The human genetic history of Oceania: near and remote views of dispersal.
The human history of Oceania is unique in the way that it encompasses both the first out-of-Africa expansion of modern humans to New Guinea and Australia as well as the last regional human occupation of Polynesia. Other anthropological peculiarities of Oceania include features like the extraordinarily rich linguistic diversity especially of New Guinea with about 1,000 often very distinct languages, the independent and early development of agriculture in the highlands of New Guinea about 10,000 years ago, or the long-term isolation of the entire region from the outside world, which lasted as long as until the 1930s for most of the interior of New Guinea. This review will provide an overview on the genetic aspects of human population history of Oceania and how some of the anthropological peculiarities are reflected in human genetic data. Due to current data availability it will mostly focus on insights from sex-specifically inherited mitochondrial DNA and Y-chromosomal DNA, whereas more genome-wide autosomal DNA data are soon expected to add additional details or may correct views obtained from these two, albeit highly complex, genetic loci.


The discrepancy between echocardiography, cineventriculography and thermodilution. Evaluation of left ventricular volume and ejection fraction.
We have often experienced disagreement in left ventricular end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) between cineventriculography and echocardiography not performed simultaneously, and unnaturally hyperdynamic left ventricular wall motion. We determined EDV, ESV, stroke volume, and EF (with modified Simpson's rule) in 65 consecutive patients using 2-dimensional echocardiography with a 2.5 MHz, 128-element phased-array transducer within three days of cardiac catheterization and compared our results with those obtained by the thermodilution technique and biplane cineventriculography. Heart rate and stroke volume were significantly different among the three techniques: cineventriculography yielded the highest values. These findings suggest that patients may have been in a hyperadrenergic state caused by anxiety experienced during invasive cineventriculography and thermodilution examinations. Inter- and intraobserver variabilities for echocardiography differed little from the variability in cineventriculography. Although there were good correlations between echocardiographic and cineventriculographic findings for EDV (r = 0.67), ESV (r = 0.80), and EF (r = 0.78) by two independent observers, there was a lack of agreement for EDV, ESV, and EF. Echocardiographic EDV values were significantly lower than cineventriculographic values. When left ventricular function is good, the left ventricle tends to be hyperadrenergic and in a more hyperdynamic state with smaller ESV than echocardiographic values during cineventriculography. When left ventricular function is poor, the left ventricle tends to be influenced by the effect of the contrast medium and stress during the invasive examinations and in a more hypodynamic state with larger ESV than echocardiographic values during cineventriculography. The echocardiography is highly reproducible and may provide information that is not available from cineventriculography and thermodilution. Cineventriculography may provide another manifestation of cardiac reserve. In conclusion, we must take into account each peculiar property of the echocardiography, the cineventriculography, or the thermodilution technique when patients are examined with cardiac conditions by different methods at different days.


Caloric restriction results in phospholipid depletion, membrane remodeling, and triacylglycerol accumulation in murine myocardium.
Herein, we utilize the power of shotgun lipidomics to demonstrate that modest caloric restriction results in phospholipid depletion, membrane remodeling, and triacylglycerol (TAG) accumulation in murine myocardium. After brief periods of fasting (4 and 12 h), substantial decreases occurred in the choline and ethanolamine glycerophospholipid pools in murine myocardium (collectively, a decrease of 39 nmol of phospholipid per milligram of protein at 12 h representing approximately 25% of total phospholipid mass and approximately 20 cal of Gibbs free energy per gram wet weight of tissue). Remarkably, the selective loss of long-chain polyunsaturated molecular species was present in the major phospholipid classes thereby altering the physical properties of myocardial membranes. No decrease in TAG mass was present in myocardium during fasting, but rather myocardial TAG increased during 12 h of refeeding nearly 3-fold returning to baseline levels only after 24 h of refeeding. No alterations in other examined lipid classes were present during fasting. In contrast to these lipid alterations in myocardium, no decreases in phospholipid mass were present in skeletal muscle myocytes and a dramatic decrease in skeletal muscle (or skeletal muscle associated) TAG mass was prominent after 12 h of fasting. These results identify phospholipids as a rapidly mobilizable energy source during modest caloric deprivation in murine myocardium, while triacylglycerols are a major source of energy reserve in skeletal muscle. Collectively, these results demonstrate dramatic alterations in the membrane composition of mildly fasted mammalian myocardium that identify the unanticipated plasticity of myocardial phospholipids to adapt to modest chemical and physical perturbations.


Induction of pro-inflammatory programs in enteroendocrine cells by the Toll-like receptor agonists flagellin and bacterial LPS.
Enteroendocrine cells are hormone-secreting cells spread along the intestinal epithelium. Their principal function is to promote the digestion of food. However, little is known about other functions that these cells may play, since they are difficult to study as a whole endocrine organ due to their diffuse localization. It is known that the intestinal epithelial barrier is actively involved in the host defense against pathogen invasion. Here we applied gene expression profiling to characterize the response of the human LCC-18 enteroendocrine cell line to physiological and pathological stimuli mimicked by fatty acids (FAs), flagellin and LPS exposure. We observed that these cells participate in an innate immune reaction to pathogens through the expression of pro-inflammatory factors (i.e. CXCL1 and 3 and IL-32) that we could validate by molecular and proteomic approach. Interestingly, IL-32 has been recently found over-expressed in the inflamed mucosa of patients affected by inflammatory bowel disease. This is very important because modifications of enteroendocrine cells during intestinal inflammation have been so far considered as secondary effects of the inflammatory status rather than due to direct pathogen/enteroendocrine cell interaction. As expected, FAs exposure up-regulates pro-differentiative genes and the production of cholecystokinin but it does not enhance the expression of pro-inflammatory genes. The present observations enlighten a new aspect of the cross talk between immune and endocrine system and suggest enteroendocrine cells as important contributors of inflammatory processes occurring in the gut in response to pathogen exposure and direct enhancers of the inflammatory status associated with human inflammatory bowel disease.


In situ recombination junction between p-Si and TiO2 enables high-efficiency monolithic perovskite/Si tandem cells.
Increasing the power conversion efficiency of silicon (Si) photovoltaics is a key enabler for continued reductions in the cost of solar electricity. Here, we describe a two-terminal perovskite/Si tandem design that increases the Si cell's output in the simplest possible manner: by placing a perovskite cell directly on top of the Si bottom cell. The advantageous omission of a conventional interlayer eliminates both optical losses and processing steps and is enabled by the low contact resistivity attainable between n-type TiO2 and Si, established here using atomic layer deposition. We fabricated proof-of-concept perovskite/Si tandems on both homojunction and passivating contact heterojunction Si cells to demonstrate the broad applicability of the interlayer-free concept. Stabilized efficiencies of 22.9 and 24.1% were obtained for the homojunction and passivating contact heterojunction tandems, respectively, which could be readily improved by reducing optical losses elsewhere in the device. This work highlights the potential of emerging perovskite photovoltaics to enable low-cost, high-efficiency tandem devices through straightforward integration with commercially relevant Si solar cells.


MPTP/MPP+ suppresses activation of protein C in Parkinson's disease.
Endothelial dysfunction and disruption of the blood-brain barrier have been found to be associated with Parkinson's disease (PD). However, the mechanisms underlying these effects have yet to be elucidated. It has also been found that activated protein C (APC) displays neuroprotective properties. Presently, the effects of APC on PD remain unknown. Using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxin rodent model of PD, we found that administration of MPTP can reduce expression of endothelial protein C receptor (EPCR), an N-glycosylated type I membrane protein that has the ability to enhance protein C activation. However, the use of MPTP does not alter levels of thrombomodulin. These findings were verified in an in vitro study showing that 1-methyl-4-phenylpyridinium (MPP+) treatment leads to suppression of EPCR along with reduction of protein C activation in human primary endothelial cells. Importantly, our results display that activation of the transcriptional factor SP1 is involved in the inhibitory effects of MPTP/MPP+ on EPCR expression. We found that using 300 nM of the SP1 inhibitor MIT can abolish the effects of MPP+ on EPCR expression. Consistently, SP1 silencing using small RNA interference was able to prevent the inhibitory effects of MPTP/MPP+ on the reduction of EPCR expression and impairment of protein C activation. Importantly, our results indicate that overexpression of SP1 inhibits EPCR promoter activity. Our study suggests that EPCR-APC may be a potential therapeutic target for endothelial dysfunction in PD.


Oxygen-dependent tension in vascular smooth muscle. Does the endothelium play a role?
We investigated a hypothesis that an oxygen sensor involved in hypoxia-induced relaxation of vascular smooth muscle may reside in endothelial cells. We also determined the oxygen dependence of hypoxia-induced decreases in cyclic guanosine 3',5'-monophosphate concentrations in vascular smooth muscle rings. Rings of canine femoral artery, rabbit thoracic aorta, and lamb ductus arteriosus, either with an intact endothelium or with damaged or absent endothelium, were studied using organ baths that allowed changes in PO2 without a change in pH. Hypoxia-induced relaxations of rabbit thoracic aorta, lamb ductus arteriosus, and canine femoral artery were not dependent on an intact endothelium. The magnitude of hypoxia-induced relaxations was unchanged in rings of canine femoral artery without intact endothelium compared to rings with endothelium. Quasi-steady state organ bath PO2-mechanical tension relationships were unchanged in rings of canine femoral artery without endothelium over an organ PO2 range of 200-20 mm Hg. With rabbit thoracic aorta, magnitudes of hypoxia-induced relaxations were significantly smaller in rings without endothelium. Quasi-steady state plots, where mechanical tension was given as percentage of maximal relaxation, were similar in rings either with or without intact endothelium. Cyclic guanosine 3',5'-monophosphate concentrations were shown to be oxygen-sensitive, decreasing during hypoxia-induced relaxations with a threshold PO2 of 80-100 mm Hg with canine femoral artery, and 60-80 mm Hg with rabbit thoracic aorta rings, but this finding seems unrelated to the mechanism of hypoxia-induced relaxation.


[Importance of catecholamines and various subtypes of beta-adrenoreceptors for resistance of mice to acute, intensive cooling].
A phase dynamics in body temperature and thermoproduction was shown in the course of cooling of mice. 3 periods of various intensity were noted in thermocompensatory reactions. Within the first period content of noradrenaline was maintained in the vitally important tissues (brain, heart and brown adipose tissues); later on the content of noradrenaline was distinctly decreased. The blockade of ganglions and beta-adrenoreceptors inhibited markedly the thermoproduction and resistance to cooling. The main thermocompensatory reactions were realized via beta 1-adrenoreceptors; blocking of beta 1-adrenoreceptors by means of practolol was more effective as compared with the influence of N-isopropylmethoxamine--inhibitor of beta 2-adrenoreceptors. Importance of beta 1-adrenoreceptors in thermoregulation is discussed.


Multicellular Transcriptional Analysis of Mammalian Heart Regeneration.
The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we assemble a transcriptomic framework of multiple cardiac cell populations during postnatal development and following injury, which enables comparative analyses of the regenerative (neonatal) versus nonregenerative (adult) state for the first time. Cardiomyocytes, fibroblasts, leukocytes, and endothelial cells from infarcted and noninfarcted neonatal (P1) and adult (P56) mouse hearts were isolated by enzymatic dissociation and fluorescence-activated cell sorting at day 3 following surgery. RNA sequencing was performed on these cell populations to generate the transcriptome of the major cardiac cell populations during cardiac development, repair, and regeneration. To complement our transcriptomic data, we also surveyed the epigenetic landscape of cardiomyocytes during postnatal maturation by performing deep sequencing of accessible chromatin regions by using the Assay for Transposase-Accessible Chromatin from purified mouse cardiomyocyte nuclei (P1, P14, and P56). Profiling of cardiomyocyte and nonmyocyte transcriptional programs uncovered several injury-responsive genes across regenerative and nonregenerative time points. However, the majority of transcriptional changes in all cardiac cell types resulted from developmental maturation from neonatal stages to adulthood rather than activation of a distinct regeneration-specific gene program. Furthermore, adult leukocytes and fibroblasts were characterized by the expression of a proliferative gene expression network following infarction, which mirrored the neonatal state. In contrast, cardiomyocytes failed to reactivate the neonatal proliferative network following infarction, which was associated with loss of chromatin accessibility around cell cycle genes during postnatal maturation. This work provides a comprehensive framework and transcriptional resource of multiple cardiac cell populations during cardiac development, repair, and regeneration. Our findings define a regulatory program underpinning the neonatal regenerative state and identify alterations in the chromatin landscape that could limit reinduction of the regenerative program in adult cardiomyocytes.


JDRF randomized clinical trial to assess the efficacy of real-time continuous glucose monitoring in the management of type 1 diabetes: research design and methods.
While real-time (RT) continuous glucose monitoring (CGM) systems may revolutionize treatment of type 1 diabetes (T1D), there is insufficient evidence currently available to support widespread utilization of these devices. The Juvenile Diabetes Research Foundation (JDRF) CGM Study Group developed a randomized clinical trial to determine if RT-CGM can improve glycemic control and quality of life in children and adults with T1D. This paper presents the research design and methods that are being employed in this study. The JDRF CGM Study Group trial is a randomized, parallel group, efficacy and safety study. Subjects with T1DM who meet eligibility criteria are randomized to either standard self-monitoring of blood glucose (SMBG) alone or use of any of the three current RT-CGM systems as a supplement to SMBG. After the 6-month randomized period, the Control Group is offered use of RT-CGM, and both groups are studied for an additional 6 months. Subjects are divided into two cohorts: the Main Study Cohort includes subjects with baseline glycosylated hemoglobin (HbA1c) 7.0-10.0% inclusive, and the Exploratory Pilot Study Cohort includes subjects with HbA1c<7.0%. Difference in HbA1c is the primary outcome in the Main Study. Other outcomes include the percentage of sensor glucose values within the 70-180 mg/dL range, scores on questionnaires that assess the impact of RT-CGM on living with T1D, and the cost-effectiveness of RT-CGM. Recruitment for the study was completed on December 15, 2007. Results of this clinical trial should help establish whether or not current RT-CGM devices are beneficial to patients with T1D.


Tailoring Antimicrobial Susceptibility Testing to Individual Species of Coagulase-Negative Staphylococci: Next Up, Staphylococcus epidermidis.
Accurate detection of methicillin resistance among staphylococci is vital for patient care. Methicillin resistance is most commonly mediated by acquisition of the mecA gene, which encodes an altered penicillin binding protein, PBP2a. Application of phenotypic methods to detect mecA-mediated beta-lactam resistance in staphylococci is becoming more complex as species-specific differences are identified among coagulase-negative staphylococci (CoNS). Previously, interpretative criteria and antimicrobial susceptibility testing (AST) methods specific to the CoNS group were used to evaluate Staphylococcus epidermidis A manuscript by S. N. Naccache, K. Callan, C.-A. D. Burnham, M. A. Wallace, et al. (J Clin Microbiol 57:e00961-19, 2019, https://doi.org/10.1128/JCM.00961-19) details experiments revealing that S. epidermidis, the most common clinically isolated CoNS, requires tailored use of previously described methods and interpretive criteria to reliably identify the presence of mecA-mediated methicillin resistance.


Handgrip exercise in normal young women: a noninvasive cardiovascular assessment.
Blood pressure, heart rate, and echocardiographic parameters of left ventricular size and shortening were measured both under baseline conditions and during handgrip exercise (50% maximum handgrip effort held to fatigue) in 20 normal women (20 through 29 years of age). As a group, there was a significant increase in heart rate (72 +/- 10 vs 83 +/- 12; P less than .001), systolic blood pressure (111 +/- 8 vs 133 +/- 14 mm Hg; P less than .001), diastolic blood pressure (67 +/- 8 vs 89 +/- 12 mm Hg; P less than .001), and calculated cardiac output (4.3 +/- 1.5 vs 5.2 +/- 1.7 liters/minute; P less than .005). There was no significant change in left ventricular internal dimension in diastole or systole, shortening fraction, or calculated stroke volume. The average group response of an increase in cardiac output secondary to an increase in heart rate is similar to that of male subjects in their second decade. Individual variability in responses was of specific interest since only three of the 20 women demonstrated a totally characteristic response to handgrip exercise. Handgrip exercise in young women may not provide a uniformly characteristic response from which to predict hemodynamic changes in a given individual and may lead to clinical misinterpretation if appropriate caution is not used.


Sedentary behavior and physical inactivity from a comprehensive perspective.
To characterize the prevalence of physical activity in the population aged ≥16 years integrating sedentarism and physical inactivity. A cross-sectional study using data from the Galician Risk Behavior Data System (n=12,928) was conducted. The population was classified into four categories: physically active (active and non-sedentary), active but sedentary (active and sedentary), lightly active (inactive and non-sedentary), and extremely sedentary (inactive and sedentary). Prevalences were calculated for each category and a multinomial logistic regression model was fitted. 58.0% of the population was physically active and the remaining 42.0% presented some degree of sedentarism and/or physical inactivity. Men were more likely to be extremely sedentary. The risk of sedentarism decreased with age, and workers and/or students were prone to a higher risk of extreme sedentarism in comparison to those who reported other status. Extremely sendentary behaviors were also more common in people with higher educational levels, individuals living alone, residents of urban environments, and smokers. Joint evaluation of sedentarism and physical inactivity provides a more comprehensive and realistic picture of population behaviors related with physical activity. Since sedentarism is the most prevalent behavior, this study recommends that interventions be conducted at work and at academic environments.


Neutrophil-related cytokines and neutrophil products in bronchoalveolar lavage fluid of a patient with ANCA negative Wegener's granulomatosis.
We report a case of Wegener's granulomatosis (WG), with neutrophil accumulation in bronchoalveolar lavage fluid (BALF). Peripheral blood neutrophilia was present but the anti-neutrophil cytoplasmic antibody (ANCA) was negative. The serum and BALF levels of neutrophil-related cytokines, including interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, were increased, particularly in BALF. Plasma and BALF levels of neutrophil elastase and defensins, which are released by neutrophils and are potentially toxic to cells, were also elevated. Our findings suggest that neutrophils and neutrophil-related cytokines may play an important role in the pathogenesis of anti-neutrophil cytoplasmic antibody negative as well as anti-neutrophil cytoplasmic antibody positive Wegener's granulomatosis.


Vitamin D Insufficiency is Not Associated With Pediatric and Adolescent Immune Thrombocytopenia: A Study in Conjunction With its Receptor Genetic Polymorphisms.
Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous immunologic disorder. Vitamin D has immune-modulatory effects. The pleiotropic effects of vitamin D are exerted via vitamin D receptor (VDR) and its genetic alterations could influence its functions. In our study, we measured the serum 25-hydroxyvitamin D levels in 98 Pediatric and Adolescent ITP patients, in addition to 100 apparently healthy controls. Genetic polymorphisms of the VDR gene FokI, BsmI, ApaI, and TaqI were tested using specific restriction enzymes for each polymorphism. Vitamin D deficiency in the studied Pediatric age was a dominant factor, but it was found not to be associated with Pediatric ITP. However, patients carrying the FokI CC genotype had statistically higher vitamin D levels compared with those carrying other genotypes (P=0.036). Patients who were carriers of the BsmI G allele had a nearly 2-fold higher risk of ITP (odds ratio: 2.203; 95% confidence interval: 1.467-3.309). Therefore, the BsmI polymorphism of VDR could be considered a molecular risk factor for ITP.


Short-term storage of human spermatozoa in electrolyte-free medium without freezing maintains sperm chromatin integrity better than cryopreservation.
Previous attempts to maintain human spermatozoa without freezing were based on short-term storage in component-rich medium and led to fast decline in motility and increased incidence of chromosome breaks. Here we report a new method in which sperm are maintained without freezing in an electrolyte-free medium (EFM) composed of glucose and bovine serum albumin. Human sperm were stored in EFM or human tubal fluid medium (HTFM) or were cryopreserved, and their motility, viability, and DNA integrity were examined at different intervals. Cryopreservation led to significant decline in sperm motility and viability and induced DNA fragmentation. Sperm stored in EFM maintained motility and viability for up to 4 and 7 wk, respectively, much longer than sperm stored in HTFM (<2 and <4 wk, respectively). DNA integrity, assessed with comet assay, was also maintained significantly better in EFM than in HTFM. One-week storage in EFM yielded motility and viability similar to that of cryopreserved sperm, but DNA integrity was significantly higher, resembling that of fresh sperm. After several weeks of storage in EFM, sperm were able to activate oocytes, undergo chromatin remodeling, and form normal zygotic chromosomes after intracytoplasmic sperm injection. This study demonstrated that human spermatozoa can be stored in EFM without freezing for several weeks while maintaining motility, viability, and chromatin integrity and that 1-wk storage in EFM offers better protection of sperm DNA integrity than cryopreservation. Sperm storage in EFM may become a viable option for the physicians working in assisted reproduction technology clinics, which would avoid cryodamage.


Stenosis of a portacaval anastomosis affects circadian locomotor activity in the rat: a multivariable analysis.
The study of hepatic encephalopathy is limited by the lack of standardized experimental models to assess behavior. We have shown that rats continuously monitored while running on a wheel show abnormalities of the circadian rhythm of locomotor activity after portacaval anastomosis (PCA), such that entrainment of running activity to the light-dark cycle is severely impaired. To identify factors that affect postoperative circadian behavior, we have performed a multivariable analysis of 69 sham-operated controls and 107 rats after PCA. Our results indicate that shunt stenosis, as determined by the pressure gradient from the splenic pulp to the inferior vena cava, ameliorated the postoperative deterioration of the circadian rhythm. In addition, postoperative behavior was affected by preoperative performance, diet, and gender. Postoperative body weight gain, spleen weight, and liver atrophy did not impact this model. Because shunt stenosis is known to ameliorate hepatic encephalopathy in humans, our findings support the validity of this behavioral end point as a correlate of hepatic encephalopathy. Measurement of the pressure gradient across the anastomosis and achievement of sufficient preoperative entrainment appear critical for the standardization of the model.


A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites.
Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. Here we employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologues in plants and bacteria, other HAD proteins may be MEP pathway regulators.


Peptides targeting voltage-gated calcium channels.
Many peptides are potent and highly selective blockers or modulators of calcium channel function, and as such are valuable pharmacological tools and potentially valuable leads for the development of human therapeutics. Cone shells and spiders are rich sources of such peptides, although they are also found in scorpions and insects. In this article we compare the amino acid sequences of toxins active against calcium channels and describe their three-dimensional structures and structure-function relationships. Certain structural motifs, in particular the inhibitor cystine knot, prove to be quite common amongst this class of toxins. Aspects of the pharmacology and physiology of these toxins in mammalian systems are also discussed, with an emphasis on their application in the treatment of chronic pain. We then consider the prospects for peptide-based therapeutics targeting calcium channels for this and other indications, including the development of non-peptide (peptidomimetic) compounds based on a detailed understanding of toxin structure-function relationships.


Antibiotic resistance characteristics of environmental bacteria from an oxytetracycline production wastewater treatment plant and the receiving river.
We characterized the bacterial populations in surface water receiving effluent from an oxytetracycline (OTC) production plant. Additional sampling sites included the receiving river water 5 km upstream and 20 km downstream from the discharge point. High levels of OTC were found in the wastewater (WW), and the antibiotic was still detectable in river water downstream (RWD), with undetectable levels in river water upstream (RWU). A total of 341 bacterial strains were isolated using nonselective media, with the majority being identified as Gammaproteobacteria. The MICs were determined for 10 antibiotics representing seven different classes of antibiotics, and the corresponding values were significantly higher for the WW and RWD isolates than for the RWU isolates. Almost all bacteria (97%) from the WW and RWD samples demonstrated multidrug-resistant (MDR) phenotypes, while in RWU samples, these were less frequent (28%). The WW and RWD isolates were analyzed for the presence of 23 tetracycline (tet) resistance genes. The majority of isolates (94.2% and 95.4% in WW and RWD, respectively) harbored the corresponding genes, with tet(A) being the most common (67.0%), followed by tet(W), tet(C), tet(J), tet(L), tet(D), tet(Y), and tet(K) (in the range between 21.0% and 40.6%). Class I integrons were detected in the majority of WW and RWD isolates (97.4% and 86.2%, respectively) but were not associated with the tet genes. We hypothesize that the strong selective pressure imposed by a high concentration of OTC contributes to the wide dissemination of tetracycline resistance genes and other antibiotic resistance genes, possibly through mobile genetic elements.


The Merkel cell carcinoma challenge: a review from the fine needle aspiration service.
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin that occurs primarily in elderly or immunocompromised patients. For this report, the authors reviewed the diagnostic challenges associated with MCC encountered on their fine-needle aspiration (FNA) service and also conducted an in-depth review of the literature on MCC. A computer search for patients who were diagnosed with MCC by FNA at the authors' institution from 2006 to 2010 was conducted, and 5 patients were selected for cytologic and immunochemical analyses based on their varied and diagnostically challenging clinical presentations. The 5 selected patients had clinical findings commonly associated with MCC, including advanced age (4 of the 5 patients were ages 75-85 years) and a history of previous malignancies (3 of the 5 patients had a history of previous malignancy), and 1 patient was diagnosed with a concomitant low-grade lymphoma. The patients and their disease illustrated the protean clinical presentation of MCC and the clinical and cytologic challenges associated with this neoplasm. The current findings indicate the need for cytopathologists to be aware of the deceptive presentation of this neoplasm and its cytologic and immunochemical features to correctly diagnose this insidious neoplasm.


Revealing the Structural Evolution of Electrode/Electrolyte Interphase Formation during Magnesium Plating and Stripping with operando EQCM-D.
Rechargeable magnesium batteries could provide future energy storage systems with high energy density. One remaining challenge is the development of electrolytes compatible with the negative Mg electrode, enabling uniform plating and stripping with high Coulombic efficiencies. Often improvements are hindered by a lack of fundamental understanding of processes occurring during cycling, as well as the existence and structure of a formed interphase layer at the electrode/electrolyte interface. Here, a magnesium model electrolyte based on magnesium bis(trifluoromethanesulfonyl)imide (Mg(TFSI)2 ) and MgCl2 with a borohydride as additive, dissolved in dimethoxyethane (DME), was used to investigate the initial galvanostatic plating and stripping cycles operando using electrochemical quartz crystal microbalance with dissipation monitoring (EQCM-D). We show that side reactions lead to the formation of an interphase of irreversibly deposited Mg during the initial cycles. EQCM-D based hydrodynamic spectroscopy reveals the growth of a porous layer during Mg stripping. After the first cycles, the interphase layer is in a dynamic equilibrium between the formation of the layer and its dissolution, resulting in a stable thickness upon further cycling. This study provides operando information of the interphase formation, its changes during cycling and the dynamic behavior, helping to rationally develop future electrolytes and electrode/electrolyte interfaces and interphases.


Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4.
Latent TGFβ binding protein-4 (LTBP4) is a multi-domain glycoprotein, essential for regulating the extracellular bioavailability of TGFβ and assembly of elastic fibre proteins, fibrillin-1 and tropoelastin. LTBP4 mutations are linked to autosomal recessive cutis laxa type 1C (ARCL1C), a rare congenital disease characterised by high mortality and severely disrupted connective tissues. Despite the importance of LTBP4, the structure and molecular consequences of disease mutations are unknown. Therefore, we analysed the structural and functional consequences of three ARCL1C causing point mutations which effect highly conserved cysteine residues. Our structural and biophysical data show that the LTBP4 N- and C-terminal regions are monomeric in solution and adopt extended conformations with the mutations resulting in subtle changes to their conformation. Similar to LTBP1, the N-terminal region is relatively inflexible, whereas the C-terminal region is flexible. Interaction studies show that one C-terminal mutation slightly decreases binding to fibrillin-1. We also found that the LTBP4 C-terminal region directly interacts with tropoelastin which is perturbed by both C-terminal ARCL1C mutations, whereas an N-terminal mutation increased binding to fibulin-4 but did not affect the interaction with heparan sulphate. Our results suggest that LTBP4 mutations contribute to ARCL1C by disrupting the structure and interactions of LTBP4 which are essential for elastogenesis in a range of mammalian connective tissues.


Avian influenza virus h3 hemagglutinin may enable high fitness of novel human virus reassortants.
Reassortment of influenza A virus genes enables antigenic shift resulting in the emergence of pandemic viruses with novel hemagglutinins (HA) acquired from avian strains. Here, we investigated whether historic and contemporary avian strains with different replication capacity in human cells can donate their hemagglutinin to a pandemic human virus. We performed double-infections with two avian H3 strains as HA donors and a human acceptor strain, and determined gene compositions and replication of HA reassortants in mammalian cells. To enforce selection for the avian virus HA, we generated a strictly elastase-dependent HA cleavage site mutant from A/Hong Kong/1/68 (H3N2) (Hk68-Ela). This mutant was used for co-infections of human cells with A/Duck/Ukraine/1/63 (H3N8) (DkUkr63) or the more recent A/Mallard/Germany/Wv64-67/05 (H3N2) (MallGer05) in the absence of elastase but presence of trypsin. Among 21 plaques analyzed from each assay, we found 12 HA reassortants with DkUkr63 (4 genotypes) and 14 with MallGer05 (10 genotypes) that replicated in human cells comparable to the parental human virus. Although DkUkr63 replicated in mammalian cells at a reduced level compared to MallGer05 and Hk68, it transmitted its HA to the human virus, indicating that lower replication efficiency of an avian virus in a mammalian host may not constrain the emergence of viable HA reassortants. The finding that HA and HA/NA reassortants replicated efficiently like the human virus suggests that further HA adaptation remains a relevant barrier for emergence of novel HA reassortants.


[Development of an algorithm to predict the incidence of major depression among primary care consultants].
The reduction of major depression incidence is a public health challenge. To develop an algorithm to estimate the risk of occurrence of major depression in patients attending primary health centers (PHC). Prospective cohort study of a random sample of 2832 patients attending PHC centers in Concepción, Chile, with evaluations at baseline, six and twelve months. Thirty nine known risk factors for depression were measured to build a model, using a logistic regression. The algorithm was developed in 2,133 patients not depressed at baseline and compared with risk algorithms developed in a sample of 5,216 European primary care attenders. The main outcome was the incidence of major depression in the follow-up period. The cumulative incidence of depression during the 12 months follow up in Chile was 12%. Eight variables were identified. Four corresponded to the patient (gender, age, depression background and educational level) and four to patients' current situation (physical and mental health, satisfaction with their situation at home and satisfaction with the relationship with their partner). The C-Index, used to assess the discriminating power of the final model, was 0.746 (95% confidence intervals (CI = 0,707-0,785), slightly lower than the equation obtained in European (0.790 95% CI = 0.767-0.813) and Spanish attenders (0.82; 95% CI = 0.79-0.84). Four of the factors identified in the risk algorithm are not modifiable. The other two factors are directly associated with the primary support network (family and partner). This risk algorithm for the incidence of major depression provides a tool that can guide efforts towards design, implementation and evaluation of effectiveness of interventions to prevent major depression.


Perceived organisational support, organisational commitment and self-competence among nurses: a study in two Italian hospitals.
This study examined the contributions of perceived organisational support (POS) and organisational commitment (i.e. affective, continuance and normative) to self-competence among nurses. In high-POS environments, workers benefit from socio-emotional resources to improve their skills, while positive forms of commitment (e.g. affective commitment) create a fertile context for developing one's competencies. A cross-sectional study was conducted among the nursing staff of two Italian urban hospitals (hospital A, n = 160; hospital B, n = 192). A structured questionnaire was administered individually to the nurses. Data analysis was conducted through multi-group analysis and supplemented by a bootstrapping approach. The results showed that POS was positively related to self-competence through affective commitment. In contrast, continuance and normative commitment did not mediate this relationship. This study shows that supporting employees through caring about their well-being as well as fostering positive forms of organisational commitment increases nurses' self-competence. Nurse managers may increase support perceptions and commitment among their staff by rewarding their contributions and caring about their well-being, as well as concentrating on training strategies that improve work-related skills.


Analysis of Factors Related to Lymph Node Metastasis in Early-Stage Type 1 Endometrial Cancer: Verifying the Clinical Value of Positive Threshold of the Immunohistochemical Parameter Ki67.
Lymph node metastasis (LNM) is an important reference indicator for the prognosis of endometrial cancer (EC). Even in patients with early low-risk EC, many people still have LNM. The purpose of this study was to investigate the related factors influencing LNM in early-stage EC and determine the optimal positive threshold of immunohistochemical parameter Ki67 for predicting LNM, providing auxiliary reference indicators for clinical diagnosis and treatment. The clinicopathological data of 651 patients with "apparent" early-stage EC who underwent standard surgical treatment were included. Univariate and multivariate logistics regression were used to analyze the correlation between each clinicopathological factor and LNM. Receiver operating characteristic curve (ROC curve) and Youden index were used to determine the optimal positive threshold of Ki67 for predicting LNM. Finally, correlation between Ki67 and various clinicopathological factors was analyzed, and the predictive value of each prognostic factor was compared. Multivariate analysis found that histologic grade (P=0.023), lymphatic vessel space invasion (LVSI) (P < 0.001), serological index Ca125 (P=0.002), immunohistochemical parameter Ki67 (P < 0.001), ER (P < 0.001) and P53 (P=0.001) were independent prognostic factors of LNM. ROC curve and Youden index showed that the optimal positive thresholds of Ki67 to predict LNM were 40%. Based on this, ROC curve showed that the area under the curve (AUC) of Ki67 (AUC=0.714) was larger than other single predictors, and Ki67 combined with other predictors can significantly increase the AUC value (AUC= 0.847 and 0.868, respectively). Ki67 was an important predictor for predicting the LNM in early-stage EC and taking a positive percentage of about 40% can be used as the positive threshold of the immunohistochemical parameter Ki67. On this basis, Ki67 combined with other predictive indicators can significantly improve prediction performance and can be used for segmentally predicting LNM of early-stage EC.


Ontogeny of food deprivation effects on ornithine decarboxylase: ornithine decarboxylase induction by alpha and beta agonists.
Short-term food deprivation (FD) of preweanling rat pups causes a marked and specific suppression of liver ornithine decarboxylase (ODC) induction by alpha and beta adrenergic agonists that is mediated by postreceptor mechanisms. In the present study, we demonstrate that FD also affects the ability of adrenergic agonists to induce hepatic ODC in older animals and that these changes differ from those occurring in neonates in the duration of FD associated with changes, the subcellular mechanisms involved and the organ specificity of the effect. FD (48 hr) of 30-day-old rats caused a specific suppression of liver ODC induction by the alpha agonist phenylephrine whereas the effect of the beta agonist isoproterenol was not changed. ODC induction by vasopressin or angiotensin was unaffected, whereas the effect of aminophylline was potentiated. FD of 30-day-old rats caused a marked suppression of both alpha and beta agonist action in the heart. FD of mature (60-day-old) rats was associated with an enhanced hepatic ODC response to phenylephrine and isoproterenol. Whereas the number of receptors in heart assessed by the binding of [3H]prazosin and [125I]pindolol to alpha and beta receptors, respectively, decreased in parallel with changes in responsivity, liver ODC responses did not correlate well with receptor changes. These findings support previous findings of altered sympathetic responsivity in heart, liver and fat during FD and indicate that the sympathetic nervous system responds to FD with a complex series of changes in both pre- and postsynaptic mechanisms.


A systematic review of posterior reversible encephalopathy syndrome in pregnant women with severe preeclampsia and eclampsia.
The association of posterior reversible encephalopathy syndrome (PRES) and severe preeclampsia/eclampsia has been established but the frequency is uncertain. To determine the frequency of PRES in severe preeclampsia or eclampsia. We searched published articles in PubMed, Cochrane library, Embase, and CINAHL from 1990 to 2020. We included articles that reported on six or more cases of PRES with eclampsia or severe preeclampsia who underwent neuroimaging during pregnancy or up to 6 weeks postpartum. We identified 29 studies presenting data on 1519 women with eclampsia or severe preeclampsia. Among 342 women with eclampsia who had neuroimaging, 176 (51.4%) were diagnosed with PRES. Of 121 women with severe preeclampsia, 24 (19.8%) had PRES. The pooled maternal death rate was 5.3% (21/395). PRES is commonly reported on neuroimaging of women with eclampsia/ severe preeclampsia. The role of neuroimaging in eclampsia and especially in women with severe preeclampsia requires re-evaluation as further management is often dictated by this finding.


Breast Pain: Clinical Pattern and Aetiology in a Breast Clinic in Eastern Nigeria.
Patients with breast pain are likely to be very worried because some consider pain in the breast as an indication of malignancy. To highlight the causes of pain in the patients are presenting to our breast clinic. A prospective study of all consenting patients with breast disease presenting to the breast clinic was conducted from January 2004 to December 2008. A total of 664 patients presented to the breast clinic during the study period. Of this number, 127 presented with breast pain either as the sole symptom or in association with other symptoms. The presenting complaints were a pain, pain with lump, and pain with nipple discharge in 63 (49.6%), 59 (46.4%), and 5 (4.0%) patients, respectively. The pain was noncyclical in 96 (75.6%) patients. The site of the pain was whole breast in 87 (68.5%) patients and a lump in 40 (31.5%). The clinical diagnosis in 31 (24.4%) cases was fibrocystic disease, 28 (22.0%) cancer, 23 (18.1%) unknown, 10 (7.9%) fibroadenoma, 8 (6.3%) duct ectasia, 6 (4.7%) normal breast, and others 21 (16.5%) cases benign diseases were diagnosed. The histological diagnosis was fibrocystic changes, carcinoma, and fibroadenoma in 15 (42.9%), 10 (28.6%), and 5 (14.3%) patients, respectively. Others were benign phyllodes, abscess, duct ectasia, chronic mastitis, and lipoma, each constituting 1 (2.9%) case. Breast pain constitutes a small proportion of complaints to our breast clinic. Fibrocystic changes were the most common cause of breast pain both clinically and histologically.


REGULARIZED 3D FUNCTIONAL REGRESSION FOR BRAIN IMAGE DATA VIA HAAR WAVELETS.
The primary motivation and application in this article come from brain imaging studies on cognitive impairment in elderly subjects with brain disorders. We propose a regularized Haar wavelet-based approach for the analysis of three-dimensional brain image data in the framework of functional data analysis, which automatically takes into account the spatial information among neighboring voxels. We conduct extensive simulation studies to evaluate the prediction performance of the proposed approach and its ability to identify related regions to the outcome of interest, with the underlying assumption that only few relatively small subregions are truly predictive of the outcome of interest. We then apply the proposed approach to searching for brain subregions that are associated with cognition using PET images of patients with Alzheimer's disease, patients with mild cognitive impairment, and normal controls.


Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers.
Nateglinide is commonly used in the treatment of patients with type 2 diabetes mellitus. Our objective was to assess the association between CYP2C9 and SLCO1B1 polymorphisms and the metabolism of nateglinide in healthy Chinese male volunteers. A total of 35 healthy Chinese male volunteers with different CYP2C9 and SLCO1B1 genotypes were given a single oral dose of 120 mg nateglinide. Plasma concentrations of nateglinide and blood glucose level were measured up to 8 h. In subjects with the CYP2C9*1/*3 & 521TT, CYP2C9*1/*1 & 521TC/CC and CYP2C9*1/*3 & 521TC genotype, AUC(0-∞) of nateglinide was 56 %, 34 % and 56 % higher (P = 0.002, P = 0.041 and P = 0.013, respectively), and the CL/F of nateglinide was 35 %, 11 % and 36 % lower (P = 0.000, P = 0.003 and P = 0.002, respectively) than that in the reference group. When only considering 521 T>C polymorphism, it had no significant association with the pharmacokinetics of nateglinide. CYP2C9*3 and 521 T>C polymorphisms were the significant predictors of the AUC(0-∞) and CL/F of nateglinide (adjusted multiple R(2) = 34 % and 43 %, respectively) according to multiple linear regression analyses, but they have no significant association with changes in the blood glucose-lowering effect of nateglinide. Both SLCO1B1 521 T>C and the CYP2C9*3 polymorphisms can significantly affect the pharmacokinetics of nateglinide, but they could only partially explain the interindividual variability of plasma concentration of nateglinide. Moreover, 521 T>C and the CYP2C9*3 polymorphisms have no effect on pharmacodynamics of nateglinide in healthy Chinese male subjects.


Relationship between Fear of COVID-19, Intolerance of Uncertainty, and Coping Strategies on University Students' Mental Health.
the mental health of students was particularly affected by the COVID-19 pandemic. The present study therefore examined the relationships between anxiety and depressive symptoms, eating-related problems, coping, fear of COVID-19, and intolerance of uncertainty. 2139 French students of 54 universities were recruited in the different regions of France during a French lockdown (between 21 April and 3 May 2021). Six variables were measured: fear of COVID-19, intolerance of uncertainty, coping, anxiety and depressive symptoms, and eating-related problems. To explore the directions of the relationships between our variables of interest, we calculated a directed acyclic graph. our data highlighted the central roles of intolerance of uncertainty in students' anxiety and depressive symptoms, and the direct role of prospective intolerance of uncertainty on eating-related problems. these findings indicate that intolerance of uncertainty should be targeted by interventions designed to help students with high levels of anxiety, depressive symptoms, and/or eating-related problems.


Glottic views using a Miller size 0 blade are superior to those from a Macintosh size 0 blade in neonates: a randomized trial.
Both the Miller and Macintosh blades are commonly used during laryngoscopy in infants and children, although the glottic views have not been compared in neonates. This study compared the glottic views with the Miller and Macintosh size 0 blades in neonates when the blades were placed above and below the epiglottis. Forty anaesthetized and paralyzed neonates undergoing elective surgery were enrolled and randomized to either the Miller or Macintosh size 0 blade. Two glottic views were obtained in random order in each neonate and were photographed using the same blade: lifting the epiglottis first then the tongue base or vice versa. The percentage of glottic opening (POGO) scores were evaluated with each view. The POGO scores and cardiorespiratory variables were then analysed. The POGO scores using the Miller blade to lift both the epiglottis and the tongue base were similar, whereas the scores using the Macintosh blade to lift the epiglottis were greater than those to lift the tongue base. The POGO scores using the Miller blade in both positions were significantly greater than those using the Macintosh blade in the corresponding positions (P = 0.0001). The heart rate using the Miller blade was greater than that using the Macintosh blade (P = 0.0001). In neonates, the glottic views using the Miller size 0 blade to lift both the epiglottis and the tongue base were deemed to be excellent and superior to those using the Macintosh blade in both positions.


Assessment of newly synthesized mitochondrial DNA using BrdU labeling in primary neurons from Alzheimer's disease mice: Implications for impaired mitochondrial biogenesis and synaptic damage.
The purpose of our study was to assess mitochondrial biogenesis and distribution in murine primary neurons. Using 5-bromo-2-deoxyuridine (BrdU) incorporation and primary neurons, we studied the mitochondrial biogenesis and mitochondrial distribution in hippocampal neurons from amyloid beta precursor protein (AβPP) transgenic mice and wild-type (WT) neurons treated with oxidative stressors, rotenone and H(2)O(2). We found that after 20h of labeling, BrdU incorporation was specific to porin-positive mitochondria. The proportion of mitochondrial area labeled with BrdU was 40.3±6.3% at 20h. The number of mitochondria with newly synthesized DNA was higher in AβPP neuronal cell bodies than in the cell bodies of WT neurons (AβPP, 45.23±2.67 BrdU-positive/cell body; WT, 32.92±2.49 BrdU-positive/cell body; p=0.005). In neurites, the number of BrdU-positive mitochondria decreased in AβPP cultures compared to WT neurons (AβPP, 0.105±0.008 BrdU-positive/μm neurite; WT, 0.220±0.036 BrdU-positive/μm neurite; p=0.010). Further, BrdU in the cell body increased when neurons were treated with low doses of H(2)O(2) (49.6±2.7 BrdU-positive/cell body, p=0.0002 compared to untreated cells), while the neurites showed decreased BrdU staining (0.122±0.010 BrdU-positive/μm neurite, p=0.005 compared to the untreated). BrdU labeling was increased in the cell body under rotenone treatment. Additionally, under rotenone treatment, the content of BrdU labeling decreased in neurites. These findings suggest that Aβ and mitochondrial toxins enhance mitochondrial fragmentation in the cell body, and may cause impaired axonal transport of mitochondria leading to synaptic degeneration.


Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations.
RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode. We demonstrate that vepafestinib has best-in-class selectivity against RET, while exerting activity against commonly reported on-target resistance mutations (variants in RETL730, RETV804 and RETG810), and shows superior pharmacokinetic properties in the brain when compared to currently approved RET drugs. We further show that these properties translate into improved tumor control in an intracranial model of RET-driven cancer. Our results underscore the clinical potential of vepafestinib in treating RET-driven cancers.


Comparison of International Guidelines for Managing Chronic Heart Failure with Reduced Ejection Fraction.
Heart failure (HF), a type of cardiovascular disease (CVD), is a major cause of death globally and significantly burdens patients and the healthcare systems. Therefore, an improved treatment strategy is a necessity to reduce the mortality and morbidity rates and reduce its associated costs. Continuous updates in guidelines for the treatment of heart failure, especially for heart failure with reduced ejection fraction (HFrEF), have become evident in the last 5 years. An extensive literature search was conducted and the most recently published guideline recommendations for managing HFrEF in China, Canada, Europe, Portugal, Russia, and the United States were extracted. The differences in the treatment recommendations and the associated burdens, including mortality and morbidity rates and associated costs were analyzed. The HFrEF management guidelines recommended the clinical use of medicines belonging to 4 classes: an angiotensin II-receptor blocker plus neprilysin inhibitor (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium/glucose cotransporter-2 inhibitors (SGLT2i). Several differences in the management guidelines from resulted in significant variability in the disease burden in each country. The annual cost was the lowest in Russia, however, it showed the highest prevalence and incidence rates. In China, disease prevalence and incidence rates were the lowest and the annual cost was also comparatively low. The annual cost was highest in Canada, but it was associated with low prevalence. The annual cost was low in Portugal, but the prevalence was high. There were no significant differences in the prevalence and incidence rates as well as the annual costs between the United States and Europe. The global 5-year mortality rate of heart failure (HF) ranged between 50% and 70%. The research articles from the United States were cited the most (35.8%) in the guidelines. The results indicate differences between HFrEF management guidelines from different countries and their association with increased global disease burden. This study suggests that a unified global collaborative effort between countries is imperative to improve the guidelines for managing HFrEF to lower the associated burden for both the patients and the healthcare systems.


Life course learning experiences and infant feeding practices in rural Rwanda.
Most studies about infant and young child feeding (IYCF) practices are often perceived as an individual choice depending on mothers' or caregivers' knowledge or attitudes and are focused on mothers' failure rather than successes in adequately feeding their children. However, the role of life course experiences in IYCF is less investigated. Applying a Salutogenic Model of Health, this study on 14 mothers looks at women's life course learning experiences shaping appropriate IYCF practices during the first year of child's life in a rural district of Rwanda. Transcripts from in-depth interviews were analysed using thematic analysis. Results indicate that positive social interaction with parents or grandmothers during childhood such as sharing meals, parental role models for dietary choices and cooking skills gained by participating in household food preparation played a role in shaping appropriate IYCF practices. Negative experiences during childhood also had a positive influence on IYCF practices for some participants by converting life course constraints into learning opportunities. Motherhood increased mothers' sense of responsibility over their children's health and nutrition. Moreover, mothers' participation in community cooking classes and role modelling approach were strong avenues that enabled their learning through positive interactions and encouragement. Nutrition promotion interventions should consider tailoring nutrition advice to the complexity of mothers' life course experiences by creating opportunities for positive learning experiences of appropriate IYCF practices.


Development and validation of spectrophotometric method for simultaneous estimation of paracetamol and lornoxicam in different dissolution media.
Paracetamol and lornoxicam in combined tablet dosage form are available in the market. This combination is used to treat inflammatory diseases of the joints, osteoarthritis and sciatica. Spectrophotometric and high performance liquid chromatography (HPLC) methods have been reported for their simultaneous estimation in tablet dosage form in specific solvent. This paper presents simple, accurate and reproducible spectrophotometric method for simultaneous determination of paracetamol and lornoxicam in tablet dosage form in different dissolution media. The reported method is helpful in determination of paracetamol and lornoxicam during dissolution study. Simple, sensitive, accurate and economical spectrophotometric method based on an absorption correction equation was developed for the estimation of paracetamol and lornoxicam simultaneously in tablet dosage form in different dissolution media at different pH. Paracetamol showed absorption maxima at 243 nm in 0.1N HCland phosphate buffer pH 6.8, while lornoxicam showed absorption maxima at 374 nm in 0.1N HCland phosphate buffer pH 6.8. The linearity was obtained in the concentration range of 4-12 μg/ml for paracetamol and 4-16 μg/ ml for lornoxicam. The concentrations of the drugs were determined by an absorption correction equation method. The results of analysis have been validated statistically by recovery studies.


Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies.
Precapillary pulmonary hypertension (PH) is an important cause of death in patients with systemic sclerosis (SSc). It can occur in isolation (pulmonary arterial hypertension [PAH]) or in association with interstitial lung disease (ILD). Importantly, the outcomes and efficacy of PAH therapies in patients with SSc-related PH complicating ILD (PH-ILD) remain unknown. This study was undertaken to evaluate our experience with PH-ILD with regard to the efficacy and safety of PAH therapies in this patient cohort. We conducted a retrospective analysis of consecutive SSc patients from 2 large referral centers who had PH-ILD confirmed by right-sided heart catheterization and who received targeted PAH therapies. World Health Organization (WHO) functional class, 6-minute walk distance, and hemodynamic parameters were assessed at baseline and after a mean ± SD of 7.7 ± 6.2 months of treatment for PAH. Kaplan-Meier and Cox proportional hazards models were used to analyze survival and to identify prognostic factors. Seventy patients were included in the study. No significant changes were observed in WHO functional class, 6-minute walk distance, or hemodynamic parameters after therapy. The 1-, 2-, and 3-year survival estimates were 71%, 39%, and 21%, respectively. In the multivariate model, worsening oxygenation during followup and reduced renal function were the only significant risk factors for death. This study represents the largest series to date in which the impact of PAH therapies in SSc-related PH-ILD was examined. In this cohort, PAH therapies were associated with no clear benefits. Deterioration in oxygenation was an important determinant of long-term survival. Prospective clinical trials focusing on this group of patients are warranted.


Interactions between temperature and sugars in the regulation of leaf senescence in the perennial herb Arabis alpina L.
Annual plants usually flower and set seed once before senescence results in the death of the whole plant (monocarpic senescence). Leaf senescence also occurs in polycarpic perennials; even in "evergreen" species individual leaves senesce. In the annual model Arabidopsis thaliana sugars accumulate in the senescent leaves and senescence is accelerated by high sugar availability. Similar to A. thaliana, sugar contents increased with leaf age in the perennial Arabis alpina grown under warm conditions (22 °C day/18 night). At 5 °C, sugar contents in non-senescent leaves were higher than at a warm temperature, but dependent on the accession, either sugars did not accumulate or their contents decreased in old leaves. In A. alpina plants grown in their natural habitat in the Alps, sugar contents declined with leaf age. Growth at a cold temperature slightly delayed senescence in A. alpina. In both warm and cold conditions, an external glucose supply accelerated senescence, but natural variation was found in this response. In conclusion, sugar accumulation under warm conditions could accelerate leaf senescence in A. alpina plants, but genotype-specific responses and interactions with growth temperature are likely to influence senescence under natural conditions.


Applying theory-driven approaches to understanding and modifying clinicians' behavior: what do we know?
Despite major recent research advances, large gaps exist between accepted mental health knowledge and clinicians' real-world practices. Although hundreds of studies have successfully utilized basic behavioral science theories to understand, predict, and change patients' health behaviors, the extent to which these theories-most notably the theory of reasoned action (TRA) and its extension, the theory of planned behavior (TPB)-have been applied to understand and change clinician behavior is unclear. This article reviews the application of theory-driven approaches to understanding and changing clinician behaviors. MEDLINE and PsycINFO databases were searched, along with bibliographies, textbooks on health behavior or public health, and references from experts, to find article titles that describe theory-driven approaches (TRA or TPB) to understanding and modifying health professionals' behavior. A total of 19 articles that detailed 20 studies described the use of TRA or TPB and clinicians' behavior. Eight articles describe the use of TRA or TPB with physicians, four relate to nurses, three relate to pharmacists, and two relate to health workers. Only two articles applied TRA or TPB to mental health clinicians. The body of work shows that different constructs of TRA or TPB predict intentions and behavior among different groups of clinicians and for different behaviors and guidelines. The number of studies on this topic is extremely limited, but they offer a rationale and a direction for future research as well as a theoretical basis for increasing the specificity and efficiency of clinician-targeted interventions.


Proto-industrialization, sharecropping, and outmigration in nineteenth-century rural Westphalia.
This article examines proto-industrialization and the social relations of production in a rural parish in eastern Westphalia that experienced large-scale outmigration to the American Midwest in the mid-nineteenth century. Relying on local and individual-level Prussian tax and emigration records, the study identifies and analyses the socio-economic background of the migrant cohort in terms of proto-industrial activity and peasant economy. Preceded by the downfall of domestic textile industries due to British industrial competition, outmigration was highly selective, drawing individuals from specific socio-economic niches. Landless sharecroppers - linked by debt and labour obligations to better-off peasants and landlords - were underrepresented in the migration, while smallholding peasants and day-labourers - 'free' to commodify their labour power through the sale of home-produced textile products or seasonal migratory labour - were overrepresented. The findings of the study have implications for an understanding of the localized nature of the relations of production in proto-industrial regions, the historical nature of German emigrations, and the dynamics of the German transition to industrial capitalism in the nineteenth century.


Cardiac neoplasm, tachyarrhythmia, and anasarca in an infant.
An infant had supraventricular tachycardia and massive anasarca at birth. The supraventricular tachycardia and congestive heart failure were minimally responsive to medical therapy. At 1 month of age, a diagnosis of atrial and ventricular septal defect was made by cardiac catheterization. At 5 months of age, at an operation for pulmonary banding, a peculiar neoplasm of the right atrium was noted. On clamping and resection of the neoplasm, the supraventricular tachyarrhythmia reverted to normal sinus mechanism. The neoplasm, by light and electron microscopy, was thought to be a conduction system hamartoma and was thought to have caused the arrhythmia. A review of the literature showed that no such lesions had been reported previously.


Lipotoxicity and impaired high density lipoprotein-mediated reverse cholesterol transport in chronic kidney disease.
Chronic kidney disease (CKD) is associated with a high risk of death from cardiovascular disease. Inflammation, oxidative stress, and dyslipidemia, which are common consequences of CKD, contribute to the pathogenesis of atherosclerosis and cardiovascular disease in this population. Dyslipidemia of CKD is characterized by diminished plasma high density lipoprotein (HDL) concentration, impaired HDL anti-oxidant and anti-inflammatory activities, and elevated plasma triglyceride, very low density lipoprotein (VLDL), intermediate density lipoprotein, chylomicron remnants, and oxidized lipids and lipoproteins. The constellation of inflammation, HDL deficiency, and oxidative modification of lipoproteins can cause atherosclerosis and progression of renal disease. We have recently found lipid accumulation in the remnant kidney and the wall of aorta in rats with CKD induced by 5/6 nephrectomy. This was mediated by up-regulation of scavenger receptors involved in the influx of oxidized lipids or lipoproteins, tubular reabsorption of lipid binding proteins through megalin-cubilin complexes, upregulation of fatty acid synthesis, and downregulation of fatty acid oxidation pathways. The combination of increased lipid influx, elevated production and reduced catabolism of lipids, and impaired HDL-mediated reverse cholesterol transport can promote atherosclerosis, glomerulosclerosis, and tubulointerstitial damage. Although statins can be effective in slowing CKD progression in patients with mild-to-moderate CKD, they have consistently failed to mitigate oxidative stress, inflammation, HDL deficiency, or cardiovascular mortality in the end-stage renal disease populations. Similarly, high doses of antioxidant vitamins have failed to either ameliorate oxidative stress, inflammation, or improve overall mortality in end-stage renal disease. This article is intended to provide a brief review of the effects of CKD on HDL structure and function and pathways of lipid influx, efflux, synthesis, and catabolism in the artery wall and the diseased kidney.


On vasodilators, magnesium and second messengers.
Detailed hemodynamic studies of vasodilating compounds in anesthetized dogs were performed. Multichannel electromagnetic flowmetry at organ level showed for a number of peptide hormones and biogenic amines that each chemical entity had its own "map" of vascular responses. In contrast magnesium-ions appear to reduce vascular resistance in each vascular area, in a similar time-frame, similar dose-dependency and without changing left ventricular volume output or perfusion of any vascular bed. The restricted vascular activity of the hormones and amines is set against the homogeneity of the morphology of arteriolar walls throughout the body. The hypothesis is put forward that these compounds cause vasodilation through release of one or more metabolites from their target cells. Such a metabolite would then act as a second messenger. A number of requirements are set forth for reactions to be expected after intravenous administration of such a hypothetical metabolite. It is concluded that magnesium and may be potassium fulfill these requirements, and should therefore be considered as potential second messenger vasodilators.


A standard for hilar and intrapulmonary lymph node dissection and pathological examination in early non-small cell lung cancer.
There is considerable variation in the staging of lymph nodes (LNs) as part of tumor, node, metastasis (TNM) staging of non-small cell lung cancer (NSCLC). A new dissection and pathological examination standard for hilar and intrapulmonary LNs needs to be established for patients with early-stage T1-3N0M0 NSCLC. This study involved 3,002 patients with T1-3N0M0 NSCLC who underwent radical lobectomy or total pneumonectomy in the thoracic departments of 11 Chinese institutions between January 1999 and October 2013. The Cox model was applied for univariate and multivariate analyses in the examination of station 10, 11 LN and station 12, 13, 14 LN. A hilar and intrapulmonary standard (HI standard) was then established based on univariate and multiple-factor analyses conducted using the Cox model. Among the 3,002 patients enrolled in the study, 2,609 underwent at least one examination of station 10, 11 LN (A1), while 393 did not undergo examination of station 10, 11 LN (A0). The A0 and A1 groups had 5-year survival rates of 76% and 80%, respectively (P=0.018). Further, 1,764 patients underwent at least one examination of station 12, 13, 14 LN (B1), while 1,238 patients did not (B0). The B0 and B1 groups had 5-year survival rates of 77% and 82%, respectively (P=0.008). In total, 1,269 patients attained the HI standard (C1), and 1,733 did not (C0). The C0 and C1 groups had 5-year survival rates of 77% and 83%, respectively (P<0.001). The HI standard can improve both the prognosis and survival rates of patients with T1-3N0M0 NSCLC. This will provide important guidance for pulmonary LN dissection and pathological examination in NSCLC cases.


Folate-conjugated Fe3O4@SiO2@gold nanorods@mesoporous SiO2 hybrid nanomaterial: a theranostic agent for magnetic resonance imaging and photothermal therapy.
In this paper, we investigated the functional imaging and targeted therapeutic properties of core@multi-shell nanoparticles composed of a superparamagnetic iron oxide (SPIO) core and gold nanorods (GNRs) in the mesoporous silica shells functionalized with folic acid (Fe3O4@SiO2@GNRs@mSiO2-FA). The as-synthesized five-component hybrid nanocomposite was revealed to have insignificant cytotoxicity. Intracellular uptake of the nanoparticles was studied in the folate receptor over-expressing human epidermoid carcinoma of the nasopharynx (KB) cells. Due to their magnetic/optical properties as well as the folate targeting potential, compared with Fe3O4@SiO2@GNRs@mSiO2 nanoparticles, higher cellular uptake efficiency was observed for Fe3O4@SiO2@GNRs@mSiO2-FA nanoparticles in KB cells. Characterizations were achieved using both dark field and magnetic resonance (MR) imaging techniques. The hyperthermia induced by Fe3O4@SiO2@GNRs@mSiO2-FA nanoparticles resulted in a higher cytotoxicity in KB cells. Thus, the Fe3O4@SiO2@GNRs@mSiO2-FA hybrid nanomaterial is an effective and promising MR imaging and photothermal therapy agent for folate-receptor over-expressing cancer cells.


The effect of addition of olive oil and "Aceto balsamico di Modena" wine vinegar in conjunction with active atmosphere packaging on the microbial and sensory quality of "Lollo Verde" lettuce and rocket salad.
Fresh rocket "Eruca Sativa" and lettuce "Lollo Verde" leaves were stored with the addition of olive oil and wine vinegar "Aceto balsamico di Modena" under modified atmosphere packaging (MAP) (5% O(2)/10% CO(2)/85% N(2) for MAP A and 2% O(2)/5% CO(2)/93% N(2) for MAP B). The microbial (mesophilic, psychrotrophic bacteria and Enterobacteriacae), physical (color and firmness) and sensory parameters of samples were studied in relation to storage time (up to 10 days at 5 ± 1 °C). The effect of wine vinegar and the application of both MAP treatments reduced the growth of all bacteria populations (p < 0.05). Samples with olive oil stored under MAP A gave the best score for overall impression (3 and 2.1 for MAP A and B respectively at the 9th day of storage) while the addition of vinegar limited sensory shelf-life to 3 days (p < 0.05). Firmness was negatively affected by wine vinegar while samples with olive oil stored under MAP A maintained firmness close to normal. Color attributes were maintained better under both MAP treatments (p < 0.05).


Interventions to facilitate smoking cessation.
Tobacco use, primarily cigarette smoking, is the leading cause of preventable morbidity and mortality in the United States, and nearly one third of those who try a cigarette become addicted to nicotine. Family physicians, who see most of these patients in their offices every year, have an important opportunity to decrease smoking rates with office-based interventions. The U.S. Public Health Service recommends that primary care physicians use the five A's (Ask, Advise, Assess, Assist, and Arrange) model when treating patients with nicotine addiction. Physicians can improve screening and increase cessation rates by asking patients about tobacco use at every office visit. Behavior modification can improve long-term smoking cessation success; even brief (five minutes or less) advice on smoking cessation during an office visit can increase cessation rates. The effectiveness of nonpharmacologic treatments generally is lower; therefore, pharmacotherapy is recommended for smokers who are willing to attempt cessation, unless medical contraindications exist. The pharmacologic agents approved by the U.S. Food and Drug Administration for treatment of tobacco dependence include bupropion (a non-nicotine therapy) and nicotine replacement therapies in the form of a gum, patch, nasal spray, inhaler, and lozenge. These agents have similar long-term success rates.


[A computer-assisted noninvasive monitoring system with graphic display of online determination of cardiovascular parameters].
During anesthesia the cardiovascular system is usually assessed on the basis of heart rate and arterial pressure, although the most important hemodynamic measurement is that of flow. A method for the non-invasive measurement of cardiac output is based on thoracic electrical bio-impedance. The NCCOM3-R7 is a non-invasive cardiac output monitor that makes use of thoracic electrical bioimpedance, which has been shown to provide results comparable with thermodilution in various hemodynamic states both in animals and humans. A new on-line hemodynamic monitoring system has been developed using the non-invasive NCCOM3-R7 (BoMed) cardiac output monitor, a portable microcomputer (NEC Multispeed) in connection with a software package CDDP-1 (BoMed), a Dinamap automatic arterial pressure monitor (Critikon) and an additional 14" display. Every 16 heart beats the cardiac output monitor transfers 11 cardiodynamic parameters in ASCII-format to the microcomputer, where the data are stored. Using the CDDP-1 program the current cardiodynamic status of the patient is displayed numerically and graphically on the monitor screen. Mean arterial pressure is determined by Dinamap and the data must be entered manually in the menu. The program then calculates systemic vascular resistance and left ventricular work index, the CVP being set to 3 torr and PAOP to 6 torr. In the graphic display the current hemodynamic status is shown and the underlying situation is analyzed in terms of systemic vascular resistance and volume-dependent contractility. The reliability of this on-line monitoring system is demonstrated in a high-risk patient.(ABSTRACT TRUNCATED AT 250 WORDS)


Collagen I/III and matrix metalloproteinases (MMP) 1 and 13 in the fascia of patients with incisional hernias.
The late appearance ofincisional hernias several years after laparotomy and the high recurrence rates after operation strongly imply the presence of a disorder of the connective tissue, although a specific defect in patients with incisional hernias has not yet been identified. In the present study we used both immunohistochemistry and Western blot analysis to evaluate the ratio of collagen I and III and the expression of the metalloproteinases (MMP) 1 and 13 in the fascia of patients with incisional or recurrent incisional hernias. Samples of healthy skin or stable skin scar in patients without hernias served as controls. Altogether, our data indicated a significantly decreased ratio of collagen I/III in the fascia of patients with incisional hernias and recurrent incisional hernias. Furthermore, in these patients the expression of MMP-1 was decreased compared to the controls, whereas MMP-13 could not be detected in any fascia sample, with or without hernias present. For the first time, our results give evidence of the existence of a possible collagen disorder in these patients. The decreased ratio ofcollagen I/III is explainable due to a relative increase of collagen type III, which is known to be characterized by thin fibril diameters and lowered mechanical strength. The altered collagen ratio might be the result of the decreased activity of MMP-1, whereas the absent MMP-13 expression did not seem to modify the scar formation. Thus, our data indicate the presence of collagen metabolic disorders in patients with incisional hernias and recurrent incisional hernias. Furthermore, these results might explain the poor results of a mesh-free hernia repair, which again builds up scar tissue of inadequate collagen composition and strength.


Copper-zinc superoxide dismutase of Haemophilus influenzae and H. parainfluenzae.
Copper-zinc superoxide dismutase ([Cu,Zn]-SOD) is widely found in eukaryotes but has only rarely been identified in bacteria. Here we describe sodC, encoding [Cu,Zn]-SOD in Haemophilus influenzae and H. parainfluenzae, frequent colonists and pathogens of the human respiratory tract. In capsulate H. influenzae, sodC was found in only one division of the bacterial population, and although the protein it encoded was clearly [Cu,Zn]-SOD from its deduced sequence, it lacked enzymatic activity. In H. parainfluenzae, in contrast, active enzyme was synthesized which appeared to be secreted beyond the cytoplasm when the gene was expressed in Escherichia coli minicells. The origin of gene transcription differed between the Haemophilus species, but protein synthesis from cloned genes in vitro was comparable. A C-T transition was found in the H. influenzae sequence compared with the H. parainfluenzae sequence, leading to a histidine, known to be crucial in eukaryotic [Cu,Zn]-SOD for copper ion coordination and so for enzymatic activity, to be changed to tyrosine. This is speculated to be the cause of inactivity of the H. influenzae enzyme. Secreted SODs have only been described in a few bacterial species, and this is the first identification of [Cu,Zn]-SOD in a common human upper respiratory tract colonist. The role of secreted bacterial SODs is unknown, and we speculate that in Haemophilus species the enzyme may confer survival advantage by accelerating dismutation of superoxide of environmental origin to hydrogen peroxide, disruptive to the normal mucociliary clearance process in the host.


Lowering intercellular melatonin levels by transgenic analysis of indoleamine 2,3-dioxygenase from rice in tomato plants.
Melatonin exists in numerous living organisms including vertebrates, insects, fungi, bacteria, and plants. Extensive studies have been conducted on the physiological roles of melatonin in various plant species. In plants, melatonin seems to act in antioxidant protection, as a growth promoter, and in photoperiodism. However, the mechanisms by which melatonin carries out these roles remain unclear. We manipulated the endogenous melatonin content in tomato plants by modifying the metabolic enzyme indoleamine 2,3-dioxygenase (IDO). The OsIDO gene was isolated from rice (Oryza sativa) and characterized using 3-D homology modeling and reverse genetic approaches. The amino acid sequence of OsIDO showed high homology to the Ustilago maydis IDO. The 3-D model structure of OsIDO is composed of a small and a large domain. Transgenic tomato plants constitutively expressing the OsIDO gene exhibited a decrease in their melatonin content. Moreover, the number of lateral leaflets decreased in transgenic plants. Protein extracts taken from these plants showed activity degradation, demonstrating the function of OsIDO. These results suggest the involvement of IDO in plant melatonin metabolism and a possible role in plant leaf development.


[Genesis of great saphenous vein obliteration and its clinical manifestations after endovenous laser coagulation combined with crossectomy during the varicose vein treatment].
An analysis of results of the endovenous laser coagulation combined with crossectomy was made in 170 patients with varicose veins of lower extremities (C(VI), C(II)-C(V)). Clinical and ultrasonic data were investigated during a period of 3-5 days (45 lower extremities) and followed up in 1-3 years after operation (194 lower extremities). Three years later the absence of reflux was observed in 95.9% of cases. In 51.1% of cases, 1-2 zones of parietal and segmental hemodynamical insignificant bloodstream were detected. A recanalization of the great saphenous vein along the whole length was revealed in 8 cases out of 194 (4.1%) patients. The bloodstream was provided by affluxes in the area of a shin and a wellhead afflux of the stump of the great suphenous vein. The ultrasonic picture of recanalization was similar to that observed in post-thrombophlebitic occlusion.


The dynamics of the cell membrane coupling of the reaction of the Na, K-ATPase with ATP to the reaction with the cations.
From a functional point of view the dynamics of the cell membrane is perhaps most clearly expressed in the existence in the membrane of elements which can convert chemical bond energy into transport of cations against electrochemical gradients, i.e. elements which act as chemi-osmotic transducers. An example is the Na, K-ATPase which by hydrolysis of ATP transport Na+ out and K+ into the cell against their gradients. With Na+ the system exists in a Na+ -form with high Na+, low K+ and high ATP affinity while with K+ it exists in a K+ -form with high K+, low Na+ and low ATP affinity. The Na+ -form is a deprotonated while the K+-form is a protonated form, i.e. there is a Bohr-effect on the Na+ relative to K+ affinity. ATP has a deprotonating effect while phosphorylation of the system by ATP has a protonating effect, i.e. ATP turns the system into the Na+-form while phosphorylation by ATP turns the system into the K+-form. The change in protonation is observed as a change in conformation suggesting that protons take part in formation of the tertiary and the quarternary structure of the system. The cation sites can thus sense the difference between Na+ and K+ and the adaptation of the site to the cation leads to a change in protonation and by this to a change in the configuration of the ATP site. And vice versa the reaction with ATP changes via a change in protonation of the system the affinity of the cation sites. The chemical reaction is thus coupled to the reaction with the cations via a change in protonation which means changes in pK values of the system.


The effect of environmental pH on the physiology and surface structures of Salmonella serotype enteritidis phage type 4.
The incidence of food-poisoning caused by Salmonella serotype Enteritidis PT4 has increased. Implicated food products display pH levels between 4 and 9. Accordingly, the effect of growth at extremes of pH on the presence of surface structures and the carriage of a 38-MDa plasmid was determined by growing a clinical isolate of Enteritidis PT4 in a chemostat. Steady-state growth was possible over the pH range 4.35-9.45, corresponding to the pH extremes associated with key reservoirs implicated in outbreaks. Without pH control, cultures stabilised at pH 7.10. Growth at extremes of pH had significant effects on the distribution of cell surface structures; at pH 9.45, only 3% of cells were fimbriate compared with 52% at pH 7.10 and 20% at pH 4.35. The proportion of motile cells and the presence of flagella was also reduced at extremes of pH. A 38-MDa plasmid was present in cells grown in the chemostat at pH 7.10, but not in cells grown at pH 4.35 or pH 9.45. Thus, environmental pH may have a significant impact on the virulence potential of Enteritidis PT4.


Health status of newly arrived refugees in Toronto, Ont: Part 2: chronic diseases.
To determine the prevalence of selected chronic diseases among newly arrived refugee patients and to explore associations with key demographic factors. Retrospective chart review. Primary care clinic for refugee patients in Toronto, Ont. A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. Demographic information (age, sex, and region of birth) and prevalence of abnormal Papanicolaou test results, anemia, elevated blood pressure (BP), and markers of prediabetes or diabetes (elevated random glucose, fasting glucose, or hemoglobin A1c levels). More than half of our patients were female (56%) and the median age was 29 years. Patients originated from 87 different countries of birth. Top source countries were Hungary (210 patients), North Korea (119 patients), and Nigeria (93 patients). Most patients were refugee claimants (92%), as opposed to government-assisted refugees (5%). Overall, 11% of female patients who underwent Pap tests had abnormal cervical cytology findings, with the highest rates among women from Asia (26%, P = .028). The prevalence of anemia among children younger than 15 years was 11%; for children younger than 5 years the prevalence was 14%. Approximately 25% of women older than 15 years had anemia, with the highest rates among African women (37%, P < .001). Elevated BP was observed in 30% of adult patients older than 15 years, with higher prevalence among male patients (38%, P < .001) and patients from Europe (42%, P < .001). Laboratory markers of prediabetes or diabetes were identified in 8% of patients older than 15 years, with higher rates among patients from Europe (15%, P = .026). This study found a notable burden of chronic diseases among refugee patients, including anemia, elevated BP, and impaired glycemic control, as well as abnormal cervical cytology findings. These results underscore the importance of accessible, comprehensive primary care for refugees, with attention to prevention and management of chronic diseases in addition to management of infectious disease.


Innovation of Word Order Harmony Across Development.
The tendency for languages to use harmonic word order patterns-orders that place heads in a consistent position with respect to modifiers or other dependents-has been noted since the 1960s. As with many other statistical typological tendencies, there has been debate regarding whether harmony reflects properties of human cognition or forces external to it. Recent research using laboratory language learning has shown that children and adults find harmonic patterns easier to learn than nonharmonic patterns (Culbertson & Newport, 2015; Culbertson, Smolensky, & Legendre, 2012). This supports a link between learning and typological frequency: if harmonic patterns are easier to learn, while nonharmonic patterns are more likely to be targets of change, then, all things equal, harmonic patterns will be more frequent in the world's languages. However, these previous studies relied on variation in the input as a mechanism for change in the lab; learners were exposed to variable word order, allowing them to shift the frequencies of different orders so that harmonic patterns became more frequent. Here we teach adult and child learners languages that are consistently nonharmonic, with no variation. While adults perfectly maintain these consistently nonharmonic patterns, young child learners innovate novel orders, changing nonharmonic patterns into harmonic ones.


Acute spontaneous spinal epidural hematomas.
Although previous reports have characterized MR imaging features of spinal epidural hematomas (EDH), few cases have been reported during the acute or hyperacute phase within the first 48 hours. Our goal in this investigation was to correlate the MR imaging features of acute (< or =48 hours) spontaneous EDH with clinical management and outcome. Eight patients with acute spontaneous EDH (five men and three women; age range, 31-81 years) underwent MR imaging at 1.5 T (T1-weighted, n = 8; T1-weighted after the administration of 0.1 mmol/kg contrast material, n = 6; T2-weighted, n = 8; and T2-weighted, n = 4). The interval from symptom onset to hospital admission ranged from immediate to 5 days. Two neuroradiologists reviewed the MR images for signal characteristics, contrast enhancement, and cord compression. Treatment and clinical outcome were correlated with the imaging findings. The EDH were located in the cervical (n = 3), cervicothoracic (n = 2), thoracolumbar (n = 2), and lumbar (n = 1) regions. On T1-weighted images, the signal intensity of the EDH was isointense to spinal cord in five cases, hyperintense in two cases, and hypointense in one case and did not correlate with time to imaging. Isointensity on T1-weighted images persisted for 5 days in one case. On T2-weighted images, all EDHs were hyperintense with focal, heterogeneous hypointensity. Cord compression was severe in six patients, moderate in one patient, and minimal in one patient. Four cases were treated conservatively with complete resolution or improvement of symptoms within 1 to 3 weeks. MR imaging findings were useful in establishing the diagnosis of EDH but did not influence management or predict outcome in this series. Heterogeneous hyperintensity to cord with focal hypointensity on T2-weighted images should suggest the diagnosis of acute spinal EDH. Severity of neurologic impairment had the greatest impact on management and outcome. Nonoperative treatment may be successful in cases with minimal neurologic deficits, despite cord compression revealed by MR imaging.


Examining the phonological neighborhood density effect using near infrared spectroscopy.
Phonological density refers to the number of words that can be generated by replacing a phoneme in a target word with another phoneme in the same position. Although the precise nature of the phonological neighborhood density effect is not firmly established, many behavioral psycholinguistic studies have shown that visual recognition of individual words is influenced by the number and type of neighbors the words have. This study explored neurobehavioral correlates of phonological neighborhood density in skilled readers of English using near infrared spectroscopy. On the basis of a lexical decision task, our findings showed that words with many phonological neighbors (e.g., FRUIT) were recognized more slowly than words with few phonological neighbors (e.g., PROOF), and that words with many neighbors elicited significantly greater changes in blood oxygenation in the left than in the right hemisphere of the brain, specifically in the areas BA 22/39/40. In previous studies these brain areas have been implicated in fine-grained phonological processing in readers of English. The present findings provide the first demonstration that areas BA 22/39/40 are also sensitive to phonological density effects.


Clinical and radiologic investigation of the incidence, complications, and suitable removal times for fully impacted teeth in the Turkish population.
The aim of this research was to investigate the incidence of fully impacted teeth and their complications and to recommend suitable removal times for these teeth. One thousand patients who were referred to the Oral Surgery Clinic, Faculty of Dentistry, at Atatürk University were intraorally examined, and fully impacted teeth were determined from radiographs. The locations of fully impacted teeth and the complications they caused were recorded. A total of 110 patients with fully impacted teeth were divided into three age groups: 16 to 19 years, 20 to 35 years, and older than 35 years. The incidence of fully impacted teeth was found to be 11.00%. The maxillary left third molars in females and the mandibular left third molars in males were the most frequently impacted teeth. Complications, such as pain, cysts, resorption of the impacted or adjacent teeth, infection, crowding, and axial changes in the position of the adjacent teeth, were associated with 28.42% of impacted teeth. Impaction was most frequent in the 20- to 35-year-old group. Extraction of fully impacted wisdom teeth before they cause complication is the ideal approach. However, in economically developing countries, such as Turkey, extraction of these teeth after complications occur is the most suitable approach because of restrictions in governmental budgets and the patients' poor socioeconomic conditions and fear of dentistry and oral


Gastrointestinal parasites in goats from Monte Castelo, Santa Catarina, Brazil.
This study was carried out with the aim of estimating the degree of gastrointestinal helminth infection in goats on the Northern Plateau of Santa Catarina. Twelve young females and 11 adult females were used. Every 28 days, feces samples were taken to quantify the nematode eggs per gram of feces (EPG). Larval culturing was performed on a pool of positive samples from the same group. The fecal egg counts (FECs) ranged from zero to 10,400 EPG in the young group and zero to 7,600 EPG in the adult group. The mean FECs were between 583.3 and 4441.7 in the young group and between 418.2 and 2181.8 in the adult group. Eggs of the order Strongylida and genera Moniezia and Toxocara, and oocysts of Coccidia, were observed. The young animals were more affected and Haemonchus was the most prevalent genus in the samples.