Epidemiology and outcomes of hypoglycemia in patients with advanced diabetic kidney disease on dialysis: A national cohort study.
Patients with advanced diabetic kidney disease (DKD) behave differently to diabetic patients without kidney disease. We aimed to investigate the associations of hypoglycemia and outcomes after initiation of dialysis in patients with advanced DKD on dialysis. Using National Health Insurance Research Database, 20,845 advanced DKD patients beginning long-term dialysis between 2002 and 2006 were enrolled. We investigated the incidence of severe hypoglycemia episodes before initiation of dialysis. Patients were followed from date of first dialysis to death, end of dialysis, or 2008. Main outcomes measured were all-cause mortality, myocardial infarction (MI), and subsequent severe hypoglycemic episodes after dialysis. 19.18% patients had at least one hypoglycemia episode during 1-year period before initiation of dialysis. Advanced DKD patients with higher adapted Diabetes Complications Severity Index (aDCSI) scores were associated with more frequent hypoglycemia (P for trend < 0.001). Mortality and subsequent severe hypoglycemia after dialysis both increased with number of hypoglycemic episodes. Compared to those who had no hypoglycemic episodes, those who had one had a 15% higher risk of death and a 2.3-fold higher risk of subsequent severe hypoglycemia. Those with two or more episodes had a 19% higher risk of death and a 3.9-fold higher risk of subsequent severe hypoglycemia. However, previous severe hypoglycemia was not correlated with risk of MI after dialysis. The rate of severe hypoglycemia was high in advanced DKD patients. Patients with higher aDCSI scores tended to have more hypoglycemic episodes. Hypoglycemic episodes were associated with subsequent hypoglycemia and mortality after initiation of dialysis. We studied the associations and further study is needed to establish cause. In addition, more attention is needed for hypoglycemia prevention in advanced DKD patients, especially for those at risk patients.


Serum endocannabinoid content is altered in females with depressive disorders: a preliminary report.
Preclinical research has suggested that the endocannabinoid system may be involved in the etiology and/or treatment of depression; however, there are no published studies examining circulating endocannabinoid content in patients with clinical depression. This study examined the endocannabinoids (anandamide; AEA) and 2-arachidonylglycerol (2-AG) in serum from ambulatory, medication-free female patients diagnosed with minor or major depression, and in controls matched for demographic characteristics. Serum 2-AG content was significantly decreased in patients diagnosed with major depression, and this decrease was correlated significantly and negatively with duration of the depressive episode, such that 2-AG content was progressively lower the longer the depressive episode. While AEA was not associated with major depression PER SE, a strong negative correlation was found between serum AEA content and Hamilton ratings for cognitive and somatic anxiety, suggesting that AEA content may relate to the anxiety dimension of affective disorders. In subjects with minor depression, serum AEA was significantly elevated, with 2-AG content demonstrating a similar, but statistically insignificant trend. These are the first clinical data to indicate that the endocannabinoid system may be disturbed in affective disease, and suggest that future research is required to determine the relevance of these changes with respect to disease manifestation and pharmacotherapy.


[Fatal nanism: 3 different entities].
Three cases of congenital dwarfism are presented. All of them are lethal and represent the three better known nonviable nosologic entities: Achondrogenesis I, Achondrogesis II and Thanatophoric dwarfism. According to clinical features and radiologic data it is possible to approach the diagnosis accurately. We comment genetic, clinic, radiologic and histologic aspects of these processes. It is important to establish a differential diagnosis as these entities have different genetic basis, what influences genetic counsel.


Worry in children is related to perceived parental rearing and attachment.
In a sample of 159 primary school children, the relationship between perceived parental rearing behaviours and self-reported attachment style, on the one hand, and worry, on the other hand, was investigated. Children completed (a) the EMBU, a questionnaire measuring perceptions of parental rearing behaviours, (b) a single-item measure of attachment style, and (c) the Penn State Worry Questionnaire for Children (PSWQ-C), an index of severity of worrying. Results showed that parental rearing behaviours, in particular rejection and anxious rearing, were positively associated with worry. Thus, children who perceived their parents as more rejective and anxious reported higher levels of worry. Furthermore, self-reported attachment style appeared to be related to worry. More specifically, children who classified themselves as avoidantly or ambivalently attached displayed higher levels of worry than did children who classified themselves as securely attached. These findings are consistent with the notion that family environment factors such as parental rearing and attachment style contribute to the severity of anxiety symptoms in children.


Modulation of the biomarkers of inflammation and oxidative stress by ruminant trans fatty acids and dairy proteins in vascular endothelial cells (HUVEC).
This study aimed to determine whether dairy macronutrients alter markers of inflammation and oxidative stress in endothelial cells. Human endothelial cells (HUVEC) were treated with ruminant trans fatty acids (rTFA), either trans-vaccenic acid (tVA) or trans-palmitoleic acid (tPA), whey protein hydrolysate, leucine or combinations of rTFA and dairy protein compounds. Industrial TFA elaidic acid (EA) was also investigated and compared with rTFA. Inflammatory prostaglandins (PG) and F2-isoprostanes (F2-isoP) isomers, markers of oxidative stress, were assessed in cell supernatants by LC-MS/MS. Both tVA and tPA, as well as whey protein hydrolysate, decreased TNFα-induced PG excretion. Combinations of rTFA and dairy protein compounds decreased inflammation to a similar extent than rTFA alone. EA increased class VI F2-isoP isomers, whereas tVA mostly raised class III isomers. In summary, rTFA decreased inflammatory markers and increased oxidative stress markers in endothelial cells. Combinations of rTFA with whey proteins or leucine showed no additive effect.


Association between hyperthyroidism and risk of incident in Parkinson's disease.
Hyperthyroidism contributes to many other disease conditions, including neurodegenerative diseases. Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The purpose of this study was to investigate the risk of PD in patients with hyperthyroidism. A total of 8788 patients with hyperthyroidism and 8788 controls (without hyperthyroidism) matched by age, gender, index year, and Charlson Comorbidity Index (CCI) score were enrolled between 2000 and 2012. Patients were then followed until the end of 2013 using Taiwan's National Health Insurance Research Database, at which time participants who developed PD were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with a 95% CI of PD incidence rate between patients with hyperthyroidism and unaffected controls. Patients with hyperthyroidism had a significantly increased risk of PD compared with unaffected controls (1.21 vs 0.45 per 1000 person-years, HR: 2.69, 95% CI: 1.08-6.66) after adjusting for age, gender, CCI score, comorbidities, and antithyroid therapy. Hyperthyroidism and PD may share common manifestations. After excluding the first year of observation, a similar result is obtained (HR: 2.57, 95% CI: 1.61-4.01). Also, this study found that older age (HR: 3.74-8.53), more comorbidities (HR: 1.58-1.63), and specific comorbidities (brain injury (HR: 1.57) and cerebrovascular disease (HR: 3.44)) were associated with an increased risk of developing PD. Patients with hyperthyroidism have an increased risk of developing PD. Additional prospective clinical studies are warranted to examine the relationship between hyperthyroidism and PD and determine if there is an intervention that could reduce PD risk.


A Compact Fully Electronically Tunable Memristive Circuit Based on CCCDTA with Experimental Results.
This work presents a flux-controlled memristor structure employing a Current-Controlled Current Differencing Transconductance Amplifier (CCCDTA) with a grounded capacitor. The proposed emulator's invariant and variant parts can be safely adjustable, showing promising characteristics of up to 1.5 MHz operating frequency. Furthermore, there is no need for an additional circuit, switching mechanism or changing the circuit topology for the changing of operation modes. To justify the performance of the emulator with incremental and decremental mode operations, a Monte Carlo and temperature analysis are validated using TSMC 0.18 µm technology under a symmetrical supply voltage of ±0.9 V. Furthermore, the workability of the proposed circuit is tested with commercial elements such as ALD1116, AD844 and LM13700. When compared with other studies, the presented emulator circuit demonstrates promising performance in various features.


On the thermodynamics of microbial growth processes.
In this article, we provide a rigorous thermodynamic analysis of microbial growth process, clarify the role of the generalized degree of reduction concept as it is used in both stoichiometric equations and as a characterizing factor for thermophysical properties, and introduce a classification method to account for errors when using the generalized degree of reduction to estimate the energy and free energy contents of molecules. We maintain the advantages of using the generalized degree of reduction while correcting for the large errors in the principle of energy regularity, especially for small molecules and for nitrogen-source compounds. As a result, we obtain more accurate energy balances (heat loads) and second law constraints, and are able to clarify contradictory statements in the literature as to whether nonphotosynthesis fermentation process can produce oxygen or absorb rather than produce heat. Indeed, the answers to such questions become evident using the classification system introduced here.


Lactobacillus hokkaidonensis sp. nov., isolated from subarctic timothy grass (Phleum pratense L.) silage.
Four strains of Gram-positive, non-spore-forming, rod-shaped, catalase-negative and non-motile lactic acid bacteria, LOOC260(T), LOOC253, LOOC273 and LOOC279, were isolated from timothy grass (Phleum pratense L.) silage produced in Hokkaido, a subarctic region of Japan. These isolates grew at 4-37 °C, indicating the psychrotolerant nature of these strains. Phylogenetic analysis on the basis of 16S rRNA and pheS gene sequences, as well as biochemical and physiological characteristics, indicated that these four strains were members of the genus Lactobacillus. 16S rRNA gene sequence analysis of strain LOOC260(T) demonstrated that the closest neighbours were the type strains of Lactobacillus suebicus (97.7 %), Lactobacillus oligofermentans (96.7 %) and Lactobacillus vaccinostercus (96.7 %). Strain LOOC260(T) showed low levels of DNA-DNA association with Lactobacillus suebicus JCM 9504(T) (14.7 ± 3.5 %), Lactobacillus oligofermentans JCM 16175(T) (15.1 ± 4.8 %) and Lactobacillus vaccinostercus JCM 1716(T) (10.7 ± 3.0 %). The cell wall contained meso-diaminopimelic acid and the major fatty acids were C18 : 1ω9c and C19 : 1 cyclo 9,10. On the basis of phenotypic, physiological and phylogenetic evidence, these isolates represent a novel species of the genus Lactobacillus, for which the name Lactobacillus hokkaidonensis sp. nov. is proposed. The type strain is LOOC260(T) ( = JCM 18461(T) = DSM 26202(T)).


Development of Momentary Appetite Capture (MAC): A versatile tool for monitoring appetite over long periods.
Understanding how an intervention impacts appetite in real-life settings and over several days remains a challenging and under-explored research question. To this end, we developed Momentary Appetite Capture (MAC), a form of ecological momentary assessment that combines automated text messaging with an online platform. Participants report their appetite using visual-analogue scales (hunger, desire to eat, and fullness) and a virtual portion-size selection task. In two separate studies, we assessed the feasibility and test-retest reliability of MAC. Participants were prompted every 2 h over a 14-h window, and they repeated this assessment over two consecutive weekdays. For each participant, we calculated a daily time-averaged area under the curve (AUC) for each appetite measure. In Study One (N = 25) time-averaged AUC was significantly positively correlated across test days for hunger (r = 0.563, p = .003), desire to eat (r = 0.515, p = .008) and prospective portion size (r = 0.914, p < .001), but not for fullness (r = 0.342, p = .094). Participants completed 95% of MACs (380 of 400), and we used participant feedback to improve the MAC tool and study protocol for Study Two. In Study Two (N = 31), 94% of MACs were completed (468 of 496). Across days, time-averaged AUC was significantly positively correlated for hunger (r = 0.595, p = < .001), fullness (r = 0.501, p = .004), desire to eat (r = 0.585, p < .001), and prospective portion size (r = 0.757, p < .001). Together, these studies suggest that MAC could be an acceptable and reliable tool to track appetite throughout the day. In the future, MAC could be used to explore the impact of weight-loss interventions on natural fluctuations in appetite.


Basal C-peptide Level as a Surrogate Marker of Subclinical Atherosclerosis in Type 2 Diabetic Patients.
Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients. Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed. A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III, P=0.001; IDF, P<0.001; WHO, P=0.029). The multiple regression analysis between intima-media thickness (IMT) and clinical values showed that basal C-peptide significantly correlated with IMT (P=0.043), while the analysis between the 10-year coronary heart disease risk by the United Kingdom Prospective Diabetes Study risk engine and clinical values showed that basal C-peptide did not correlate with IMT (P=0.226). Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.


Sex Genotyping Mice by Polymerase Chain Reaction.
A simple method to determine the genetic sex of a mouse is to amplify DNA from a male-specific gene by polymerase chain reaction (PCR). This protocol is used to detect the Y-chromosome-specific gene Sry in tissue lysates of tail tip or ear punch samples.


Fine structure of the choroidal coat of the avian eye. Vascularization, supporting tissue and innervation.
To clarify further the functional anatomy of the avian choroid, including its innervation, 12 adult White-Leghorn chickens were studied by standard electron microscopy and immunoelectron microscopy with somatostatin antibody. The endothelial cells of the blood vessels in the choriocapillaris have fenestrations only facing the retina, while the nuclei are situated toward the sclera. In addition to tight junctions and zonulae adherentes, adjoining endothelial cells form gap junctions and dense plaques with attached filaments resembling those of smooth muscle cells. The fine structure of arteries and veins is similar to that of the vasculature described in other organs. The supporting tissue is organized in trabeculae, i.e., bridges of cellular and fibrous elements that surround and sustain blood and lymphatic vessels. This tissue consists primarily of a system of fusiform or star-shaped smooth muscle cells, connected to each other and to those in the vessels' walls through macular junctions of the adherent type, less prominent than desmosomes, and perhaps also punctiform gap junctions. Occasionally, trabecular smooth muscle cells approach the lymphatic vessels, which lack a muscular tunica, and abut their endothelium with spinous appendages. This stromal muscle tissue may act as a pump for moving the lymph. The suprachoroidea consists of large lymphatic lacunae and the multilayered membrana fusca. The elongated fuscal cells form adherent junctions, tight junctions, and perhaps also gap junctions, suggesting that the membrana fusca exerts complex functions. Nerves containing myelinated axons reach the choroid and divide into smaller branches, a few of which innervate the membrana fusca. Numerous, thin nerve branches reach both the walls of arteries and veins and the trabeculae, and synaptic terminals abut the outer muscular layers of the vessel's wall and the smooth muscle cells of the supporting tissue. Immunocytochemistry reveals the presence of numerous somatostatin-positive and somatostatin-negative axons and synaptic terminals within both trabeculae and vascular tunica media. The somatostatin-positive axons are presumed to be cholinergic axons of the choroid neurons residing in the ciliary ganglion. Taken together, these observations indicate that the avian choroid is a highly vascularized muscular sheath that may be endowed with degrees of motility and elasticity higher than those of the mammalian choroid and may therefore play an important role in compensation for experimental defocus.


Estimating frontal and parietal involvement in cognitive estimation: a study of focal neurodegenerative diseases.
We often estimate an unknown value based on available relevant information, a process known as cognitive estimation. In this study, we assess the cognitive and neuroanatomic basis for quantitative estimation by examining deficits in patients with focal neurodegenerative disease in frontal and parietal cortex. Executive function and number knowledge are key components in cognitive estimation. Prefrontal cortex has been implicated in multilevel reasoning and planning processes, and parietal cortex has been associated with number knowledge required for such estimations. We administered the Biber cognitive estimation test (BCET) to assess cognitive estimation in 22 patients with prefrontal disease due to behavioral variant frontotemporal dementia (bvFTD), to 17 patients with parietal disease due to corticobasal syndrome (CBS) or posterior cortical atrophy (PCA) and 11 patients with mild cognitive impairment (MCI). Both bvFTD and CBS/PCA patients had significantly more difficulty with cognitive estimation than controls. MCI were not impaired on BCET relative to controls. Regression analyses related BCET performance to gray matter atrophy in right lateral prefrontal and orbital frontal cortices in bvFTD, and to atrophy in right inferior parietal cortex, right insula, and fusiform cortices in CBS/PCA. These results are consistent with the hypothesis that a frontal-parietal network plays a crucial role in cognitive estimation.


Prokaryotic recombinant hemagglutinin-neuraminidase protein enhances the humoral response and efficacy of commercial Newcastle disease vaccines in chickens.
The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) plays an important role in the pathogenesis of Newcastle disease (ND). Recombinant HN (rHN) protein, produced either by direct injection of recombinant viruses containing HN gene or baculovirus expression systems, has been used to elicit immunity against NDV in chickens. In the present study, a 60.4-kDa rHN was expressed by a prokaryotic expression system and formulated into ND vaccines. Inclusion of rHN (10 microg/ml) into conventional, inactivated ND vaccines significantly (P < 0.05) increased the titer of serum hemagglutination-inhibition Ab in specific-pathogen-free or commercial chickens. Furthermore, when the rHN protein was formulated into ND+IC (infectious coryza) bivalent or ND+IC+FC (fowl cholera) multivalent vaccines, the protection rate of immunized chickens increased from approximately 80%-90% to 100% after being challenged by a velogenic strain of NDV. Our data indicated that inclusion of rHN protein produced by an economical prokaryotic expression system could enhance the immunogenicity of traditional and multivalent inactivated ND vaccines. This approach may be adapted to improve the efficacy of ND vaccines currently used in the poultry industry.


Low-Radiation Cellular Inductive Powering of Rodent Wireless Brain Interfaces: Methodology and Design Guide.
This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained.


Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells.
The influence of the antidiabetic sulphonylurea tolbutamide on K+ channels of mouse pancreatic beta-cells was investigated using different configurations of the patch clamp technique. The dominant channel in resting cells is a K+ channel with a single-channel conductance of 60 pS that is inhibited by intracellular ATP or, in intact cells, by stimulation with glucose. In isolated patches of beta-cells membrane, this channel was blocked by tolbutamide (0.1 mM) when applied to either the intracellular or extracellular side of the membrane. The dose-dependence of the tolbutamide-induced block was obtained from whole-cell experiments and revealed that 50% inhibition was attained at approximately 7 microM. In cell-attached patches low concentrations of glucose augmented the action of tolbutamide. Thus, the simultaneous presence of 5 mM glucose and 0.1 mM tolbutamide abolished channel activity and induced action potentials. These were not produced when either of these substances was added alone at these concentrations. The inhibitory action of tolbutamide or glucose on the K+ channel was counteracted by the hyperglycaemic sulphonamide diazoxide (0.4 mM). Tolbutamide (1 mM) did not affect Ca2+-dependent K+ channels. It is concluded that the hypo- and hyperglycaemic properties of tolbutamide and diazoxide reflect their ability to induce the closure or opening, respectively, of ATP-regulated K+ channels.


Improvement of Parent's awareness, knowledge, perception, and acceptability of human papillomavirus vaccination after a structured-educational intervention.
Regardless of the disease burden of human papillomavirus (HPV), the vaccine has not been included in the Indonesia National Immunization Program. Since 2017 there was a demonstration program of the HPV vaccination in Yogyakarta Province. This vaccine was given free to female primary school students in the 5th and 6th grades (11-13 years old). This study aimed to assess whether a structured-educational intervention focus on HPV increases the parental awareness, knowledge, and perceptions toward HPV and the vaccine acceptability. We conducted a pre-post structured-educational intervention study from July to August 2017 before the implementation of the HPV vaccination demonstration program, in Kulon Progo District, Yogyakarta Province, Indonesia. Parents of female primary school students grades 5th and 6th were selected using a school-based proportional random sampling. A pediatric resident provided a structured-educational intervention, which consists of the burden and risk of HPV disease, as well as the benefit and safety of the vaccine. Parents were required to complete validated self-administered questionnaires before and after the structured-educational intervention. A total of 506 parents participated. Before receiving the structured-educational intervention, parents' awareness of HPV infection and the vaccines were low. Only 49.2% of parents had heard HPV infection, and 48.8% had heard about the vaccine. After the structured-educational intervention, there were significant improvements in parent's awareness, knowledge, and perceptions of HPV infection, cervical cancer, and HPV vaccination (all p < 0.001). HPV vaccine's acceptability increased from 74.3 to 87.4% (p < 0.001). There was a significant correlation between increasing HPV vaccine acceptability with the improvement of awareness, knowledge, and perception toward HPV infection, cervical cancer and HPV vaccination (r = 0.32 to 0.53, p < 0.001). After the structured-educational intervention, better knowledge and positive perceptions of HPV vaccination were predictive of HPV vaccine's acceptability with OR 1.90 (95%CI:1.40-2.57) and OR 1.31(95%CI,1.05-1.63), respectively. A structured-educational intervention may improve parental awareness, knowledge, and perceptions toward HPV and the acceptability of the vaccine. Further study, a randomized control trial with longer follow-up are needed to evaluate the long-term and actual effectiveness of improving parents' knowledge, perceptions and HPV vaccine acceptability.


Continuous and intermittent exercise responses in individuals with chronic obstructive pulmonary disease.
While the acute physiological responses to continuous exercise have been well documented in individuals with chronic obstructive pulmonary disease (COPD), no previous study has examined the response to intermittent exercise in these patients. We examined the physiological responses of 10 individuals with moderate COPD (forced expiratory volume in 1 second 52 (15)% predicted) who performed both an intermittent (1 min exercise and rest intervals) and a continuous cycle ergometer test on separate days. Both intermittent and continuous exercise tests were performed at the same power output, calculated as 70% of the peak power attained during an incremental exercise test. Intermittent exercise was associated with significantly lower values for oxygen uptake, carbon dioxide output, expired ventilation, heart rate, plasma lactate concentration, and ratings of breathlessness than continuous exercise. Subjects were able to complete a significantly greater total amount of work during intermittent exercise (71 (32) kJ) than during continuous exercise (31 (24) kJ). The degree of dynamic lung hyperinflation (change in end expiratory lung volume) was significantly lower during intermittent exercise (0.23 (0.07) l) than in continuous exercise (0.52 (0.13) l). The greater amount of work performed and lower measured physiological responses achieved with intermittent exercise may allow for greater peripheral training adaptations in individuals with more limited lung function. The results suggest that intermittent exercise may be superior to continuous exercise as a mode of training for patients with COPD.


Inhibition of the acute toxicity and adrenocorticolytic effect of 7,12-dimethylbenz(a)anthracene by isopropylvaleramide and allylisopropylacetamide in the rat.
Isopropylvaleramide (IVA) and allylisopropylacetamide (AIA) inhibit hemorrhagic adrenocortical necrosis and mortality caused by 7,12-dimethylbenz(a)anthracene (DMBA) in female Sprague-Dawley rats. Unlike their effect on hepatic microsomal cytochrome P-450, the anti-DMBA action of these compounds does not depend on the presence of the reactive allyl group in the molecule. Similarly, related barbiturates, regardless of whether they contain, like AIA, an allyl group and consequently destroy cytochrome P-450 (secobarbital and aprobarbital) or have, like IVA, saturated side chains and therefore do not effect the microsomal hemoprotein (pentobarbital and phenobarbital), proved ineffective in preventing both adrenal damage and death caused by DMBA. Hence, the protective action of IVA and AIA cannot be attributed to the destruction of the microsomal enzyme system responsible for the activation of DMBA. The toxicity of another carcinogen, dimethylnitrosamine, which also requires metabolic activation by microsomal enzymes, is not influenced by either IVA or AIA. IVA, which counteracts the adrenocorticolytic action of DMBA when given prior to, simultaneously with, or even after this carcinogen, has no discernible effect on hydrocarbon metabolism in vivo or in vitro. IVA is one of the most powerful inhibitors of the acute toxicity of DMBA. It has the simplest aliphatic structure and the smallest molecule among protectors of the adrenals against hydrocarbon-induced damage; its mechanism of action awaits further elucidation.


[Diseases charted in the Nederlandsch Tijdschrift voor Geneeskunde, 1857-1880].
On the basis of the miasma theory and the contagion theory a comparison is presented of the 'cartography' in the epidemiology of the early years of the Nederlandsch Tijdschrift voor Geneeskunde and the present. The importance of publication of 'disease charts' then and now is illustrated with examples. Understanding, with the aid of charts, of the typical patterns of distribution of diseases, infectious and noninfectious, is still a cornerstone of their control.


G9A promotes tumor cell growth and invasion by silencing CASP1 in non-small-cell lung cancer cells.
Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related death worldwide. Although epigenetic deregulation is known to be important for tumor progression, the molecular mechanisms in NSCLC remain unclear. Here, we found that G9A (known as EHMT2), a histone methyltransferase responsible for mono- or di-methylation of histone 3 (H3) lysine 9 (K9), is significantly upregulated in NSCLC. Knocking down G9A or pharmacological inhibition of its activity suppressed tumor cell growth, colony formation, invasion and migration. Furthermore, G9A exerts these functions by repressing CASP1 expression. Knocking down CASP1 in G9A-deficient cell restored capacities of tumor cell invasion and migration. Mechanistically, G9A silences the CASP1 promoter activity by increasing H3K9me2 around its promoter. Finally, high expression of G9A or low expression of CASP1 is correlated with poor overall survival in lung adenocarcinoma. Overall, our study uncovers a novel mechanism of G9A promoting tumor cell growth and invasion by silencing CASP1, and implies that G9A may serve as a therapeutic target in treating NSCLC.


The Health Utility and Valuation of Cosmetic Rhinoplasty.
Importance: The importance of this study is to understand the impact of rhinoplasty as perceived by society and to conceptualize the health utility metric of cosmetic rhinoplasty in relation to other health interventions. Objective: This novel study seeks to measure and quantify the health state utility and valuation of cosmetic rhinoplasty. Design, Setting, Participants: This is a cross-sectional survey administered through public online forums to 161 casual observers in America. Main Outcomes and Measures: Participants were shown pre- and postoperative photographs of six patients who underwent cosmetic rhinoplasty and two patients who did not undergo surgery. Observers were asked to imagine that the external nose in each image was on their own face and rated (1) their health state utility and (2) how much they were willing to pay (WTP) to have the ideal nose. Results: Established metrics of standard gamble and visual analog scale were explored in detail. Using these valuation and health utility data, we calculated WTP per quality-adjusted-life-year (WTP/QALY). The WTP/QALY for cosmetic rhinoplasty is $12,264 per QALY, which is significantly below cost-effective thresholds. Participants were willing to accept 10% risk of death to undergo cosmetic rhinoplasty. Conclusions and Relevance: Calculating WTP/QALY as a metric, we assess and quantify the social importance of rhinoplasty. This is the first study to demonstrate that elective cosmetic rhinoplasty can be a high-value intervention as perceived by society. Furthermore, the high percentage of risk of death that participants are willing to accept for cosmetic rhinoplasty suggests there is a profound psychosocial impact of external nasal deformity. These findings have implications for patients, surgeons, and health policy makers.


Customised hinged knee replacements as a salvage procedure for failed total knee arthroplasty.
Failure of knee arthroplasty can lead to significant pain and functional disability. In a small number of patients with fracture, sepsis or massive bone loss they are considered for arthrodesis or above knee amputation. The purpose of this study was to investigate the results and complications of using customised hinged knee replacements in their place. Since 1993, 30 of the 280 (10.7%) revision knee replacements in the Avon Orthopaedic Centre, Bristol have used Endo customised hinged knee prostheses (21 rotating, nine fixed) for salvage of limb threatening situations in elderly patients. Surgical indications were 22 low periprosthetic fractures (with or without aseptic loosening), five massive aseptic osteolyses, and three deep infections. The mean length of post-operative hospital stay was just 14.6 days and all patients were discharged walking with aids. At follow up (mean 3.0 years, range 0.5-9.3 years) nine patients had died with their prostheses in situ and functioning. Six patients developed deep sepsis, two of which underwent above knee amputation, and two had received further surgery for septic problems. Two patients required further surgery for prosthetic disarticulation and one patient had successful on table vascular repair. Twenty-five patients had mid- or long- term follow up. Their mean American Knee scores (AKS) were 69.8 for knee and 35.6 for function (maximum 100), with mean total knee flexion 83 degrees. Mean Oxford knee scores (OKS) and WOMAC scores (both scored between 12 and 60 with low score indicating less difficulties) were 34.0 and 30.5, respectively. Customised hinge revision knee replacements gave rapid rehabilitation and hospital discharge. Complications were high but at mid- and long-term review, no prostheses had failed from an aseptic cause and most of the knees of this challenging group were providing both stability and flexion.


Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma.
Loss of expression of the heparan sulfate proteoglycan syndecan-1 leads to reduced cell adhesion, increased invasive potential, and dysregulated growth of mammary epithelial cells in vitro. We compared syndecan-1 expression in malignant and nonmalignant breast tissues using immunohisto-chemistry with monoclonal antibody B-B4. Staining for syndecan-1 is greatly diminished on malignant cells within infiltrating ductal carcinomas (n = 20) as compared with ductal epithelium of both normal breast (n = 14) and stromal-epithelial neoplasms (n = 10), which exhibit extensive basolateral epithelial staining. Surprisingly, comparison of malignant and nonmalignant breast tissue also reveals a striking difference in expression of syndecan-1 within the stromal compartment. In infiltrating ductal carcinomas, strong staining for syndecan-1 is present both within the connective tissue and on stromal cell surfaces, whereas syndecan-1 expression is absent in the stroma of both normal breast and stromal-epithelial neoplasms. Because syndecan-1 interacts with heparin-binding growth factors such as FGF-2, accumulation of syndecan-1 within the tumor stroma may contribute to the extensive angiogenesis and stromal proliferation characteristic of infiltrating breast carcinoma. Moreover, the induction of syndecan-1 within the stroma, coupled with the loss of syndecan-1 on malignant cells, suggests that changes in syndecan-1 expression are critical in promoting the metastatic phenotype of infiltrating ductal carcinoma of the breast.


Implications for industrial application of bioflocculant demand alternatives to conventional media: waste as a substitute.
The biodegradability and safety of the bioflocculants make them a potential alternative to non-biodegradable chemical flocculants for wastewater treatment. However, low yield and production cost has been reported to be the limiting factor for large scale bioflocculant production. Although the utilization of cheap nutrient sources is generally appealing for large scale bioproduct production, exploration to meet the demand for them is still low. Although much progress has been achieved at laboratory scale, Industrial production and application of bioflocculant is yet to be viable due to cost of the production medium and low yield. Thus, the prospects of bioflocculant application as an alternative to chemical flocculants is linked to evaluation and utilization of cheap alternative and renewable nutrient sources. This review evaluates the latest literature on the utilization of waste/wastewater as an alternative substitute for conventional expensive nutrient sources. It focuses on the mechanisms and metabolic pathways involved in microbial flocculant synthesis, culture conditions and nutrient requirements for bioflocculant production, pre-treatment, and also optimization of waste substrate for bioflocculant synthesis and bioflocculant production from waste and their efficiencies. Utilization of wastes as a microbial nutrient source drastically reduces the cost of bioflocculant production and increases the appeal of bioflocculant as a cost-effective alternative to chemical flocculants.


Hospitalists and intensivists in the medical ICU: a prospective observational study comparing mortality and length of stay between two staffing models.
A shortage of critical care specialists or intensivists, coupled with expanding United States critical care needs, mandates identification of alternate qualified physicians for intensive care unit (ICU) staffing. To compare mortality and length of stay (LOS) of medical ICU patients cared for by a hospitalist or an intensivist-led team. Prospective observational study. Urban academic community hospital affiliated with a major regional academic university. Consecutive medical patients admitted to a hospitalist ICU team (n = 828) with selective intensivist consultation or an intensivist-led ICU teaching team (n = 528). Endpoints were ICU and in-hospital mortality and LOS, adjusted for patient differences with logistic and linear regression models and propensity scores. The odds ratio adjusted for disease severity for in-hospital mortality was 0.8 (95% confidence interval [CI]: 0.49, 1.18; P = 0.23) and ICU mortality was 0.8 (95% CI: 0.51, 1.32; P = 0.41), referent to the hospitalist team. The adjusted LOS was similar between teams (hospital LOS difference 0.9 days, P = 0.98; ICU LOS difference 0.3 days, P = 0.32). Mechanically ventilated patients with intermediate illness severity had lower hospital LOS (10.6 vs 17.8 days, P < 0.001) and ICU LOS (7.2 vs 10.6 days, P = 0.02), and a trend towards decreased in-hospital mortality (15.6% vs 27.5%, P = 0.10) in the intensivist-led group. The adjusted mortality and LOS demonstrated no statistically significant difference between hospitalist and intensivist-led ICU models. Mechanically ventilated patients with intermediate illness severity showed improved LOS and a trend towards improved mortality when cared for by an intensivist-led ICU teaching team.


Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbit.
Primary afferent neurons innervating muscle spindles in jaw-closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike-triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw-closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw-opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw-closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons.


Catalytic upgrading of butyric acid towards fine chemicals and biofuels.
Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals.


Drinking patterns and the association between socio-demographic factors and adolescents' alcohol use in three metropolises in China.
The current study was designed to investigate the drinking patterns and association between socio-demographic factors and adolescents' alcohol use among high school students from China's three metropolises, Beijing, Shanghai, and Guangzhou. Using a self-administered questionnaire, we conducted a cross-sectional survey among 13,811 high school students from 136 schools between May and June 2013. A two-stage stratified sampling method was used for subject selection. The prevalence of lifetime drinking was 52.5%; in addition, 38.5% of the students were past-year drinkers, while 20.1% of them had consumed alcohol in the past 30 days. During the past year, 29.7% of the students reported that they drank once per month or less, and 22.0% of the students drank less than one standard drink (SD) per occasion. For the students who were not living with their mothers, as well as the students in higher socioeconomic status (SES), the adjusted odds of past and current drinking were significantly higher, compared with those who lived with both parents and low SES. Due to the high prevalence of alcohol consumption among junior and senior high school students in metropolises, attention should be paid by parents, school administrators, educational and public health agencies for making efforts collectively to reduce alcohol availability and drinking among adolescents.


Trans-10,cis-12 CLA increases liver and decreases adipose tissue lipids in mice: possible roles of specific lipid metabolism genes.
Although consumption of CLA mixtures has been associated with several health effects, less is known about the actions of specific CLA isomers. There is evidence that the t10,c12-CLA isomer is associated with alterations in body and organ weights in animals fed CLA, but the mechanisms leading to these changes are unclear. The purpose of this study was to determine the effects of two commonly occurring isomers of CLA on body composition and the transcription of genes associated with lipid metabolism. Eight-week-old female mice (n = 11 or 12/group) were fed either a control diet or diets supplemented with 0.5% c9,t11-CLA or t10,c12-CLA isomers or 0.2% of the peroxisome proliferator-activated receptor alpha (PPARalpha) agonist fenofibrate for 8 wk. Body and retroperitoneal adipose tissue weights were significantly lower (6-10 and 50%, respectively), and liver weights were significantly greater (100%) in the t10,c12-CLA and the fenofibrate groups compared with those in the control group; body and tissue weights in the c9,t11-CLA group did not differ from those in the control group. Livers from animals in the t10,c12-CLA group contained five times more lipids than in the control group, whereas the lipid content of the fenofibrate group did not differ from that in the control group. Although fenofibrate increased the mRNA for PPARalpha, t10,c12-CLA decreased it. These results suggest that PPARalpha did not mediate the effects of t10,c12-CLA on body composition. The CLA isomers and fenofibrate altered mRNA levels for several proteins involved in lipid metabolism, but the most striking difference was the reduction of mRNA for leptin and adiponectin in the t10,c12-CLA group. These initial results suggest that changes associated with energy homeostasis and insulin action may mediate the effects of t10,c12-CLA on lipid metabolism.


Bioaccessibility of lead in high carbonate soils.
Metal bioaccessibility is not currently considered in the French human health risk assessment procedure. For contaminants such as Pb this parameter could have a significant effect on the risk calculation. From the literature, it seems that Pb bioaccessibility is strongly controlled by the occurrence of cerrussite in soils: with a high cerussite content showing a positive correlation with high Pb bioaccessibility. Assuming this hypothesis, Pb contained in carbonated soils could show strong human bioaccessibility. This study aims to examine the link between high carbonate soil minerals, focussing particularly on cerrussite and the Pb bioaccessibility. Four soils were sampled in a high carbonate area in France contaminated with Pb due to mining activities. Pb bioaccessibility was measured using the in vitro RIVM protocol. In parallel, the solid phase Pb distribution was determined using chemical sequential extraction for each sample and physical analysis on the more contaminated sample. Results showed that Pb bioaccessibility was significantly different among soil samples. As shown in literature, cerussite (PbCO3) was a highly bioaccessible phase and 40% of Pb in the waste material was present in this form. However, cerussite alone did not account for all of the Pb which was also present in highly stable minerals containing sulphur. Pb associated to these minerals is also likely to be significantly bioaccessible. Indeed, sequential extraction showed that most of the Pb was associated with the sulphur-compartment. This study shows that Pb bioaccessibility in high carbonate soils can be low (down to 20% of the total soil Pb content) and is not correlated with cerussite soil contents even if the concentration of this mineral is relatively high. Consequently, risk management of Pb contamination should not focus only on high carbonate soils but also on Pb contained in other minerals which is also likely to be significantly bioaccessible.


Interleukin-1 receptor antagonist suppresses experimental autoimmune encephalomyelitis (EAE) in rats by influencing the activation and proliferation of encephalitogenic cells.
Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although the role of CD4+ T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated, the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. We have evaluated the effect of human recombinant interleukin-1 receptor antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 microg/rat/day) developed milder signs of EAE, when compared to saline-treated control animals immunized with encephalitogen, which developed severe single episode disease. The transfer of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 microg/ml) developed significantly milder disease. Diminished encephalitogenic capacity of LNC correlated with lower proliferative response to antigen and mitogen and decreased expression of IL-2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lymphocytes.


Role of oxaliplatin combined with 5-fluorouracil and folinic acid in the first- and second-line treatment of advanced colorectal cancer.
What is the role of oxaliplatin combined with 5-fluorouracil (5-fu) and folinic acid (fa) in the first- and second-line treatment of advanced (unresectable locally advanced or metastatic) colorectal cancer? Evidence was selected and reviewed by two members of the Gastrointestinal Cancer Disease Site Group (gi dsg) of Cancer Care Ontario's Program in Evidence-Based Care (pebc) and by a methodologist. The resulting practice guideline report has been reviewed and approved by the gi dsg, which comprises medical and radiation oncologists, surgeons, a pathologist, and patient representatives. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the original guideline report was obtained from the Practice Guidelines Coordinating Committee. Outcomes of interest were 1-year survival, response rates, and quality of life. The medline, cancerlit, embase, Guidelines International Network, and Cochrane Library databases were systematically searched for relevant studies. Recommendations were formed based on the evidence reviewed. Through a survey, these recommendations were appraised by Ontario clinicians; the recommendations were then revised by the gi dsg. The systematic review and modified recommendations were approved by a review body within pebc. The literature review found twenty-one randomized controlled trials and two meta-analyses. Evidence on first-line treatment found infusional 5-fu/fa/oxaliplatin (folfox) to be superior to bolus 5-fu/fa/irinotecan (ifl) for rates of median survival and tumour response, with lower incidences of most adverse effects except peripheral neuropathy. For second-line treatment after fluoropyrimidine monotherapy, folfox is a reasonable alternative for patients with contraindications to second-line irinotecan. After progression on infusional 5-fu/fa/irinotecan (folfiri), folfox is the preferred therapy. Evidence from a single randomized trial suggests that additional benefits can be expected with the addition of bevacizumab to the folfox regimen in second-line treatment. These recommendations apply to adult patients with advanced colorectal cancer who have high performance status (Eastern Cooperative Oncology Group score 0-2). Refer to Appendix A for available treatment options and to Appendix b for recommended dosages and schedules. The folfox regimen is an important component of therapy for advanced colorectal cancer. FIRST-LINE THERAPY: In one trial, folfox was shown to be superior to ifl. The folfox regimen has superior rates of median survival and tumour response. Compared with ifl, folfox has lower incidences of severe nausea, vomiting, diarrhea, and febrile neutropenia, but a higher incidence of peripheral neuropathy. Short-term infusional 5-fu/fa in combination with either oxaliplatin (folfox) or irinotecan (folfiri) are both acceptable alternatives for fit patients when combination therapy is the preferred treatment. Choice of first-line therapy may rely on patient factors and preferences-for example, less neuropathy with irinotecan versus less alopecia with oxaliplatin. SECOND-LINE THERAPY: After progression on first-line anti-thymidylate synthase monotherapy (for example, 5-fu/fa, capecitabine), irinotecan is standard second-line therapy. The folfox regimen is a reasonable alternative for patients with contraindications to the use of second-line irinotecan. After progression on both irinotecan and an anti-thymidylate synthase agent, folfox is the preferred therapy. Recent trials suggest that, as compared with folfox alone, folfox combined with bevacizumab provides additional survival benefits. The role of radiation therapy, either alone or in combination with chemotherapy, for locally advanced unresectable colorectal cancer is not addressed in this guideline. Use of chronomodulated regimens is a topic that intersects with the use of oxaliplatin/5-fu combinations, particularly chronomodulation of 5-fu in these combinations. Chronomodulation of oxaliplatin has not been extensively studied, and the topic of chronomodulation is beyond the scope of this guideline and is not addressed. Although data exist to support the use of bevacizumab in combination with folfox in second-line treatment, no first-line treatment data are available on which to make a recommendation.


Exploring the 'mood congruency' hypothesis of attention allocation - An eye-tracking study.
The 'mood-congruency' hypothesis of attention allocation postulates that individuals' current emotional states affect their attention allocation, such that mood-congruent stimuli take precedence over non-congruent ones. This hypothesis has been further suggested as an underlying mechanism of biased attention allocation in depression. The present research explored the mood-congruency hypothesis using a novel video-based mood elicitation procedure (MEP) and an established eye-tracking attention allocation assessment task, elaborating prior research in the field. Specifically, in Study 1 (n = 91), a video-based MEP was developed and rigorously validated. In study 2 (n = 60), participants' attention allocation to sad and happy face stimuli, each presented separately alongside neutral faces, was assessed before and after the video-based MEP, with happiness induced in one group (n = 30) while inducing sadness in the other (n = 30). In Study 1, the MEP yielded the intended modification of participants' current mood states (eliciting either sadness or happiness). Study 2 showed that while the MEP modified mood in the intended direction in both groups, replicating the results of Study 1, corresponding changes in attention allocation did not ensue in either group. A Bayesian analysis of pre-to-post mood elicitation changes in attention allocation supported this null finding. Moreover, results revealed an attention bias to happy faces across both groups and assessment points, suggestive of a trait-like positive bias in attention allocation among non-selected participants. Current results provide no evidence supporting the mood-congruency hypothesis, which suggests that (biased) attention allocation may be better conceptualized as a depressive trait, rather than a mood-congruent state.


CB1 cannabinoid receptor antagonist attenuates left ventricular hypertrophy and Akt-mediated cardiac fibrosis in experimental uremia.
Cannabinoid receptor type 1 (CB1R) plays an important role in the development of myocardial hypertrophy and fibrosis-2 pathological features of uremic cardiomyopathy. However, it remains unknown whether CB1R is involved in the pathogenesis of uremic cardiomyopathy. Here, we aimed to elucidate the role of CB1R in the development of uremic cardiomyopathy via modulation of Akt signalling. The heart size and myocardial fibrosis were evaluated by echocardiography and immunohistochemical staining, respectively, in 5/6 nephrectomy chronic kidney disease (CKD) mice treated with a CB1R antagonist. CB1R and fibrosis marker expression levels were determined by immunoblotting in H9c2 cells exposed to the uremic toxin indoxyl sulfate (IS), with an organic anion transporter 1 inhibitor or a CB1R antagonist or agonist. Akt phosphorylation was also assessed to examine the signaling pathways downstream of CB1R activation induced by IS in H9c2 cells. CKD mice exhibited marked left ventricular hypertrophy and myocardial fibrosis, which were reversed by treatment with the CB1R antagonist. CB1R, collagen I, transforming growth factor (TGF)-β, and α-smooth muscle actin (SMA) expression showed time- and dose-dependent upregulation in H9c2 cells treated with IS. The inhibition of CB1R by either CB1R antagonist or small interfering RNA-mediated knockdown attenuated the expression of collagen I, TGF-β, and α-SMA in IS-treated H9c2 cells, while Akt phosphorylation was enhanced by CB1R agonist and abrogated by CB1R antagonist in these cells. In summary, we conclude that CB1R blockade attenuates LVH and Akt-mediated cardiac fibrosis in a CKD mouse model. Uremic toxin IS stimulates the expression of CB1R and fibrotic markers and CB1R inhibition exerts anti-fibrotic effects via modulation of Akt signaling in H9c2 myofibroblasts. Therefore, the development of drugs targeting CB1R may have therapeutic potential in the treatment of uremic cardiomyopathy.


[Immunogenetic predisposition to chronic nonspecific inflammatory bowel disease].
Immunology has grown beyond the classic doctrine of immunity to infectious diseases, and gradually covered the problems of general physiology and pathology, genetics, embryology, transplantation, oncology and many other disciplines. A new direction has appeared--immunogenetics, which should help to answer questions the disposition and/or resistance to disease, as well as influence of environmental factors on implementation of predisposition to the development of pathology. Much attention is paid to investigation of HLA in IBD. These data indicate a significant polymorphism of major histocompatibility complex antigens in this disease in different countries. The aim of our study was to investigate the immunogenetic susceptibility and resistance to the development of ulcerative colitis (UC), and Crohn's disease (CD), the character of their flow, as well as the associated extraintestinal manifestations, in particular predisposition development of bronchial obstruction (BO) in patients with inflammatory bowel disease (IBD). A study of DNA frozen blood samples of 75 patients with IBD of both sexes has been conducted. The obtained results have been compared with the results of the study 1700 of samples of umbilical cord blood of newborns (apparently healthy children), born at 37-41 weeks' gestation in Moscow (control). The group of patients with UC revealed a positive association of HLA specificities-B*38, HLA-Cw*12 and HLA-DRV1*15, which can be regarded as potentially high risk of developing the disease. The presence of the specificity of HLA-DQV1*02 can be considered as a factor in resistance to the development of UC. High risk of developing Crohn's disease among residents of Moscow associated with groups of alleles of HLA B*41, HLA-B*56, HLA-Cw*05, HLA-Cw*08, HLA-DRV1*01, HLA-DRV1*11, HLA-DQV1*04, and the presence of specificity of HLA-DQV1*05 can be considered as a factor of resistance to the development of BC. High risk of developing BO in patients with IBD is associated with specificities HLA-DQB1*02, DQB1*03, DRB1*15.


Dialyzable transfer factor.
Dialyzable transfer factor, obtained from human peripheral blood leukocytes and first described by Lawrence, is being used in attempts to rectify defects in the cellular immune systems of patients with basic immunodeficiencies, chronic infectious diseases, and neoplastic diseases. Current knowledge of the chemical character of, assays for, and functional activities of transfer factor are briefly reviewed. An experimental animal model for dialyzable transfer factor involving the rhesus monkey (Macaca mulatta) and infection with the trematode Schistosoma mansoni is discussed. The results of this study suggest that in this model transfer factor may act both specifically and nonspecifically.


[Structure of the endothelium of the thoracic and abdominal aorta of intact rats studied by various methods of preparation and handling of the specimens].
By means of scanning and transmissive electron microscopy structural peculiarities of endothelium of the thoracic and abdominal parts of the intact rat aorta have been studied at various regimens of preparation and making specimens . The greatest changes endotheliocytes (EC) undergo at using immersion fixation after dissection of the aortal segments. These changes are less pronounced at immersion fixation in situ. A decreased perfusion pressure results in appearance of intimal folds and microfolds on the surface of EC. Increasing time for washing more than 1 min results in appearance of inflations and craters on the surfice of EC. For analysis by means of transmissive electron microscopy it is not necessary to remove blood completely out of the vascular bed. The most essential factor is to maintain perfusion pressure at the average systolic level in the given area of the vessel. However, to make the analysis by means of scanning electron microscopy this method is not suitable. The most optimal condition for initial stages of preparing vessels for morphological investigation is their washing for 1 min in the medium 199 with addition of heparin (10 units/ml) during no more than 1 min with a subsequent perfusive fixation in 2.5% solution of glutaraldehyde in the medium 199 no less than 5 min under the average arterial pressure in the given area of the vessel.


Cognitive intra-individual variability in breast cancer survivors: A systematic review.
Subjective and objective cognitive impairments in Breast Cancer Survivors (BCS) often do not correlate. One important contribution to the reported disparities may be the reliance on mean-based cognitive performance. Cognitive intra-individual variability (IIV) may provide important insights into these reported disparities. Cognitive IIV refers to the fluctuation in performance for an individual on either one cognitive task across a trial or dispersed across tasks within a neuropsychological test battery. The purpose of this systematic review was to search for and examine the literature on cognitive IIV in BCS. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach was used to search for all articles related to cognitive IIV in BCS. MEDLINE (via PubMed), Embase, and Scopus databases were searched using detailed search terms and strategies. Initially, 164 articles were retrieved but only 4 articles met the criteria for this systematic review. BCS differed from healthy controls in similar ways across the four studies, generally demonstrating similar performance but showing increased cognitive IIV for the more difficult tasks. Differences were enhanced later during chemotherapy. The four studies provide support for cognitive IIV as a useful measure to detect the subtle objective cognitive change often reported by BCS but frequently not detected by standard normed-based cognitive testing. Unexpectedly, measures of cognitive IIV were not consistently associated with self-reported measures of cognition.


[Diagnosis of maternal and infant health in Palestine].
To describe the health situation of the target population (women between 15 and 45 and children from 0 to 3), living in the towns on the West Bank in which the 12 dispensaries of the Palestine NGO Health Services Council were located, in order to plan a programme of support activities for that NGO. Crossover survey. Descriptive analysis of the data. 12 towns in the 5 districts of the West Bank (Palestine) between May and July 1994. Women of a fertile age (15 to 45) and children between 0 and 3 living in the towns where the 12 dispensaries of the NGO Health Services Council were located. Social, demographic and health variables of the population group involved, the availability of primary care services and the pattern of health service use were studied. Worthy of mention were the average fertility of fertile women of 4.55 deliveries (CI 95%, 4.30-4.80), the use of family planning methods by 61% of the women surveyed, the low indices of mother and infant malnutrition, and the frequency of episodes of acute respiratory infections and diarrhoea in the under-3s. The availability of health services in these communities is wide. The non-governmental and private Palestinian services were preferred for antenatal control, whereas the Israeli government services were preferred for deliveries, as these services had more resources. The findings were typical of an intermediately developed society, similar to neighbouring countries. The multiplicity of health services available and their lack of coordination could make the application of a unitary health policy in the area difficult.


Resistance to cytotoxic and anti-angiogenic anticancer agents: similarities and differences.
Intrinsic resistance to anticancer drugs, or resistance developed during chemotherapy, remains a major obstacle to successful treatment. This is the case both for resistance to cytotoxic agents, directed at malignant cells, and for resistance to anti-angiogenic agents, directed at non-malignant endothelial cells. In this review, we will discuss mechanisms of resistance which have a bearing on both these conceptually different classes of drugs. The complexity of drug resistance, involving drug transporters, such as P-glycoprotein, as well as resistance related to the tissue structure of solid tumors and its consequences for drug delivery is discussed. Possible mechanisms of resistance to endothelial cell-targeted drugs, including inhibitors of the VEGF receptor and EGF receptor family, are reviewed. The resistance of cancer cells as well as endothelial cells related to anti-apoptotic signaling events initiated by cell integrin-matrix interactions is discussed. Current strategies to overcome resistance mechanisms are summarized; they include high-dose chemotherapy, tumor targeting of cytotoxics to improve tumor uptake, low-dose protracted (metronomic) chemotherapy and combinations of classical agents with anti-angiogenic agents. This review discusses primarily literature published in 2001 and 2002.


Outbreak of Mycobacterium bovis in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques.
We describe a tuberculosis outbreak caused by Mycobacterium bovis in a conditioned colony of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques. Animals in five rooms were exposed, but most (16/27) infections were confined to the room that housed a mixed population of cynomolgus and rhesus macaques. In this room, rhesus (8/8) and cynomolgus (10/11) macaques naturally exposed to M. bovis were infected at nearly identical rates (Fisher exact test, 2-tailed P = 1). The clinical signs of disease and pathologic lesions in infected macaques, however, were moderately different between the two species. Rhesus macaques were more likely (5/8) to exhibit clinical signs of persistent coughing and inappetance, and had more severe pulmonary lesions. By contrast, clinical signs of disease were seen in only 1 of 19 cynomolgus macaques, and overall, the pulmonary lesions were often focal and less severe, although some still had severe involvement of the lungs similar to that seen in rhesus macaques. These differences should be taken into consideration when developing or evaluating a tuberculosis-screening program. On the basis of observations made during this outbreak, we recommend that alternative screening methods such as the PRIMAGAM test and the ESAT-6 ELISA, be incorporated into the screening program to aid in the identification of infected animals.


Communication between rehabilitation staff and people with traumatic brain injury: A systematic review.
This systematic review aimed to synthesize barriers and facilitators in communicative interactions between staff and people with traumatic brain injury (TBI) in the rehabilitation context. Searches captured published evidence up to November 2022 in MEDLINE, Embase, SCOPUS, Web of Science, CINAHL, AMED, and PsycINFO. Eligible studies reported on the communicative interaction between rehabilitation staff and adults with TBI. In total, 31 studies were included in the review; including quantitative, qualitative, and mixed-methods designs. Quality assessment was carried out using standard checklists. Quantitative studies and quantitative components of mixed-method studies were synthesized descriptively according to reported communication barriers and facilitators. Qualitative studies and qualitative components of mixed-method studies were analysed through an inductive thematic meta-synthesis; generating six main themes with four subthemes. Themes were categorized as barriers or facilitators to communicative interaction. Findings demonstrated that cognitive-communication disorders of people with TBI challenge the communicative interaction between rehabilitation staff and people with TBI. However, the extent to which these disorders create a communicative barrier is closely related to staff's communicative approach. While staff holding a collaborative and acknowledging approach and using supportive strategies may facilitate successful communicative interactions, staff using the opposite approach may exacerbate communication barriers.


Industrial support of university research in biotechnology.
A 1984 study of biotechnology companies reveals that nearly one-half of all such firms fund research in universities. Industry may support as much as one-quarter of all biotechnology research in institutions of higher education. These investments seem to be yielding substantial benefits to involved firms. Per dollar invested, university research is generating more patent applications than is other company research. Research relationships do pose some risks to traditional university values such as openness of communication among scholars. These risks may be greater in relationships involving small firms. The data also reveal that government is now, and seems likely to remain, the principal source of support for university research in biotechnology.


Transparency When Things Go Wrong: Physician Attitudes About Reporting Medical Errors to Patients, Peers, and Institutions.
Transparent communication after medical error includes disclosing the mistake to the patient, discussing the event with colleagues, and reporting to the institution. Little is known about whether attitudes about these transparency practices are related. Understanding these relationships could inform educational and organizational strategies to promote transparency. We analyzed responses of 3038 US and Canadian physicians to a medical error communication survey. We used bivariate correlations, principal components analysis, and linear regression to determine whether and how physician attitudes about transparent communication with patients, peers, and the institution after error were related. Physician attitudes about disclosing errors to patients, peers, and institutions were correlated (all P's < 0.001) and represented 2 principal components analysis factors, namely, communication with patients and communication with peers/institution. Predictors of attitudes supporting transparent communication with patients and peers/institution included female sex, US (vs Canadian) doctors, academic (vs private) practice, the belief that disclosure decreased likelihood of litigation, and the belief that system changes occur after error reporting. In addition, younger physicians, surgeons, and those with previous experience disclosing a serious error were more likely to agree with disclosure to patients. In comparison, doctors who believed that disclosure would decrease patient trust were less likely to agree with error disclosure to patients. Previous disclosure education was associated with attitudes supporting greater transparency with peers/institution. Physician attitudes about discussing errors with patients, colleagues, and institutions are related. Several predictors of transparency affect all 3 practices and are potentially modifiable by educational and institutional strategies.


Regulation of MMP-9 (type IV collagenase) production and invasiveness in gliomas by the extracellular signal-regulated kinase and jun amino-terminal kinase signaling cascades.
Our previous studies have shown that MMP-9 levels are significantly elevated during the progression of human gliomas. In the current study, we examined the role of JNK- and ERK-dependent signaling modules in the regulation of MMP-9 production and the invasive behavior of the human glioblastoma cell line SNB19, in which JNK/ERK1 is constitutively activated. SNB19 cells that were transfected with dominant-negative JNK, MEKK, and ERK1 expression vectors showed reduced MMP-9 promoter activity. In addition, conditioned medium collected from SNB19 cells transfected with these expression vectors showed diminished MMP-9 activity in the presence of phorbol myristate acetate, as determined by gelatin zymography. The cotransfection of SNB19 cells with kinase-deficient c-raf also diminished MMP-9 promoter activity. Further, in the presence of a specific inhibitor of MEKK (PD098059), the Matrigel invasion assay showed the invasiveness of dominant-negative SNB19 cells transfected with dominant-negative JNK1 or ERK1 to be remarkably reduced. In conclusion, our studies showed for the first time that MMP-9 production and the invasive behavior of SNB 19 cells are regulated by JNK- and ERK-dependent signaling modules and that interfering with either of the pathways reduces invasiveness.


A host factor absent from Lactococcus lactis subspecies lactis MG1363 is required for conjugative transposition.
In matings between Lactococcus lactis strains, the conjugative transposons Tn916 and Tn919 are found in the chromosome of the transconjugants in the same place as in the chromosome of the donor, indicating that no transposition has occurred. In agreement with this, the frequency of L. lactis transconjugants from intraspecies matings is the same whether the donor contains the wild-type form of the transposon or the mutant Tn916-int1, which has an insertion in the transposon's integrase gene. However, in intergeneric crosses with Bacillus subtilis or Enterococcus faecalis donors, Tn916 and Tn919 transpose to different locations on the chromosome of the L. lactis transconjugants. Moreover, Tn916 and Tn919 could not be transferred by conjugation from L. lactis and B. subtilis, E. faecalis or Streptococcus pyogenes. This suggests that excision of these elements does not occur in L. lactis. When cloned into E. coli with adjacent chromosomal DNA from L. lactis, the conjugative transposons were able to excise, transpose and promote conjugation. Therefore, the inability of these elements to excise in L. lactis is not caused by a permanent structural alteration in the transposon. We conclude that L. lactis lacks a factor required for excision of conjugative transposons.


mcr Genes Conferring Colistin Resistance in Enterobacterales; a Five Year Overview.
The present review aims to study and detect the global emergence of mcr genes in E. coli, K. pneumoniae and Salmonella spp., isolates from human specimens over the last six years. Nowadays the rise of multidrug-resistant superbugs has made essential the return of drugs that were previously abandoned. A clear example is colistin, which acts against multidrug - resistant gram - negative pathogens, including Enterobacterales. Colistin resistance is an unfortunate fact, with the emergence of mcr genes conferring resistance to colistin in Enterobacterales posing the most recent threat. Literature about mcr genes and their spread in E. coli, K. pneumoniae and Salmonella spp. is cited, focusing on the emergence of mcr genes in human specimens since 2015. The data were taken from the PubMed and Scopus databases. It seems that the mcr-1 gene continues to be the protagonist among the three species. E. coli is the dominant species harbouring mcr genes. Moreover, plasmid - mediated colistin resistance is also conferred upon other species that carry different genes resistant to antibiotics. There are only scarse reports on human Salmonella spp isolates harbouring mcr genes. Finally, the emergence of the mcr-9 gene in all of them is quite remarkable. CONCLUSION: Plasmid - mediated colistin resistance in Enterobacterales is a global issue and has been worsening over the years. The continuous mutations of mcr gene subtypes underline the need for better surveillance, constant investigation and wise use of colistin, especially in countries with high levels of antibiotic resistance.


Automatic Chinese Food recognition based on a stacking fusion model.
With commercialization of deep learning models, daily precision dietary record based on images from smartphones becomes possible. This study took advantage of Deep-learning techniques on visual recognition tasks and proposed a big-data-driven Deep-learning model regressing from food images. We established the largest data set of Chinese dishes to date, named CNFOOD-241. It contained more than 190,000 images with 241 categories, covering Staple food, meat, vegetarian diet, mixed meat and vegetables, soups, dessert category. This study also compares the prediction results of three popular deep learning models on this dataset, ResNeXt101_32x32d achieving up to 82.05% for top-1 accuracy and 97.13% for top-5 accuracy. Besides, this paper uses a multi-model fusion method based on stacking in the field of food recognition for the first time. We built a meta-learner after the base model to integrate the three base models of different architectures to improve robustness. The accuracy achieves 82.88% for top-1 accuracy.Clinical Relevance-This study proves that the application of artificial intelligence technology in the identification of Chinese dishes is feasible, which can play a positive role in people who need to control their diet, such as diabetes and obesity.


Acidification effects on isolation of extracellular vesicles from bovine milk.
Bovine milk extracellular vesicles (EVs) attract research interest as carriers of biologically active cargo including miRNA from donor to recipient cells to facilitate intercellular communication. Since toxicity of edible milk seems to be negligible, milk EVs are applicable to use for therapeutics in human medicine. Casein separation is an important step in obtaining pure EVs from milk, and recent studies reported that adding hydrochloric acid (HCl) and acetic acid (AA) to milk accelerates casein aggregation and precipitation to facilitate EV isolation and purification; however, the effects of acidification on EVs remain unclear. In this study, we evaluated the acidification effects on milk-derived EVs with that by standard ultracentrifugation (UC). We separated casein from milk by either UC method or treatment with HCl or AA, followed by evaluation of EVs in milk serum (whey) by transmission electron microcopy (TEM), spectrophotometry, and tunable resistive pulse sensing analysis to determine EVs morphology, protein concentration, and EVs size and concentration, respectively. Moreover, we used anti-CD9, -CD63, -CD81, -MFG-E8, -HSP70, and -Alix antibodies for the detection of EVs surface and internal marker proteins by western blot (WB). Morphological features of EVs were spherical shape and similar structure was observed in isolated EVs by TEM. However, some of the EVs isolated by HCl and AA had shown rough surface. Although protein concentration was higher in whey obtained by UC, EV concentration was significantly higher in whey following acid treatment. Moreover, although all of the targeted EVs-marker-proteins were detected by WB, HCl- or AA-treatments partially degraded CD9 and CD81. These findings indicated that acid treatment successfully separated casein from milk to allow efficient EV isolation and purification but resulted in partial degradation of EV-surface proteins. Our results suggest that following acid treatment, appropriate EV-surface-marker antibodies should be used for accurate assess the obtained EVs for downstream applications. This study describes the acidification effects on EVs isolated from bovine milk for the first time.


Gene expression in amygdala as a function of differential trait anxiety levels in genetically heterogeneous NIH-HS rats.
To identify genes involved in anxiety/fear traits, we analyzed the gene expression profile in the amygdala of genetically heterogeneous NIH-HS rats. The NIH-HS rat stock has revealed to be a unique genetic resource for the fine mapping of Quantitative Trait Loci (QTLs) to very small genomic regions, due to the high amount of genetic recombinants accumulated along more than 50 breeding generations, and for the same reason it can be expected that those genetically heterogeneous rats should be especially useful for studying differential gene expression as a function of anxiety-(or other)-related traits. We selected high- and low-anxious NIH-HS rats differing in their number of avoidances in a single 50-trial session of the two-way active avoidance task. Rats were also tested in unconditioned anxiety tests (e.g., elevated zero-maze). Three weeks after behavioural testing, the amygdala was dissected and prepared for the microarray study. There appeared 6 significantly down-regulated and 28 up-regulated genes (fold-change >|2|, FDR<0.05) between the low- and high-anxious groups, with central nervous system-related functions. Regression analyses (stepwise) revealed that differential expression of some genes could be predictive of anxiety/fear responses. Among those genes for which the present results suggest a link with individual differences in trait anxiety, six relevant genes were examined with qRT-PCR, four of which (Ucn3, Tacr3, H2-M9 and Arr3) were validated. Remarkably, some of them are characterized by sharing known functions related with hormonal HPA-axis responses to (and/or modulation of) stress, anxiety or fear, and putative involvement in related neurobehavioural functions. The results confirm the usefulness of NIH-HS rats as a good animal model for research on the neurogenetic basis of anxiety and fear, while suggesting the involvement of some neuropeptide/neuroendocrine pathways on the development of differential anxiety profiles.


[Importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired pneumonia].
To determine the importance of Mycoplasma pneumoniae and Chlamydia pneumoniae in community-acquired pneumonia (CAP) of children from different latitudes and to compare clinical outcome using azithromycin (AZM) versus either amoxicillin-clavulanate (A-C) or erythromycin estolate (EE). Ambulatory patients with CAP were identified at either the Children's Medical Center of Dallas, Texas or the Hospital del Niño of Panama City, Panama. Children 6 months to 15 years of age were enrolled and randomized to receive either AZM for 5 days or a 10 day course of either A-C or EE, for those younger or older than 5 years of age, respectively. Mycoplasma pneumoniae and C. pneumoniae were identified by measuring acute and convalescent serum antibody titers and by performing nasopharyngeal (NP) and oropharyngeal (OP) swabs for culture and polymerase chain reaction (PCR) testing. Overall 335 patients (168 in Dallas and 167 in Panama) were evaluated from February 1996 through December 1997. Acute M. pneumoniae infection was detected in 12 (7%) patients each in Dallas and Panama. Acute C. pneumoniae infection was observed in 10 (6%) children at each site. Infection caused by these "atypical" microorganisms occurred more frequently in children older than 5 years of age (23% vs 9%, P = 0.001, RR 2.5, 95% CI 1.4-4.3). No distinctive pattern of clinical or radiologic abnormalities was seen in relation to etiology. Clinical cure was achieved in 43 of 44 children infected by these bacteria regardless of treatment assignment. Mycoplasma pneumoniae and C. pneumoniae are common etiologic agents of CAP in older children from different latitudes. Children with CAP present with similar clinical and radiologic findings to those caused by other etiologic agents. Outcome was excellent for the three treatment regimens studied.


Phenolic Acid Derivatives from Ficus esquiroliana Levl. and Their Anti-Inflammatory Effects.
One new mesomer, ficusnaph A (1), two new phenolic acid derivatives, ficusnaphs B and C (2 and 3) together with three known biogenetically related polysubstituted naphthalene derivatives (4-6) were isolated from the stems of Ficus esquiroliana Levl. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1-6 were evaluated the inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in mouse macrophage RAW264.7 cells in vitro. Compounds 1 and 2 showed significant inhibitory activity with the IC50 value of 3.12±0.14 and 7.66±0.18 μM, respectively.


Clinical and histopathological features of myofibrillar myopathy in Warmblood horses.
To report a novel exertional myopathy, myofibrillar myopathy (MFM) in Warmblood (WB) horses. To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses and 2) investigate the potential inheritance of MFM in a Warmblood family. Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10). Prospectively, muscle biopsies were obtained from controls (n = 8) and a three generation WB family (n = 11). Samples were assessed for histopathology [scored 0-3], fibre types, cytoskeletal and Z disc protein aggregates, electron microscopic alterations (EM) and muscle glycogen concentrations. Myofibrillar myopathy-affected cases experienced exercise intolerance, reluctance to go forward, stiffness and poorly localised lameness. Abnormal aggregates of the cytoskeletal protein desmin were found in up to 120 type 2a and a few type 2x myofibres of MFM cases. Desmin positive fibres did not stain for developmental myosin, α actinin or dystrophin. Scores for internalised myonuclei (score MFM 0.83 ± 0.67, controls 0.22 ± 0.45), anguloid atrophy (MFM 0.95 ± 0.55, controls 0.31 ± 0.37) and total myopathic scores (MFM 5.85 ± 2.10, controls 1.41 ± 2.17) were significantly higher in MFM cases vs. Focal Z disc degeneration, myofibrillar disruption and accumulation of irregular granular material was evident in MFM cases. Muscle glycogen concentrations were similar between MFM cases and controls. In the Warmblood family, desmin positive aggregates were found in myofibres of the founding dam and in horses from two subsequent generations. Restricted sample size due to limited availability of well phenotyped cases. A distinctive and potentially heritable form of MFM exists in Warmblood horses that present with exercise intolerance and abnormal hindlimb gait. Muscle tissue is characterised by ectopic accumulation of desmin and Z disc and myofibrillar degeneration.


The Incidence of Hip Fractures in Long-Term Care Homes in Saskatchewan from 2008 to 2012: an Analysis of Provincial Administrative Databases.
Hip fractures (HFs) represent an important cause of morbidity and mortality among adults in long-term care (LTC), but lack of detailed epidemiological data poses challenges to intervention planning. We aimed to determine the incidence of HFs among permanent LTC residents in Saskatchewan between 2008 and 2012, using linked, provincial administrative health databases, exploring associations between outcomes and basic individual and institutional characteristics. We utilized the Ministry of Health databases to select HF cases based on ICD 10 diagnoses fracture of head and neck of femur, pertrochanteric fracture and subtrochanteric fracture of femur. HF incidence rates in LTC were compared to older adults in the general population. LTC residents were more likely to be female overall (65.5%), although this varied by age, with only 46.6% female in those under 65, but 77% female among those 90 years and older. Mean age of residents was highest in rural centres (85.2 yrs) and lowest in medium-large centres (81.0 yrs). Of 6,230 cases of HFs in the province during the study period, 2,743 (44%) were in the LTC cohort. Incidence rates per 1,000 person years increased with age and were higher in the LTC group (F = 68.6, M = 49.8) than the overall population (F = 1.62, M = 0.73). Rates of HFs in the province and in LTC were higher in females than males in all age groups, except for the youngest (< 65 years), where males had higher rates, and the oldest category (90+) where rates were similar. Women 90+ years in larger LTC had significantly higher (p = .035) HF rates than those in smaller LTC, and also had significantly (p = .001) higher rates in medium-large compared to smaller population centres. However, after age standardization to the overall SK population, it was apparent that the larger LTC facilities and the medium-large population centres had overall lower HF rates than the small and medium LTC facilities and the small urban and rural PCs, respectively. One health region had particularly high rates, even when accounting for age and sex composition. Both HF numbers and incidence rates were higher in LTC compared to the overall population, with higher rates in older women, small to medium size LTC, and particular health regions. Our data suggest the need for further exploration of potentially remediable factors for HFs in smaller LTCs, and for targeting specific facilities and regions with outlying HF rates.


Spring coil retraction in coil occlusion of persistent ductus arteriosus.
To present the short and intermediate term results of coil occlusion of persistent ductus arteriosus and the results of radiographic measurements of spring coils implanted to treat patent ducts. 22 children underwent coil occlusion. Their ages ranged from 2 years 9 months to 12 years 10 months (mean (SD) age, 6.5 (3.6) years). The duct diameter ranged from 1.0 to 3.5 mm at the narrowest point (mean 2.6 (0.7) mm). In 11 of the children regular coils were implanted using the non-attached system, while in the other 11 the detachable coil embolisation system was used. 12 children (55%) had no significant residual leaks immediately after procedures involving a single coil delivery. The remaining 10 (45%) had residual leaks immediately after the procedure, although no patient with a large duct showed residual leakage 18 months after the procedure. Radiographic measurement of the coils showed that all implanted coils retracted to 65-85% of their original size immediately after occlusion. This retraction was more evident in patients showing spontaneous closure of the residual shunt or having a coil 8 mm in diameter. Coil embolisation is an acceptable method for occluding persistent ductus arteriosus. Retraction of implanted coils is common in the follow up period. Such retraction may be related to spontaneous closure of residual shunt after embolisation.


Long-term follow-up of transsexual persons undergoing sex reassignment surgery: cohort study in Sweden.
The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person's body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment. To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons. A population-based matched cohort study. Sweden, 1973-2003. All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973-2003. Random population controls (10:1) were matched by birth year and birth sex or reassigned (final) sex, respectively. Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]). The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8-4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8-62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9-8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0-3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls. Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group.


Considering responsivity: a proposal for pragmatic analysis in autism spectrum.
To compare the pragmatic profile referring to the communicative initiatives and the bi-dimensional profile involving the aspects of initiative and responsivity. It also aimed to analyze the most common types of responses presented by the studied individuals. Thirty recorded samples of interaction between speech-language therapist and children with autism spectrum disorders (mean age: 9 years and 6 months) sessions were analyzed. The samples were transcribed and data analyzed about number of communicative acts, occupation of the communicative space, use of communicative means (verbal, vocal and gestural) and total number of participations (initiatives and responses). The responses were qualified as "non-answer", "adequate answer", "inadequate answer" and "pragmatically inappropriate answer". Significant differences in the comparison of the numbers of initiatives and total participations and of occupation of communicative space and total number of communicative acts. There was also a significant difference in the number of "adequate answers". Results show the need to consider the bi-dimensional communicative profile and qualify the answers in order to determine the child's communication abilities.


Persistent high fertility in Uganda: young people recount obstacles and enabling factors to use of contraceptives.
High fertility among young people aged 15-24 years is a public health concern in Uganda. Unwanted pregnancy, unsafe induced abortions and associated high morbidity and mortality among young women may be attributed to low contraceptive use. This study aims at exploring reasons for low contraceptive use among young people. In 16 focus group discussions, the views of young people about obstacles and enabling factors to contraceptive use in Mityana and Mubende districts, Uganda were explored. The groups were homogeneously composed by married and unmarried men and women, between the ages of 15-24. The data obtained was analyzed using qualitative content analysis. Young men and women described multiple obstacles to contraceptive use. The obstacles were categorized as misconceptions and fears related to contraception, gender power relations, socio-cultural expectations and contradictions, short term planning, and health service barriers. Additionally, young people recounted several enabling factors that included female strategies to overcome obstacles, changing perceptions to contraceptive use, and changing attitude towards a small family size. Our findings suggest changing perceptions and behavior shift towards contraceptive use and a small family size although obstacles still exist. Personalized strategies to young women and men are needed to motivate and assist young people plan their future families, adopt and sustain use of contraceptives. Reducing obstacles and reinforcing enabling factors through education, culturally sensitive behavior change strategies have the potential to enhance contraceptives use. Alternative models of contraceptive service delivery to young people are proposed.