epithelial and stromal cells. In this present paper, fine needle aspiration cytology of an inguinal swelling is discussed which may often create diagnostic confusion.


TELO-SCOPE study: a randomised, double-blind, placebo-controlled, phase 2 trial of danazol for short telomere related pulmonary fibrosis.
Recent discoveries have identified shortened telomeres and related mutations in people with pulmonary fibrosis (PF). There is evidence to suggest that androgens, including danazol, may be effective in lengthening telomeres in peripheral blood cells. This study aims to assess the safety and efficacy of danazol in adults and children with PF associated with telomere shortening. A multi-centre, double-blind, placebo-controlled, randomised trial of danazol will be conducted in subjects aged >5 years with PF associated with age-adjusted telomere length ≤10th centile measured by flow fluorescence in situ hybridisation; or in children, a diagnosis of dyskeratosis congenita. Adult participants will receive danazol 800 mg daily in two divided doses or identical placebo capsules orally for 12 months, in addition to standard of care (including pirfenidone or nintedanib). Paediatric participants will receive danazol 2 mg/kg/day orally in two divided doses or identical placebo for 6 months. If no side effects are encountered, the dose will be escalated to 4 mg/kg/day (maximum 800 mg daily) orally in two divided doses for a further 6 months. The primary outcome is change in absolute telomere length in base pairs, measured using the telomere shortest length assay (TeSLA), at 12 months in the intention to treat population. Ethics approval has been granted in Australia by the Metro South Human Research Ethics Committee (HREC/2020/QMS/66385). The study will be conducted and reported according to Standard Protocol Items: Recommendations for Interventional Trials guidelines. Results will be published in peer-reviewed journals and presented at international and national conferences. NCT04638517; Australian New Zealand Clinical Trials Registry (ACTRN12620001363976p).


Determination of carbendazim residues in the eggs, liver and pectoral muscle of Japanese quail (Coturnix coturnix japonica).
The effect of carbendazim, a widely applied cereal seed dressing agent, was studied in Japanese quail (Coturnix coturnix japonica) during an overall period of eight weeks, consisting of a four-week feeding phase and a subsequent four-week excretion period. Body mass and feed consumption of the birds were monitored and residues of the active ingredient were determined by an analytical chemical method. During the eight-week study period, changes (either decrease or increase) directly attributable to the toxic effects of carbendazim were not found either in body mass or in feed consumption. Active ingredient levels exceeding the limit of detection were found in the liver (average: 0.0262 mg/kg) and pectoral muscle (average: 0.0236 mg/kg) of the birds and also in the egg (0.0338 mg/kg) samples. From the results it can be concluded that through the consumption of cereal seeds dressed with carbendazim, this active ingredient can be incorporated into the tissues of animals. Via the food chain, carbendazim can also enter the human organism, where it may cause various pathological changes in interaction with other chemicals.


Mechanistic insights into Pb(II) removal from aqueous solution by green reduced graphene oxide.
As one of the important contaminants in wastewater, Pb(II) becomes a severe public health problem because of its non-biodegradable and persistent nature. In this study, reduced graphene oxide (RGO) prepared using green tea extract was successfully used to remove Pb(II) from aqueous solutions. A 96.6% of Pb(II) was removed at 10 mg/L Pb(II) and 0.4 g/L RGO with pH 4.5 at 30 °C, and the adsorption of Pb(II) by RGO followed pseudo-second-order kinetics. To confirm the removal mechanism, various methods (Transmission Electron Microscopy, Raman spectroscopy and X-ray diffraction) were used to characterize RGO before and after Pb(II) adsorption. The results showed that the surface of RGO after Pb(II) adsorption became rougher, and the interlayer spacing increased from 0.36 nm to 0.40 nm, indicating that Pb(II) was adsorbed on the surface and between the layers of RGO. Finally, the adsorption mechanism of Pb(II) by RGO was proposed, Pb(II) was adsorbed on the surface of RGO via the electrons on the π-bond on RGO and the interaction of Pb(II) with oxygen-containing functional groups, which were supported by the Fourier Transform Infrared and X-ray photoelectron spectroscopy results.


Acute Effects of Active, Ballistic, Passive, and Proprioceptive Neuromuscular Facilitation Stretching on Sprint and Vertical Jump Performance in Trained Young Soccer Players.
Oliveira, LP, Vieira, LHP, Aquino, R, Manechini, JPV, Santiago, PRP, and Puggina, EF. Acute effects of active, ballistic, passive, and proprioceptive neuromuscular facilitation stretching on sprint and vertical jump performance in trained young soccer players. J Strength Cond Res 32(8): 2199-2208, 2018-The aim of this study was to compare the acute effects of active (AC), ballistic (BA), passive (PA), and proprioceptive neuromuscular facilitation (PNF) stretching methods on performance in vertical jumping, sit and reach, and sprinting in young soccer players. Twelve trained soccer players (17.67 ± 0.87 years) participated in the study. The jump height (H), peak power (PP), and relative power (RP) in the squat jump (SJ) and countermovement jump (CMJ), the range of motion (ROM), the rating of perceived exertion (RPE), and time (seconds) in 10-20-30-m sprints were evaluated. Significant differences (p < 0.05) in H were found in the comparisons between the PA and control (CO) condition for the SJ. For the CMJ, differences in H were observed between the PA and CO, and PNF with CO and BA, and in the PP between the PNF and CO, AC, and BA, as well as in the RP between the PNF and BA. Significant increases in ROM were found in the AC, BA, PA, and PNF compared with the CO. In relation to RPE, higher scores were reported in the PA and PNF conditions compared with the AC and BA. No significant differences were found in 10-20-30-m sprints. Therefore, the AC and BA methods can be used before vertical jump and sprint activities, with the aim of increasing flexibility. However, the PA and PNF methods should be avoided because of subsequent negative effects on vertical jump performance.


Selective growth of Au nanograins on specific positions (tips, edges and facets) of Cu2O octahedrons to form Cu2O-Au hierarchical heterostructures.
This communication demonstrates a novel strategy for the selective growth of Au nanograins (AuNGs) on specific positions (tips, edges and facets) of Cu(2)O octahedrons to form Cu(2)O-Au hierarchical heterostructures. The surface energy distribution of the octahedrons generally follows the order of γ((facets)) < γ((edges)) < γ((tips)) and leads to the preferential growth and evolution of the heterostructures. These novel Cu(2)O-Au hierarchical heterostructures show fascinating degradations of methylene blue (MB), due to the suppressed electron/hole recombination phenomena and the highly efficient light harvesting.


Effects of taurine in glucose and taurine administration.
Taurine has several biological processes such as hypoglycemic action, antioxidation, detoxification, etc. To assess the effect of taurine administration on the guinea pigs with hyperglycemia, blood glucose, C-peptide levels together with morphologic alterations in the pancreatic ultrastructure were investigated in terms of hypoglycemic action and malondialdehyde and total sulfhydryl group levels with regard to oxidation-antioxidation relation. Animals were divided into four groups of six. Glucose supplementation group was administrated a single dose of glucose (400 mg/kg, i.p.) injection. Glucose and taurine supplementation group was administrated glucose treatment (a single dose, 400 mg/kg, i.p.) following taurine (a single dose, 200 mg/kg, i.p.). Taurine and glucose supplementation group was administered taurine treatment (a single dose, 200 mg/kg, i.p.) following glucose treatment (a single dose, 400 mg/kg, i.p.). Control animals received no treatment. Blood samples were collected at the end of the experiments for the determination of glucose, C-peptide (indicator of insulin secretion), lipid peroxidation (thiobarbituric acid reactive substances), and total sulfhydryl groups levels. Pancreatic tissue samples were then collected and processed for transmission electron microscopy. The findings showed that glucose supplementation following taurine administration significantly decreased blood glucose level by increasing C-peptide level and the pancreatic secretion stimulated morphologically and insignificantly changed thiobarbituric acid reactive substances and total sulfhydryl group levels. These observations suggest that taurine administration may be useful in hyperglycemia because of its hypoglycemic and protective effects.


Response rates to a questionnaire 26 years after baseline examination with minimal interim participant contact and baseline differences between respondents and nonrespondents.
Research on response rates to surveys mailed to study participants decades after baseline examination, with minimal interim contact, is limited. This paper documents response rates to a 26-year follow-up survey of surviving participants from a large cohort in Illinois and compares baseline characteristics of nonrespondents and respondents. Mortality follow-up of the Chicago Heart Association Detection Project in Industry 1967-1973 cohort involved minimal or no participant contact since baseline. In 1996, a 26-year follow-up questionnaire was mailed to all surviving participants aged 65 years or older. Current addresses were obtained from the Health Care Financing Administration for 96.5 percent of 12,409 participants in our analyses. Total response rates were 59.8 percent and, for participants for whom Health Care Financing Administration addresses were available, 60.8 percent. A higher response rate was obtained for younger recipients, men, Whites, more-educated persons, nonsmokers, and those with a better cardiovascular risk profile at baseline. A graded negative relation was found between number of cardiovascular risk factors at baseline and response rates obtained in 1996. Use of Health Care Financing Administration records as an additional follow-up method and factors that influence response rates are discussed. In conclusion, long-term follow-up of older surviving participants is feasible if current addresses can be obtained from standardized sources.


[Bone lithiasis in the period of the Enlightenment: D.F.J.B. Trehet].
To briefly describe the life and works of D.F.J.B. Trehet, a physician of the city of Rouen (France), who was the first to describe the "osseous points" in a renal calculus. Trèhet has not been recognized or referenced for this original observation in the urological publications. Trehet lived in the period of the Enlightenment and endured the upheavals of the French Revolution. Data gleaned from several sources have permitted and elaborate description of this French physician from both the social and professional perspectives. After completing his studies at the Hôtel Dieu in Rouen, D.F.J.B. Trehet pursued his education at the School of Health in Paris. He read his doctorate's thesis at the Paris School of Medicine in 1803 and published his observation of a renal calculus "with osseous points" in 1812. Other studies by D.F.J.B. Trehet were also published in Le Journal de Médecine, Chirurgie et Pharmacie. D.F.J.B. Trehet should be recognized as the first to describe an osseous renal calculus.


alpha-Internexin, a 66-kD intermediate filament-binding protein from mammalian central nervous tissues.
In this paper we describe a 66-kD protein that co-purifies with intermediate filaments from rat optic nerve and spinal cord but can be separated further by ion-exchange chromatography. This protein is distinct from the 68-kD neurofilament subunit protein as judged by isoelectric focusing, immunoblotting, peptide mapping, and tests of polymerization competence. This protein is avidly recognized by the monoclonal anti-intermediate filament antigen antibody, previously demonstrated to recognize a common antigenic determinant in all five known classes of intermediate filaments. Also, when isolated this protein binds to various intermediate filament subunit proteins, which suggests an in vivo interaction with the intermediate filament cytoskeleton, and it appears to be axonally transported in the rat optic nerve. Because of this ability to bind to intermediate filaments in situ and in vitro we have named this protein alpha-internexin. A possible functional role for the protein in organizing filament assembly and distribution is discussed.


Hierarchical porous ZIF-8 for hydrogen production via the hydrolysis of sodium borohydride.
Hydrides show good performance for hydrogen gas storage/release. However, hydrogen gas release from hydrides via hydrolysis is a slow process and thus requires a catalyst. Herein, terephthalic acid (TPA) is used for the synthesis of a hierarchical porous zeolitic imidazolate framework (HPZIF-8). A mechanistic study of materials synthesis involved an in situ synthesis of zinc hydroxide nitrate nanosheets with an interplanar distance of 0.97 nm. Terephthalic acid modulates the pH value of the synthesis solution leading to the formation of HPZIF-8 with the Brunauer-Emmett-Teller (BET) surface area, Langmuir surface area, and total pore size of 1442 m2 g-1, 1900 m2 g-1, and 0.69 cm3 g-1, respectively. The formed phases during the synthesis undergo fast conversion to HPZIFs at room temperature. The application of the prepared materials in the hydrolysis of NaBH4 is reported. Acidity plays an important role in the catalytic performance of the materials. ZIF-8 prepared using terephthalic acid shows high catalytic activity with a hydrogen rate of 2333 mLH2 min-1 gcat-1 (8046 mLH2 min-1 gZn-1). The material exhibits high catalytic activity without any deterioration of its performance for several uses during continuous NaBH4 feeding. There are no changes in the material's structure after catalysis indicating the high recyclability of the materials.


[Development of Mycobacterium lacticolum and its synthesis of exopolysaccharide under conditions of varying acidity of the medium].
Mycobacterium lacticolum 121 grows and synthesizes exopolysaccharide at the initial values of pH of the medium from 5.0 to 11.5. The accumulation of biomass is maximal (10 to 12 gram/litre) at pH 6.0 to 11.5; the rate of growth is highest at pH 8.0 to 11.5. The largest amount of exopolysaccharide (2.0 to 2.4 gram/litre) is produced in the medium at pH 8.0 to 11.0; the rate of its production is highest at pH 9.0 to 11.0. The growth of Mycobacterium lacticolum 121 and the biosynthesis of polysaccharide are optimal at pH 8.0 to 8.2. Changes in acidity of the medium have no effect on the qualitative composition, structure, and molecular weight of the polysaccharide.


Modeling of time-dependent safety performance using anonymized and aggregated smartphone-based dangerous driving event data.
Safety performance functions (SPFs) are generally used to relate exposure to the expected number of crashes aggregated over a long time (e.g. a year) by holding all other risk factors constant, and to identify hotspots that have excessive crashes regardless of different time periods. However, it is highly likely that the relationships of exposure, risk factors and crash occurrence can vary across different times of day. This study aims to establish time-dependent SPFs for urban roads by using large-scale dangerous driving event data captured by smartphones in different times of day. Multivariate conditional autoregressive (MVCAR) models are developed to jointly account for spatial and temporal dependence of crash observations. Results of two-sample Kolmogorov-Smirnov tests affirm the heterogeneity of the safety effects of dangerous driving events in different time periods. Time-dependent hotspots are identified using potential for safety improvement (PSI) metric. The assumption here is that due to the change of traffic conditions and environment across different times of day, safety hotspots for different time periods should be different from each other. According to the results of Wilcoxon signed-rank tests, hotspots identified by times of day are found to be mostly different from each other. The findings of this study provide insights into temporal effects of risk factors and can support the development of time-dependent safety countermeasures. Besides, this study also shows the potential of leveraging anonymized and aggregated dangerous driving data to assess traffic safety issues.


Preparing Developing Peripheral Olfactory Tissue for Molecular and Immunohistochemical Analysis in Drosophila.
The olfactory system of Drosophila is a widely used system in developmental neurobiology, systems neuroscience, as well as neurophysiology, behavior, and behavioral evolution. Drosophila olfactory tissues house the olfactory receptor neurons (ORNs) that detect volatile chemical cues in addition to hydro- and thermo-sensory neurons. In this protocol, we describe the dissection of developing peripheral olfactory tissue of the adult Drosophila species. We first describe how to stage and age Drosophila larvae, followed by the dissection of the antennal disc from early pupal stages, followed by the dissection of the antennae from mid-pupal stages and adults. We also show methods where preparations can be utilized in molecular techniques, such as the RNA extraction for qRT-PCR, RNAseq, or immunohistochemistry. These methods can also be applied to other Drosophila species after species-specific pupal development times are determined, and respective stages are calculated for appropriate aging.


Acute stress does not impair long-term memory retrieval in older people.
Previous studies have shown that stress-induced cortisol increases impair memory retrieval in young people. This effect has not been studied in older people; however, some findings suggest that age-related changes in the brain can affect the relationships between acute stress, cortisol and memory in older people. Our aim was to investigate the effects of acute stress on long-term memory retrieval in healthy older people. To this end, 76 participants from 56 to 76 years old (38 men and 38 women) were exposed to an acute psychosocial stressor or a control task. After the stress/control task, the recall of pictures, words and stories learned the previous day was assessed. There were no differences in memory retrieval between the stress and control groups on any of the memory tasks. In addition, stress-induced cortisol response was not associated with memory retrieval. An age-related decrease in cortisol receptors and functional changes in the amygdala and hippocampus could underlie the differences observed between the results from this study and those found in studies performed with young people.


[Immune state in athletes with mitral valve prolapse].
The authors evaluated immune state in 541 professional athletes. The athletes with vitral valve prolapse (132 subjects) appeared to have immune changes - lower immunoglobulines levels, general leucocytes count, if compared to the athletes without mitral valve prolapse.


Transcriptional regulation of Salmonella enterica virulence plasmid genes in cultured macrophages.
The plasmid-carried spv genes promote virulence of salmonellae in mice by allowing bacterial growth in the reticuloendothelial tissue. When the bacteria are cultivated under normal laboratory conditions the spv genes appear dormant. This communication explores the transcriptional regulation of spv genes within murine macrophage-like J774-A.1 cells utilizing a new reporter system. Transcriptional fusions were constructed between promoter elements of the Salmonella enterica var. Typhimurium spv genes and the KS71A fimbrial gene cluster. The expression of KS71A fimbriae in fusion-carrying Escherichia coli strains was found to be under the control of the transcriptional activator gene spvR. In strains overproducing SpvR, KS71A fimbriae were assembled on the bacterial cell surface and could be detected by bacterial agglutination or immunofluorescence of intact bacteria; the reporter activity was quantified by estimating the percentage of fluorescent bacteria and by immunoblotting of cell lysates. The activity of the reporters, when transformed into the parent Typhimurium TML R66, was low and revealed less than 0.3% fimbriated cells under in vitro culture conditions. A 15-30-fold increase in fimbriation was observed when the bacteria were cultivated within J774-A.1 cells. No such increase occurred when the reporter fusions were transformed into TML R66 cured of the virulence plasmid. Insertional inactivation of the spvR gene of the virulence plasmid in Typhimurium TML R66 also abolished induction, whereas corresponding inactivation of spvA or spvB did not reduce induction. No increase in reporter activity was obtained in Typhimurium of line Q1, which is naturally avirulent for mice, although the strain was provided with virulence plasmid pEX102 of line TML R66. We conclude that the intracellular environment of J774-A.1 cells induces the spv genes and that this induction requires gene functions of both the bacterial chromosome and the virulence plasmid.


Arteriolar oxygen reactivity: where is the sensor?
The hypothesis that arterioles are intrinsically sensitive to oxygen was tested by comparing arteriolar diameter responses with local and global PO2 changes in superfused hamster cheek pouch preparations. Local PO2 changes were produced by microapplication of fluid onto the surface of occluded or unoccluded aparenchymal arterioles or by cannulation and perfusion of arterioles in situ. Global changes refer to PO2 changes in the superfusate flowing over the entire preparation. Local, effective PO2 changes had no significant effect on arteriolar diameters. In contrast, global PO2 changes produced significant, reproducible changes in diameter. These observations do not support the hypothesis that arterioles are intrinsically oxygen sensitive, unless the oxygen-sensitive sites are distributed sparsely along the arteriolar tree. The data are consistent with oxygen sensors located either in vessels downstream from 15-micron arterioles (in terminal arterioles, capillaries, or venules) or in the parenchyma. The data also suggest that these sensors detect changes in PO2 and then initiate responses that can be conducted along the vasculature to an arteriole distant from the sensor.


A cluster randomised controlled trial of patient-held medical records for people with schizophrenia receiving shared care.
Patient-held records can improve communication across the primary-secondary interface. There has been no previous rigorous assessment of the utility of patient-held records for people with schizophrenia from a primary care perspective and their value for this population is unclear. To evaluate the effectiveness of a patient-held record for patients with schizophrenia receiving shared care. Cluster randomised controlled trial. Seventy-four general practices and six community mental health localities in Birmingham, England between June 1998 and June 1999. A sample of 201 patients with schizophrenia (ICD-10 classification F20) was recruited; of these, 100 were intervention and 101 were control. Patient-held records were given to the intervention patients. At 12-month follow-up, all patients were accounted for and 191 (95%) were revisited. Primary outcomes were the Verona Service Satisfaction Scale-54 (VSSS-54) and the Krawiecka and Goldberg (K & G) rating scale of psychopathology at 12-month follow-up. Secondary outcomes were use of primary and secondary care services. A total of 63/92 (68.5%) patients still had the patient-held record, 64/92 (69.6%) had used it, and 39 (60.9%) of the 64 who had used it said the patient-held record was regularly used by their keyworker. However the patient-held record had no significant effect on primary outcomes (VSSS-54: F1,116 = 0.06, P = 0.801, K & G: F1,116 = 0.6, P = 0.439) or on use of services. A higher symptom score was associated with not using the patient-held record. The trial provides no good evidence to suggest that patient-held records should be introduced as part of routine shared care for all patients with schizophrenia. However, the patient-held record was acceptable to patients with schizophrenia and acted as a communication tool, particularly between patients and keyworkers.


Perinatal care in SARS-CoV-2 infected women: the lesson learnt from a national prospective cohort study during the pandemic in Italy.
Despite the growing importance given to ensuring high-quality childbirth, perinatal good practices have been rapidly disrupted by SARS-CoV-2 pandemic. This study aimed at describing the childbirth care provided to infected women during two years of COVID-19 emergency in Italy. A prospective cohort study enrolling all women who gave birth with a confirmed SARS-CoV-2 infection within 7 days from hospital admission in the 218 maternity units active in Italy during the periods February 25, 2020-June 30, 2021, and January 1-May 31, 2022. Perinatal care was assessed by evaluating the prevalence of the following indicators during the pandemic: presence of a labour companion; skin-to-skin; no mother-child separation at birth; rooming-in; breastfeeding. Logistic regression models including women' socio-demographic, obstetric and medical characteristics, were used to assess the association between the adherence to perinatal practices and different pandemic phases. During the study period, 5,360 SARS-CoV-2 positive women were enrolled. Overall, among those who had a vaginal delivery (n = 3,574; 66.8%), 37.5% had a labour companion, 70.5% of newborns were not separated from their mothers at birth, 88.1% were roomed-in, and 88.0% breastfed. These four indicators showed similar variations in the study period with a negative peak between September 2020 and January 2021 and a gradual increase during the Alpha and Omicron waves. Skin-to-skin (mean value 66.2%) had its lowest level at the beginning of the pandemic and gradually increased throughout the study period. Among women who had a caesarean section (n = 1,777; 33.2%), all the indicators showed notably worse outcomes with similar variations in the study period. Multiple logistic regression analyses confirm the observed variations during the pandemic and show a lower adherence to good practices in southern regions and in maternity units with a higher annual number of births. Despite the rising trend in the studied indicators, we observed concerning substandard childbirth care during the SARS-CoV-2 pandemic. Continued efforts are necessary to underscore the significance of the experience of care as a vital component in enhancing the quality of family-centred care policies.


An ancient conserved role for prion protein in learning and memory.
The misfolding of cellular prion protein (PrPC) to form PrP Scrapie (PrPSc) is an exemplar of toxic gain-of-function mechanisms inducing propagated protein misfolding and progressive devastating neurodegeneration. Despite this, PrPC function in the brain is also reduced and subverted during prion disease progression; thus understanding the normal function of PrPC in healthy brains is key. Disrupting PrPC in mice has led to a myriad of controversial functions that sometimes map onto disease symptoms, including a proposed role in memory or learning. Intriguingly, PrPC interaction with amyloid beta (Aβ) oligomers at synapses has also linked its function to Alzheimer's disease and dementia in recent years. We set out to test the involvement of PrPC in memory using a disparate animal model, the zebrafish. Here we document an age-dependent memory decline in prp2-/- zebrafish, pointing to a conserved and ancient role of PrPC in memory. Specifically, we found that aged (3-year-old) prp2-/- fish performed poorly in an object recognition task relative to age-matched prp2+/+ fish or 1-year-old prp2-/- fish. Further, using a novel object approach (NOA) test, we found that aged (3-year-old) prp2-/- fish approached the novel object more than either age-matched prp2+/+ fish or 1-year-old prp2-/- fish, but did not have decreased anxiety when we tested them in a novel tank diving test. Taken together, the results of the NOA and novel tank diving tests suggest an altered cognitive appraisal of the novel object in the 3-year-old prp2-/- fish. The learning paradigm established here enables a path forward to study PrPC interactions of relevance to Alzheimer's disease and prion diseases, and to screen for candidate therapeutics for these diseases. The findings underpin a need to consider the relative contributions of loss- versus gain-of-function of PrPC during Alzheimer's and prion diseases, and have implications upon the prospects of several promising therapeutic strategies.


Integration of pharmacotherapy and psychosocial treatment in opiate-addicted youth.
Misuse of prescription opioids, particularly by adolescents, is a growing problem in the United States. It is a leading cause of death and disability in this age group. The primary form of treatment available to adolescents is drug free psychosocial programs. For the high risk group that has relapsed after traditional psychosocial treatment, pharmacotherapy needs to be explored. Two primary issues need to be addressed: the development of effective treatment, including the use of opiate antagonists and ongoing monitoring, and education and training of clinicians regarding appropriate prescribing practices in pain management, with better identification of those who misprescribe for personal gain.


Protective effects of coenzyme Q10 and L-carnitine against statin-induced pancreatic mitochondrial toxicity in rats.
Statins are widely used in patients with hyperlipidemia and whom with high risk of cardiovascular diseases. Unfortunately, statins also exert some adverse effects on the liver and pancreas and enhance the risk of type 2 diabetes mellitus. The objective of the present research was to investigate the protective effects of coenzyme Q10 (Co-Q10) and L-carnitine (LC) on statins induced toxicity on pancreatic mitochondria in vivo. Seven groups of male Wistar rats received atorvastatin (20 mg/kg, p.o.), atorvastatin + Co-Q10 (10 mg/kg, i.p.), atorvastatin + LC (500 mg/kg, i.p.), lovastatin (80 mg/kg, p.o), lovastatin + Co-Q10 (10 mg/kg, i.p.), and lovastatin + LC (500 mg/kg, i.p.). Serum glucose and insulin levels were measured before and after two weeks of treatment, while the pancreas was removed and toxic effects of statins, as well as the protective effects of Co-Q10 and LC were assessed. The results showed that atorvastatin and lovastatin significantly increased glucose level and decreased insulin secretion. The glucose level in Co-Q10 and LC groups was significantly lower than statins alone groups. The findings also showed that statin groups had higher rate of pancreatic toxicity including higher level of reactive oxygen species production, decreased cytochrome c oxidase activity, collapse of mitochondrial membrane potential and swelling in comparison to controls. These factors were significantly diminished by co-administration of Co-Q10 or LC compared to statin groups alone. Additionally, supplements caused a significant increase in serum insulin and succinate dehydrogenase activity. Our study provided new evidence supporting beneficial effects of Co-Q10 and LC on statin-induced pancreatic toxicity.


Effect of platelet calpain on normal T-lymphocyte CD43: hypothesis of events in the Wiskott-Aldrich syndrome.
The Wiskott-Aldrich syndrome (WAS) is an inherited disease involving defects of platelets (small size, severe thrombocytopenia due to accelerated destruction) and T lymphocytes (progressive immunodeficiency, lymphopenia). The best-characterized molecular defect is the deficiency and, in some cases, abnormal forms of the T-lymphocyte surface mucin molecule CD43; deficiency of the platelet surface mucin GPIb was observed previously in two of four patients. Neither of these defects is primary, since CD43 and GPIb are encoded by autosomal genes and the disease is X-linked. This study uses cellular biological approaches to explore the possibility that destruction of structurally defective WAS platelets, mimicked experimentally by sonication of normal platelets, plays a role by releasing protease and generating other cellular defects. We show that a protease of normal platelets, identified as Ca(2+)-dependent neutral protease (calpain), which is known to cleave platelet GPIb, also specifically cleaves CD43 on the surface of neighboring desialylated T lymphocytes. The identification of the CD43 cleaving protease was based on its requirement for Ca2+ and inhibition by leupeptin, but not by diisopropylfluorophosphate (DFP). The approximate site of CD43 cleavage was identified by the use of a rabbit antibody. Sensitivity of GPIb to calpain is shown to be sialylation-independent and that of CD43 to be sialylation-dependent, and these findings are explained in terms of molecular structures. These and previous findings are incorporated into a putative mechanism, which explains most of the defects in the WAS. The mechanism suggests that the primary defective molecule in the WAS is unlikely to be a surface glycoprotein, but rather a cytoplasmic molecule with a function in cytoskeletal interactions and/or calcium ion regulation and calpain activation.


Analysis of membrane protein self-association in lipid systems by fluorescence particle counting: application to the dihydropyridine receptor.
Fluorescence particle counting (FPC) is employed to analyze the distribution of a purified membrane protein, the dihydropyridine receptor (DHP-R), in detergent micelles, in lipid vesicles, and in lipid monolayers generated from the vesicles. The method was used to identify conditions for which DHP-Rs occur singly distributed in micelles and in vesicles. In monolayers, the DHP-R showed self-association, starting from monomeric distribution at concentrations (c) of typically 10 DHP-R/microm2. The average cluster size [m(t)] of associates was followed by FPC in time and the dependence of the lateral diffusion constant [D(lat)(m,pi)] of the associates on the surface pressure (pi) was determined. By studying the dependence of m(t) on c, pi, D(lat)(pi), and salt concentration (c(s)), we derived an empirical expression for the association rate constant (k(a)) and for m(t) that fits the experimental m(t) relations. Theoretical justification for these dependencies is obtained from collision theory, leading to a mechanistic picture of the aggregation process. DHP-R association is irreversible. Its rate is not diffusion-limited. A large number of collisions is required to overcome an interaction energy barrier of about 6-11 kT, depending on m and c(s) but not on pi. The increase in association rate with increasing average cluster size m is related to increasing van der Waals attraction, while the increase in rate with increasing c(s) relates to decreasing electrostatic repulsion. Van der Waals and electrostatic forces represent, however, only part of the interaction energy. The main contribution was not dependent on the variables studied and, most likely, reflects hydration forces which need to be overcome for association.


Acute and late neurotoxicity in the rat spinal cord in vivo induced by glutamate receptor agonists.
We investigated glutamate receptor-mediated neurotoxicity in vivo by means of infusing three specific agonists for non-NMDA receptors (acromelic acid A (ACRO), kainic acid and 1-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)) into the adult rat spinal subarachnoid space. ACRO induced long-lasting pure motor, rigid-spastic paraparesis in a dose-dependent manner (EC50: 220 pmol/h) that was accompanied by selective degeneration of spinal interneurons; leaving large anterior horn cells intact. Kainate and AMPA induced paraplegia but with relatively non-selective neuronal damage when given in doses more than 40-fold larger than those required for ACRO. When AMPA (> 100 nmol/h) was infused continuously using a mini-osmotic pump for more than 2 days, rats displayed progressive changes in motor behavior due to extensive damage in the caudal spinal cord where small neurons in the dorsal horns were the most vulnerable. Co-administration of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) specifically prevented neurotoxicity, suggesting a non-NMDA receptor-mediated mechanism. These results indicate that the non-NMDA receptor is heterogeneous, mediating neuronal damage with different selectivity. It is also suggested that chronic activation of glutamate receptors is capable of inducing slowly progressive neuronal death, which suggests relevance to the pathogenesis of ALS.


[Magnetic resonance tomography of the shoulder. Possibilities of over interpretation of normal findings].
In order to test the criteria for abnormalities of the shoulder as seen on MR, 30 normal shoulders were examined. The examination included T1, proton and T2-weighted SE sequences and T2*-weighted FE sequences, using transverse, oblique coronary and oblique sagittal planes. In 57% there was increased signal intensity in the tendon of the rotator cuff; this might have been interpreted as a rupture of the cuff or tendinitis. Anatomical examination suggests that the finding is due to a normal layer between the long head of the biceps and the tendon joint complex. The anterior glenoid labrum could not be clearly delineated in 57% and the posterior labrum in 5%. In two cases there was a superior, postero-lateral defect in the head of the humerus. The currently accepted criteria for the MRT diagnosis of shoulder abnormalities need to be critically re-evaluated.


[The expression of the apolipoprotein A-1 gene in the early stages of human embryogenesis studied by hybridization in situ].
The apolipoprotein A-1 (apo A-1) gene expression at certain stages of human embryo development was studied using an in situ hybridization procedure. By the fifth week of development, the presence of apo A-1 mRNAs was detected in cells of different tissue types such as CNS rudiment, somite myotomes, ear vesicle, nasal placodes, lens, apical areas of the maxillary, mandibular and hyoid arcs, mesenchyme of limb buds, small intestine, mesonephros, genital ridge, and several types of blood cells. At later stages (weeks 8-9) the distribution of these mRNAs showed considerable changes. The high apo A-1 mRNA level was characteristic of liver cells, adrenals, kidney, neural tube and ganglia. These data suggest that changes in tissue-specific apo A-1 gene expression during human embryogenesis may be associated with the development of blood circulatory system and CNS.


Wickerhamomyces siamensis sp. nov., a novel yeast species isolated from the phylloplane in Thailand.
Strain DMKU-RK359(T), representing a novel yeast species, was isolated from the external surface of a sugar-cane leaf collected in Thailand. On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics, sequence analysis of the D1/D2 region of the large-subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, strain DMKU-RK359(T) was assigned to a novel Wickerhamomyces species. The novel species was closest to Wickerhamomyces ciferrii, but differed from it by 0.7 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene and 6 % nucleotide substitutions in the ITS region. The name Wickerhamomyces siamensis sp. nov. is proposed (type strain DMKU-RK359(T) = BCC 50732(T) = NBRC 108900(T) = CBS 12570(T)).


Neuron-specific impairment of inter-chromosomal pairing and transcription in a novel model of human 15q-duplication syndrome.
Although the etiology of autism remains largely unknown, cytogenetic and genetic studies have implicated maternal copy number gains of 15q11-q13 in 1-3% of autism cases. In order to understand how maternal 15q duplication leads to dysregulation of gene expression and altered chromatin interactions, we used microcell-mediated chromosome transfer to generate a novel maternal 15q duplication model in a human neuronal cell line. Our 15q duplication neuronal model revealed that by quantitative RT-PCR, transcript levels of NDN, SNRPN, GABRB3 and CHRNA7 were reduced compared with expected levels despite having no detectable alteration in promoter DNA methylation. Since 15q11-q13 alleles have been previously shown to exhibit homologous pairing in mature human neurons, we assessed homologous pairing of 15q11-q13 by fluorescence in situ hybridization. Homologous pairing of 15q11-q13 was significantly disrupted by 15q duplication. To further understand the extent and mechanism of 15q11-q13 homologous pairing, we mapped the minimal region of homologous pairing to a ∼500 kb region at the 3' end of GABRB3 which contains multiple binding sites for chromatin regulators MeCP2 and CTCF. Both active transcription and the chromatin factors MeCP2 and CTCF are required for the homologous pairing of 15q11-q13 during neuronal maturational differentiation. These data support a model where 15q11-q13 genes are regulated epigenetically at the level of both inter- and intra-chromosomal associations and that chromosome imbalance disrupts the epigenetic regulation of genes in 15q11-q13.


An official American Thoracic Society Clinical Practice Guideline: sleep apnea, sleepiness, and driving risk in noncommercial drivers. An update of a 1994 Statement.
Sleepiness may account for up to 20% of crashes on monotonous roads, especially highways. Obstructive sleep apnea (OSA) is the most common medical disorder that causes excessive daytime sleepiness, increasing the risk for drowsy driving two to three times. The purpose of these guidelines is to update the 1994 American Thoracic Society Statement that described the relationships among sleepiness, sleep apnea, and driving risk. A multidisciplinary panel was convened to develop evidence-based clinical practice guidelines for the management of sleepy driving due to OSA. Pragmatic systematic reviews were performed, and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to formulate and grade the recommendations. Critical outcomes included crash-related mortality and real crashes, whereas important outcomes included near-miss crashes and driving performance. A strong recommendation was made for treatment of confirmed OSA with continuous positive airway pressure to reduce driving risk, rather than no treatment, which was supported by moderate-quality evidence. Weak recommendations were made for expeditious diagnostic evaluation and initiation of treatment and against the use of stimulant medications or empiric continuous positive airway pressure to reduce driving risk. The weak recommendations were supported by very low-quality evidence. Additional suggestions included routinely determining the driving risk, inquiring about additional causes of sleepiness, educating patients about the risks of excessive sleepiness, and encouraging clinicians to become familiar with relevant laws. The recommendations presented in this guideline are based on the current evidence, and will require an update as new evidence and/or technologies becomes available.


Evaluation of conductive cooling of lactating dairy cows under controlled environmental conditions.
Cooling systems used to reduce heat stress in dairy operations require high energy, water usage, or both. Steady increases in electricity costs and reduction of water availability and an increase in water usage regulations require evaluation of passive cooling systems to cool cows and reduce use of water and electricity. A study was conducted to evaluate the use of heat exchangers buried 25 cm below the surface as components in a conductive system for cooling cows. Six cows were housed in environmentally controlled rooms with tie-stall beds, which were equipped with a heat exchanger and filled with 25 cm of either sand or dried manure. Beds were connected to supply and return lines and individually controlled. Two beds (one per each kind of bedding material) constituted a control group (water off), and the other 4 (2 sand and 2 dried manure) used water at 7°C passing through the heat exchangers (water on). The experiment was divided in 2 periods of 40 d, and each period involved 3 repetitions of 3 different climates (hot and dry, thermo neutral, and hot and humid). Each cow was randomly assigned to a different treatment after each repetition was over. Sand bedding remained cooler than dried manure bedding in all environments and at all levels of cooling (water on or off). Bed temperatures were lower and heat flux higher during the bed treatment with sand and water on. We also detected a reduction in core body temperatures, respiration rates, rectal temperatures, and skin temperatures of those cows during the sand and water on treatment. Feed intake and milk yield numerically increased during the bed treatment with sand and water on for all climates. No major changes were observed in the lying time of cows or the composition of the milk produced. We conclude that use of heat exchangers is a viable adjunct to systems that employ fans, misters, and evaporative cooling methods to mitigate effects of heat stress on dairy cows. Sand was superior to dried manure as a bedding material in combination with heat exchangers.


Electromechanical phase transition in hexacyanometallate nanostructure (Prussian Blue).
This paper demonstrates the importance of the structural changeover in controlling the physical-chemical properties of hexacyanometalate-like materials (Prussian Blue). A meticulous in situ study of compositional variations using electroacoustic impedance techniques associated to electrogravimetric techniques in hexacyanoferrates containing K+ alkali metals reveals the existence of a nanostructural changeover coupled to a change of the magnetic properties of these electromagnetic materials. In the same way, the electroacoustic impedance techniques can be useful both in the understanding and in the in situ monitoring of the structural changeovers and the magnetic behavior of all kinds of materials.


Live Multiattribute Data Mining and Penalty Decision-Making in Basketball Games Based on the Apriori Algorithm.
The Apriori algorithm is used to conduct an in-depth analysis and research on the relationship between data mining and penalty decision of multiattribute data in the basketball game scene. The technical and tactical features are analyzed using an improved Apriori algorithm for association rule analysis of basketball game data. The algorithm generates association rules based on mining the set of frequent items among basketball technical actions. The improved algorithm can mine the technical moves that are more connected in the game data, and the analysis results are highly instructive. The technical and tactical directed analysis is divided into two parts: technical and tactical directed action analysis and technical and tactical directed cooperation analysis. The key action analysis uses Markov process-based data mining algorithm to analyze the basketball game data for key score transfer steps and key score loss transfer steps. The algorithm can find the key actions of scoring and key actions of conceding points in the game process, and the analysis results can guide basketball training and games, which has high practical value. Using the collated game data as the independent variable and the number of games won and lost as the dependent variable, logistic regression analysis is applied to derive the characteristics that affect winning. Again, the decision tree algorithm is used to select the significant features that affect winning and to make predictions of team performance. Finally, the technical statistics of the main players in the last three seasons are selected, and the association rule algorithm is applied to derive the degree of influence of player performance on the outcome of the game.


Identification of Novel Endogenous Controls for qPCR Normalization in SK-BR-3 Breast Cancer Cell Line.
Normalization of gene expression using internal controls or reference genes (RGs) has been the method of choice for standardizing the technical variations in reverse transcription quantitative polymerase chain reactions (RT-qPCR). Conventionally, ACTB and GAPDH have been used as reference genes despite evidence from literature discouraging their use. Hence, in the present study we identified and investigated novel reference genes in SK-BR-3, an HER2-enriched breast cancer cell line. Transcriptomic data of 82 HER2-E breast cancer samples from TCGA database were analyzed to identify twelve novel genes with stable expression. Additionally, thirteen RGs from the literature were analyzed. The expression variations of the candidate genes were studied over five successive passages (p) in two parallel cultures S1 and S2 and in acute and chronic hypoxia using various algorithms. Finally, the most stable RGs were selected and validated for normalization of the expression of three genes of interest (GOIs) in normoxia and hypoxia. Our results indicate that HSP90AB1, DAD1, PFN1 and PUM1 can be used in any combination of three (triplets) for optimizing intra- and inter-assay gene expression differences in the SK-BR-3 cell line. Additionally, we discourage the use of conventional RGs (ACTB, GAPDH, RPL13A, RNA18S and RNA28S) as internal controls for RT-qPCR in SK-BR-3 cell line.


[Lipid content of mitochondrial membranes of the rat liver in alloxan diabetes].
Lipid content of liver mitochondrial membranes was studied in rats with alloxan diabetes. It was shown that the concentration of mitochondrial neutral lipids rose, whereas phospholipid content in the external membrane descended and that in the internal membrane ascended. The level of mitochondrial phospholipid saturated fatty acids tended toward increase. Phospholipid-composing phosphatidylserine and cardiolipin underwent the greatest changes. It is suggested that in alloxan diabetes, the mitochondrial membrane becomes more rigid at the expense of high cholesterol and saturated fatty acid concentrations. The changes in phospholipid content seem to be due to endogenous phospholipase activation.


Contribution of EXT1, EXT2, and EXTL3 to heparan sulfate chain elongation.
The exostosin (EXT) family of genes encodes glycosyltransferases involved in heparan sulfate biosynthesis. Five human members of this family have been cloned to date: EXT1, EXT2, EXTL1, EXTL2, and EXTL3. EXT1 and EXT2 are believed to form a Golgi-located hetero-oligomeric complex that catalyzes the chain elongation step in heparan sulfate biosynthesis, whereas the EXTL proteins exhibit overlapping glycosyl-transferase activities in vitro, so that it is not apparent what reactions they catalyze in vivo. We used gene-silencing strategies to investigate the roles of EXT1, EXT2, and EXTL3 in heparan sulfate chain elongation. Small interfering RNAs (siRNAs) directed against the human EXT1, EXT2, or EXTL3 mRNAs were introduced into human embryonic kidney 293 cells. Compared with cells transfected with control siRNA, those transfected with EXT1 or EXT2 siRNA synthesized shorter heparan sulfate chains, and those transfected with EXTL3 siRNA synthesized longer chains. We also generated human cell lines overexpressing the EXT proteins. Overexpression of EXT1 resulted in increased HS chain length, which was even more pronounced in cells coexpressing EXT2, whereas overexpression of EXT2 alone had no detectable effect on heparan sulfate chain elongation. Mutations in either EXT1 or EXT2 are associated with hereditary multiple exostoses, a human disorder characterized by the formation of cartilage-capped bony outgrowths at the epiphyseal growth plates. To further investigate the role of EXT2, we generated human cell lines overexpressing mutant EXT2. One of the mutations, EXT2-Y419X, resulted in a truncated protein. Interestingly, the capacity of wild type EXT2 to enhance HS chain length together with EXT1 was not shared by the EXT2-Y419X mutant.


Multiplex reverse transcription polymerase chain reaction assessment of sialyltransferase expression in human breast cancer.
Increased sialylation, especially involving the Sialyl-Lewisa and Sialyl-Lewisx determinants, has been reported in breast cancer. A multiplex reverse transcription-PCR method was used here to determine the expression of five sialyltransferases (ST3Gal III, ST6Gal I, ST3Gal IV, ST3Gal I, and ST3Gal II) in 49 patients surgically treated for locoregional breast cancer. We assessed the relationship between these expressions and clinical, pathological, and biological features. The most expressed sialyltransferase was ST3Gal 1II, which is involved in Sialyl-Lewisa synthesis. ST3Gal III expression was positively correlated to ST6Gal I and ST3Gal IV expressions, to tumor size, and to the number of involved axillary nodes. Patients with high ST3Gal III expression had a shorter overall survival. High ST6Gal I expression was associated with histoprognostic grade III. ST6Gal I expression was negatively correlated to expression of progesterone receptor. In conclusion, high ST3Gal III and ST6Gal I expressions in human breast tumors are associated with poor prognosis markers.


Nucleotide sequence, mutational analysis, transcriptional start site, and product analysis of nov, the gene which affects Escherichia coli K-12 resistance to the gyrase inhibitor novobiocin.
In a previous study, we demonstrated the existence of a gene locus, nov, which affects resistance of Escherichia coli K-12 to the gyrase inhibitor novobiocin and, to a lesser degree, coumermycin (J. Rakonjac, M. Milic, D. Ajdic, D. Santos, R. Ivanisevic, and D. J. Savic, Mol. Microbiol. 6:1547-1553, 1992). In the present study, sequencing of the nov gene locus revealed one open reading frame that encodes a protein of 54,574 Da, a value. found to be in correspondence with the size of the Nov protein identified in an in vitro translation system. We also located the 5' end of the nov transcript 8 bp downstream from a classical sigma70 promoter. Transcription of the gene is in the counterclockwise direction on the E. coli chromosome. Transposon mutagenesis of nov followed by complementation analyses and replacement of chromosomal alleles with mutated nov confirmed our previous assumption that the nov gene exists in two allelic forms and that the Novr gene is an active allele while the Novs gene is an inactive form. After comparing nucleotide sequences flanking the nov gene with existing data, we conclude that the gene order in this region of the E. coli K-12 map is att phi 80-open reading frame of unknown function-kch (potassium channel protein)-nov-opp. Finally, the possible identity of the nov gene with cls, the gene that codes for cardiolipin synthase, is also discussed.


Arm use after left or right hemiparesis is influenced by hand preference.
Despite strong evidence for hand preference and its impact on motor performance, its influence on stroke rehabilitation has not been routinely considered. Previous research demonstrates that patients with hemiparetic stroke use their ipsilesional, nonparetic arm 5 to 6 times more frequently than their paretic arm, but it is unknown if such use varies with laterality of hemiparesis. The purpose of our study was to determine if the right arm is used more frequently in right-handed patients with stroke. We assessed relative use of the right, left, and both arms with wrist accelerometers on patients with unilateral, paretic stroke matched for degree of paresis (12 with right hemisphere damage, 17 with left hemisphere damage) and 25 neurologically intact control participants as they performed the Arm Motor Ability Test. We showed: (1) ipsilesional arm use was greater after right hemisphere damage than left hemisphere damage; (2) the left hemisphere damage group used both arms together more often than the right hemisphere damage group but less often than the control group; and (3) both stroke groups used their contralesional, paretic arm to the same degree. These findings emphasize the influence of hand preference on arm use after stroke for the ipsilesional but not the contralesional arm. Although both stroke groups used their ipsilesional more than their contralesional arm, the difference was greater for the right hemisphere damage group who used their ipsilesional arm 4 times more frequently than their contralesional arm, whereas the left hemisphere damage group used their ipsilesional arm 2 times more frequently than their contralesional arm.


Inhibition of angiotensin-converting enzyme for diagnosis of renal-artery stenosis.
To determine its utility as an aid in diagnosis of renovascular hypertension, we administered nonapeptide converting-enzyme inhibitor (CEI) (which inhibits conversion of angiotensin I to angiotensin II) (0.25 mg per kilogram) to 14 unselected hypertensive patients undergoing bilateral renal-vein catheterization. In seven (Group I) predominantly unilateral disease was discovered by angiography (renal-artery stenosis in six and hydronephrosis in one); in the remaining seven (Group II) no rennal-artery abnormality was found. In Group I, mean (+/- S.E.) ratio of involved to uninvolved renal-vein plasma renin activity (PRA) increased from 2.94 +/- 0.91 before to 8.36 +/- 2.94 after CEI (P less than 0.01). In Group II, the ratio (of the initially higher to the lower side) was 1.99 +/- 0.49 before and 1.17 +/- 0.07 after CEI (P greater 0.02). Post-CEI PRA was predicted by pretreatment PRA. Mean blood pressure fell in both groups after CEI, and the decrement was predicted by pre-CEI PRA. These data suggest that CEI can be of use at the time of renal-vein catheterization, serving to increase diagnostic accuracy by increasing the difference in PRA between the two sides when there is unilateral disease.


Genetic perturbation of the maize methylome.
DNA methylation can play important roles in the regulation of transposable elements and genes. A collection of mutant alleles for 11 maize (Zea mays) genes predicted to play roles in controlling DNA methylation were isolated through forward- or reverse-genetic approaches. Low-coverage whole-genome bisulfite sequencing and high-coverage sequence-capture bisulfite sequencing were applied to mutant lines to determine context- and locus-specific effects of these mutations on DNA methylation profiles. Plants containing mutant alleles for components of the RNA-directed DNA methylation pathway exhibit loss of CHH methylation at many loci as well as CG and CHG methylation at a small number of loci. Plants containing loss-of-function alleles for chromomethylase (CMT) genes exhibit strong genome-wide reductions in CHG methylation and some locus-specific loss of CHH methylation. In an attempt to identify stocks with stronger reductions in DNA methylation levels than provided by single gene mutations, we performed crosses to create double mutants for the maize CMT3 orthologs, Zmet2 and Zmet5, and for the maize DDM1 orthologs, Chr101 and Chr106. While loss-of-function alleles are viable as single gene mutants, the double mutants were not recovered, suggesting that severe perturbations of the maize methylome may have stronger deleterious phenotypic effects than in Arabidopsis thaliana.


Salary discrepancies between practicing male and female physician assistants.
Salary discrepancies between male and female physicians are well documented; however, gender-based salary differences among clinically practicing physician assistants (PAs) have not been studied since 1992 (Willis, 1992). Therefore, the objectives of the current study are to evaluate the presence of salary discrepancies between clinically practicing male and female PAs and to analyze the effect of gender on income and practice characteristics. Using data from the 2009 American Academy of Physician Assistants' (AAPA) Annual Census Survey, we evaluated the salaries of PAs across multiple specialties. Differences between men and women were compared for practice characteristics (specialty, experience, etc) and salary (total pay, base pay, on-call pay, etc) in orthopedic surgery, emergency medicine, and family practice. Men reported working more years as a PA in their current specialty, working more hours per month on-call, providing more direct care to patients, and more funding available from their employers for professional development (p < .001, all comparisons). In addition, men reported a higher total income, base pay, overtime pay, administrative pay, on-call pay, and incentive pay based on productivity and performance (p < .001, all comparisons). Multivariate analysis of covariance and analysis of variance revealed that men reported higher total income (p < .0001) and base pay (p = .001) in orthopedic surgery, higher total income (p = .011) and base pay (p = .005) in emergency medicine, and higher base pay in family practice (p < .001), independent of clinical experience or workload. These results suggest that certain salary discrepancies remain between employed male and female PAs regardless of specialty, experience, or other practice characteristics.


A laser Doppler system for intracerebral measurements during stereotactic neurosurgery.
A laser Doppler system for intracerebral measurements during stereotactic and functional neurosurgery is presented. The system comprises a laser Doppler perfusion monitor, an optical probe adapted for the Leksell Stereotactic System and a personal computer with software for acquisition, data analysis and presentation. The software makes it possible to present both the perfusion and the total backscattered light intensity (TLI) in real-time. During intracerebral measurements, the perfusion signal records the tissue's microcirculation whereas the TLI signal may be used to distinguish between grey and white matter. Evaluation of the system has been done during stereotactic neurosurgery in relation to implantation of deep brain stimulation electrodes. Measurements were made along trajectories towards targets in the deep brain structure as well as in pre-calculated target areas. The measurements show that the system has a potential to be used for intracerebral guidance but further evaluation of the technique is needed.


Spinal block caesarean section in parturients with pregnancy-induced hypertension.
The objective of this work was to determine whether parturients with pregnancy-induced hypertension (PIH) are at higher risk of post-spinal hypotension at caesarean section. This was an observational study of 24 women with PIH undergoing caesarean section under spinal analgesia with 0.5% hyperbaric bupivacaine, compared with 24 matched normotensive parturients receiving a spinal block for caesarean section. The mean intra-operative systolic arterial pressure (SAP) was similar with and without PIH (p = 0.38). The mean percentage decrease in SAP of baseline was more with PIH (16.2%) than in the controls (0.5%) (p < 0.001). The number of episodes of severe hypotension (SAP decrease to < or = 80% of baseline and < 90 mmHg) (p = 0.80) as well as the magnitude (p = 0.31) of severe hypotension was similar in both groups. There was no difference in the evolution of diastolic arterial pressure and maternal pulse rate between cases and controls. Maximum levels of upper sensory blockade were similar. Foetal and maternal outcome was similar with and without PIH. The decrease in SAP is less on an absolute scale but more on a percentile basis with PIH at caesarean section under spinal analgesia than in normotensive patients. The difference, however, is not clinically sufficient to discourage spinal analgesia for caesarean section with a low dose (1.5 ml, 7.5 mg) of 0.5% hyperbaric bupivacaine in parturients with PIH.


Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking.
P-glycoprotein (PgP) is the major drug efflux pump in human cerebral microvessels. PgP prevents pathogens, toxins and therapeutic drugs from entering the CNS. Understanding the molecular regulation of PgP activity will suggest novel mechanisms to improve CNS drug delivery. Previously, we found that during peripheral inflammatory pain (PIP) (3 h after λ carrageenan injection in the rat paw), PgP traffics to the cortical microvessel endothelial cell plasma membrane concomitant with increased PgP activity. In the current study, we measured the changes in composition of PgP-containing protein complexes after PIP in rat microvessel isolates. We found that a portion of the PgP is contained in a multi-protein complex that also contains the caveolar proteins CAV1, SDPR, PTRF and PRKCDBP. With PIP, total CAV1 bound to PgP was unchanged; however, phosphorylated CAV1 (Y14P-CAV1) in the complex increased. There were few PgP/CAV1 complexes relative to total PgP and CAV1 in the microvessels suggesting CAV1 bound to PgP is unlikely to affect total PgP activity. However, both PgP and CAV1 trafficked away from the nucleus in response to PIP. These data suggest that P-CAV1 bound to PgP potentially regulates PgP trafficking and contributes to the acute PgP activity increase after a PIP stimulus.