Efficacy of Etimicin Sulfate Combined with Cefotaxime Sodium in the Treatment of Patients with Septic Shock and Effect on Serum Inflammatory Factor Levels and Immune Function.
To explore the effect of etimicin sulfate combined with cefotaxime sodium and cefotaxime sodium alone in the treatment of patients with septic shock and the effect on serum inflammatory factor levels and immune function. Total of 95 patients with septic shock who were treated in our hospital from March 2018 to July 2020 were collected as the subjects of this study. Among them, 44 patients who received cefotaxime sodium treatment and were included in the control group, and 51 patients who received etimicin sulfate combined with cefotaxime sodium treatment were included in the research group. The levels of serum IL-6 (interleukin-6), PCT (procalcitonin), TNF-α (tumor necrosis factor-α), CD3+ (cluster of differentiation 3+), CD4+, CD4+/CD8+, FIB (fibrinogen), and PT (prothrombin time), APTT (activated partial thromboplastin time) time before and after treatment, and the treatment effects, mechanical ventilation time, hospitalization time, and incidence of adverse reactions between the two groups were compared. The total effective rate of treatment in the research group (90.20%) was higher than the control group (72.73%) (p < 0.05). After treatment, the serum levels of IL-6, PCT, and TNF-α, FIB, CD3+, CD4+, CD4+/CD8+, and PT and APTT time in the two groups of patients have improved significantly (p < 0.05). Compared with the control group, the research group's IL-6, PCT, TNF-α levels, PT, and APTT decreased more, and FIB, CD3+, CD4+, and CD4+/CD8+ levels increased more (p < 0.05). The mechanical ventilation time and hospital stay of the research group were significantly shorter than the control group (p < 0.05). There was no significant difference between the total incidence of adverse reactions in the research group (15.69%) and the control group (9.09%) (p > 0.05). Compared with cefotaxime sodium alone, the treatment of etimicin sulfate combined with cefotaxime sodium is more effective in improving the coagulation function and cellular immune function of patients with septic shock, reducing the level of serum inflammatory factors, and having higher clinical treatment effective.


Increased energy intake and a shift towards high-fat, non-staple high-carbohydrate foods amongst China's older adults, 1991-2009.
We examined trends from 1991-2009 in total energy intake and food group intake, and examine whether shifts varied by age or generation. Longitudinal time series (1991, 1993, 1997, 2000, 2004, 2006, 2009). Nine provinces in China. Older Chinese aged ≥60 years (n=5,068) from the China Health and Nutrition Survey from 1991-2009. Using three 24-hour recalls and a household food inventory collected over three consecutive days, the top twenty food group contributors to total energy intake from 1991-2009 were identified, and the mean kilocalorie (kcal) difference between 1991 and 2009 for each food group was ranked. The top twenty food group contributors to total energy intake from 1991-2009 were identified, and the mean kilocalorie (kcal) difference between 1991 and 2009 for each food group was ranked. Linear regression was used to examine changes in mean calorie intake of food groups between 1991 and 2009, adjusting for age, sex, and region. In addition, we examined changes in the mean kcal per capita intake to examine shifts by age group and generation. Mean total energy intake increased significantly among older Chinese adults from 1379 total kilocalories in 1991 to 1463 kilocalories in 2009 (p< 0.001). Most food groups showed a significant increase in intake from 1991 to 2009, with plant oil, wheat buns, and wheat noodles showing the greatest increase. At the same age, more recent generations had more energy intake than earlier generations. An aging effect was observed, with energy intake decreasing with age, although more recent generations showed a smaller decrease in energy intake with aging. Older Chinese adults in recent generations show an increase in total calorie intake compared to older Chinese of earlier generations, paired with a less significant decrease in calorie intake as they age. Increased consumption of high-fat, non-staple high-carbohydrate foods such as plant oil and wheat buns suggests that diet quality of older Chinese adults is becoming less healthful in recent years.


Effect of escitalopram on an acetic acid-induced ulcerative colitis model.
Ulcerative colitis (UC) is a chronic and recurrent gastrointestinal (GI) disorder with an unknown aetiology and pathogenesis. Regarding the effectiveness of antidepressants on UC in animal models of depression and the known anti-inflammatory effects of escitalopram this study was conducted to evaluate the beneficial effects of escitalopram on an acetic acid-induced UC model without depression. UC model was induced by intra rectal (i.r.) administration of 4% acetic acid in rats after 24 hours of fasting. Animals were treated with three doses of escitalopram (5, 10 and 20 mg/kg). Prednisolone (4 mg/kg) was used as a reference drug in UC. Histological and oxidative stress markers were measured in all groups. Results showed significant increase in superoxide dismutase (SOD) activity and glutathione (GSH) levels, as well as significant decrease in myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, macroscopic factors (ulcer surface area, ulcer severity and weight-to-colon ratio) and microscopic and histological parameters (severity and extent of inflammation, cryptic destruction and severity of tissue involvement) in escitalopram treated rats (10, 20 mg/kg) compared to the UC group. In conclusion, the results of our study are in support of beneficial anti-inflammatory and antioxidant effects of escitalopram in UC.


MR imaging of the yucatan pig head and neck vasculature.
To evaluate the cerebral venous drainage system of the swine as a probable model to test whether extracranial venous abnormalities may play a role in neurodegenerative diseases as reported recently in multiple sclerosis. Three Yucatan micropigs, 5 to 7 months old, were scanned with a comprehensive MRI protocol at 3 Tesla. The vascular anatomy of the head and neck was imaged using conventional and angiographic MR sequences. Phase-contrast MR images were collected at multiple levels of the neck and intracranial space to monitor flow. Three large cervical veins were observed; the external jugular vein draining the olfactory and gustatory tissues; the internal jugular vein (IJV) draining the cavernous sinus as well as surrounding soft tissues in the neck; and the ventral vertebral venous plexus (VVVP) surrounding the dural sac and paraspinal region. The majority of the cerebral blood flow in the pig appears to drain through the VVVP. Flow through the IJV comprised a nondominant component. Anastamoses were observed connecting the major veins of the neck bilaterally. The dominance of outflow from the brain to the VVVP may be analogous to the typical dominance of the IJVs in humans in the supine position.


[Component communities of the parasites of gudgeon (Gobio gobio) from the basins of Northern Dvina and Mezen rivers].
Component communities of parasites of gudgeon from the ecologically sustainable reservoirs are studied. The general principle of their organization is established. The material had been collected in the basins of Northern Dvina (41 specimens of gudgeon were dissected) and Mezen (55 specimens of gudgeon were dissected) rivers using generally accepted methods. Errors of regression equations for all individual species groups with their subsequent summation were calculate in order to estimate the state of the component community structure. In different seasons of a year the component community of the parasites of gudgeon from the Ertom river has the same structure, which is determined by the ratio of the biomasses of its comprising species, while it is differs in its species composition, biomasses of the species, leading groups of parasites, and in the dominating species. Thus, several stable seasonal states of the communities of fish parasites can be supposed. Three groups of species distinguished by the ratio of their biomasses are the general for the component communities of the parasites of gudgeon from the basins of Northern Dvina and Mezen rivers. The generalist species is more frequently the dominating species. The group of autogenic species always leads in the community. When methods of parasites collection are violated, the decrease in the number of species groups down to two is recorded. When the materials collected in different periods of a year from an ecologically sustainable reservoir are mixed, the sum of the errors of regression equations become higher than 0.250.


Learning on dynamic statistical manifolds.
Hyperbolic balance laws with uncertain (random) parameters and inputs are ubiquitous in science and engineering. Quantification of uncertainty in predictions derived from such laws, and reduction of predictive uncertainty via data assimilation, remain an open challenge. That is due to nonlinearity of governing equations, whose solutions are highly non-Gaussian and often discontinuous. To ameliorate these issues in a computationally efficient way, we use the method of distributions, which here takes the form of a deterministic equation for spatio-temporal evolution of the cumulative distribution function (CDF) of the random system state, as a means of forward uncertainty propagation. Uncertainty reduction is achieved by recasting the standard loss function, i.e. discrepancy between observations and model predictions, in distributional terms. This step exploits the equivalence between minimization of the square error discrepancy and the Kullback-Leibler divergence. The loss function is regularized by adding a Lagrangian constraint enforcing fulfilment of the CDF equation. Minimization is performed sequentially, progressively updating the parameters of the CDF equation as more measurements are assimilated.


Medicine, merit, money and caste: the complexity of medical education in India.
Private medical colleges in India are under the scanner. There is a longstanding debate about the selection methodology that should be followed for admissions in medical colleges. A significant proportion of aspirants are able to afford medical education in private colleges despite not clearing entrance examinations. Others gain entry purely on the basis of caste. Medicine deals with human life and, consequently, there is a widespread feeling that admission criteria in medical schools should be based only on merit as assessed in entrance examinations. This article examines some of these contentious issues.


Predicting pathologic tumor response to chemoradiotherapy with histogram distances characterizing longitudinal changes in 18F-FDG uptake patterns.
A family of fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) features based on histogram distances is proposed for predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT). These features describe the longitudinal change of FDG uptake distribution within a tumor. Twenty patients with esophageal cancer treated with CRT plus surgery were included in this study. All patients underwent PET/CT scans before (pre-) and after (post-) CRT. The two scans were first rigidly registered, and the original tumor sites were then manually delineated on the pre-PET/CT by an experienced nuclear medicine physician. Two histograms representing the FDG uptake distribution were extracted from the pre- and the registered post-PET images, respectively, both within the delineated tumor. Distances between the two histograms quantify longitudinal changes in FDG uptake distribution resulting from CRT, and thus are potential predictors of tumor response. A total of 19 histogram distances were examined and compared to both traditional PET response measures and Haralick texture features. Receiver operating characteristic analyses and Mann-Whitney U test were performed to assess their predictive ability. Among all tested histogram distances, seven bin-to-bin and seven crossbin distances outperformed traditional PET response measures using maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC = 0.80). The seven bin-to-bin distances were: L(2) distance (AUC = 0.84), χ(2) distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC = 0.83), squared Euclidean distance (AUC = 0.83), L(1) distance (AUC = 0.82), and Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov distance (AUC = 0.88), quadratic form distance (AUC = 0.87), and match distance (AUC = 0.84). These crossbin histogram distance features showed slightly higher prediction accuracy than texture features on post-PET images. The results suggest that longitudinal patterns in (18)F-FDG uptake characterized using histogram distances provide useful information for predicting the pathologic response of esophageal cancer to CRT.


Do dental stem cells depict distinct characteristics? - Establishing their "phenotypic fingerprint".
Dental tissues provide an alternate source of stem cells compared with bone marrow and have a similar potency as that of bone marrow derived mesenchymal stem cells. It has been established there are six types of dental stem cells: Dental pulp stem cells, stem cells from human exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, dental follicle progenitor cells, oral periosteum stem cells and recently gingival connective tissue stem cells. Most of the dental tissues have a common developmental pathway; thus, it is relevant to understand whether stem cells derived from these closely related tissues are programmed differently. The present review analyzes whether stem cells form dental tissues depict distinct characteristics by gaining insight into differences in their immunophenotype. In addition, to explore the possibility of establishing a unique phenotypic fingerprint of these stem cells by identifying the unique markers that can be used to isolate these stem cells. This, in future will help in developing better techniques and markers for identification and utilization of these stem cells for regenerative therapy.


Trevo 2000: Results of a Large Real-World Registry for Stent Retriever for Acute Ischemic Stroke.
Background Recent randomized controlled trials show benefit of thrombectomy for large vessel occlusion in stroke. Real-world data aid in assessing reproducibility of outcomes outside of clinical trials. The Trevo Retriever Registry is a multicenter, international, prospective study designed to assess outcomes in a large cohort of patients. Methods and Results The Trevo Registry is a prospective database of patients with large vessel occlusion treated with the Trevo device as the first device. The primary end point is revascularization based on modified Thrombolysis in Cerebral Infarction score and secondary end points include 90-day modified Rankin Scale, 90-day mortality, neurological deterioration at 24 hours, and device/procedure related adverse events. Year 2008 patients were enrolled at 76 centers in 12 countries. Median admission National Institutes of Health Stroke Scale was 16 (interquartile range, 11-20). Occlusion sites were internal carotid artery (17.8%), middle cerebral artery (73.5%), posterior circulation (7.1%), and distal vascular locations (1.6%). A modified Thrombolysis in Cerebral Infarction 2b or 3 was achieved in 92.8% (95% CI, 91.6, 93.9) of procedures, with 55.3% (95% CI, 53.1, 57.5) of patients achieving modified Rankin Scale ≤2 at 3 months. Patients meeting revised 2015 American Heart Association criteria for thrombectomy had a 59.7% (95% CI , 56.0; 63.4) modified Rankin Scale 0 to 2 at 3 months, whereas 51.4% treated outside of American Heart Association criteria had modified Rankin Scale 0 to 2. 51.4% (95% CI , 49.6, 55.4). Symptomatic intracranial hemorrhage rate was 1.7% (95% CI , 1.2, 2.4). Conclusions The Trevo Retriever Registry represents real-world data with stent retriever. The registry demonstrates similar reperfusion rates and outcomes in the community compared with rigorous centrally adjudicated clinical trials. Future subgroup analysis of this cohort will assist in identifying areas of future research. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02040259.


Establishing a model for care in schizophrenia: one program's experience.
Unified service systems for the chronic mentally ill are frequently proposed yet rarely implemented. This paper presents a program developed specifically to meet the needs of young people with schizophrenia and their families. The program's evolution and design, from its origins in a hospital to its eventual base in the community, are described. The implications of a clinical teaching unit affiliated with a university are outlined. The experience of a typical patient and his family provides a view from a clinical context. Hypotheses arising from this case study point to future empirical work in the development of model programs in the care of the long term mentally ill.


The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.
The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.


Immunohistochemistry in assessment of molecular pathogenesis of cervical carcinogenesis.
Concerning the prediction of HPV-associated cervical disease, several importance issues are related both to the management of women with diagnosed CIN and those with cervical cancer. Oncogenic HPVs are capable of contributing to the development of malignant phenotype by several different mechanisms, most of which seem to be closely interrelated. Because of the fact that these molecular interactions are mediated by proteins, the logical strategy to dissect the complex molecular pathways is to study the functions of these proteins, utilising the capabilities of immunohistochemistry (IHC). IHC offers practically unlimited possibilities to study any target molecules, against which a monoclonal or polyclonal antibody can be raised. This review describes the IHC-based strategies used by this author to assess the molecular pathogenesis of cervical cancer and its precursors in a number of large-scale prospective cohort studies conducted during the past 25 years. In the ongoing HPV-PathogenISS study, 13 different markers are being tested to evaluate their predictive value in distinct viral events, e.g. persistence or clearance of high-risk HPV in women treated for CIN. Apart from getting new insights into the molecular pathogenesis of HPV-associated cervical carcinogenesis, we anticipate the disclosure of individual markers, a set of markers, or an expression profile of any such marker sets that would be of clinical value as predictors of disease outcome in cervical carcinogenesis.


Are patients with chronic low back pain or chronic neck pain fatigued?
The objectives of this study were the following: to determine if fatigue is present in chronic low back pain (LBP) and chronic neck pain patients to a greater extent than in controls (nonpatients); to determine which variables are associated with the presence of fatigue; and to determine which of the above chronic pain patient (CPP) groups is more fatigued. To the authors' knowledge, this is the first such study in the literature. Totals of 175 chronic LBP and 33 chronic neck pain patients completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale (NPS), and Beck Depression Inventory rating scales on admission. In addition, an information tool was completed on each CPP and contained the following information: demographics, primary and secondary pain diagnoses, DSM-IV psychiatric diagnoses assigned, pain location, pain precipitating event, type of injury, years in pain, number of surgeries, types of surgery, type of pain pattern, opioids consumed per day in morphine equivalents, workers' compensation status, and whether, according to the clinical examination, the pain did or did not have a neuropathic component. Scores on the MFI were then compared with published norms for controls (nonpatients) via chi-squared tests. Bivariate analyses were conducted between the MFI subscales and the variables selected for analysis. Pearson correlations, analyses of variance, and t-tests were used to test for relationships between MFI scale scores and the appropriate variables. In the next step of the analysis, stepwise regression analyses were used to predict each of the MFI subscale scores using the variables that were found to be significantly (P < 0.05) related to fatigue by the preceding analysis. In the final analysis, the variables that were significant predictors of the fatigue subscales were controlled for as covariates in an analysis of variance in order to determine if chronic LBP patients had scores on the MFI subscales that were significantly different from those of chronic neck pain patients. Multidisciplinary pain facility. Chronic LBP and chronic neck pain patients. Chronic LBP and chronic neck pain patients were found to be significantly more fatigued than controls (nonpatients). Most of the MFI subscale scores could be predicted by four major variables: presence of neuropathic pain, female gender, presence of depression, and total number of DSM-IV diagnoses. Chronic LBP patients were as fatigued as chronic neck pain patients. The complaint of fatigue appears to be a significant problem for chronic LBP and chronic neck pain patients. This complaint may be associated with neuropathic pain, female gender, and psychiatric comorbidities.


Managing endometrial calcifications using Kshara Taila and Phalaghrita Uttara Basti: A case report.
Endometrial calcification is an uncommon clinical entity. They can be detected during pelvic ultrasonography or as incidental pathologic findings. Most of the cases are asymptomatic or present with secondary infertility and menstrual anomalies. Its definite etiology is still not known and the pathogenesis is uncertain; its clinical importance is not yet fully validated. Since there is no exact simulating disease to compare this condition in Ayurveda; according to the features involved in its pathophysiology; involvement of Tridosha has been contemplated. Therefore, the management of endometrial calcifications is conducted by considering the specific Dosha involved. Uttara Basti is a minimally invasive procedure that can be easily performed as an outpatient procedure, offering a more convenient and cost-effective approach to enhance the treatment of endometrial calcifications. Here in this case study, the patient had been diagnosed with endometrial calcifications and was subsequently scheduled for an Ayurvedic management protocol. The procedure of Uttara Basti with Kshara Oil and Phala ghrita, was undertaken for a duration of 3 consecutive months, following the cessation of menstrual flow. The patient experienced improvment in scanty menses, her USG showed a reduction in endometrial calcification. Furthermore, she was conceived.


Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle.
Bacterial populations vary in their stress tolerance and population structure depending upon whether growth occurs in well-mixed or structured environments. We hypothesized that evolution in biofilms would generate greater genetic diversity than well-mixed environments and lead to different pathways of antibiotic resistance. We used experimental evolution and whole genome sequencing to test how the biofilm lifestyle influenced the rate, genetic mechanisms, and pleiotropic effects of resistance to ciprofloxacin in Acinetobacter baumannii populations. Both evolutionary dynamics and the identities of mutations differed between lifestyle. Planktonic populations experienced selective sweeps of mutations including the primary topoisomerase drug targets, whereas biofilm-adapted populations acquired mutations in regulators of efflux pumps. An overall trade-off between fitness and resistance level emerged, wherein biofilm-adapted clones were less resistant than planktonic but more fit in the absence of drug. However, biofilm populations developed collateral sensitivity to cephalosporins, demonstrating the clinical relevance of lifestyle on the evolution of resistance.


Sarcoidosis in the national veteran population: association of ocular inflammation and mortality.
To describe the distribution of ocular sarcoidosis in the veteran population and to determine the association between ocular disease and all-cause mortality. Retrospective review. The Veterans Health Administration National Patient Care Database information on medical diagnoses, date of diagnosis, age, race, gender, and Veterans Administration medical center station number for site-specific calculations for fiscal years 2010 through 2012 was collected. Mortality data were obtained from the Beneficiary Identification Records Locator Subsystem. The patient cohort was identified with a primary diagnosis of sarcoidosis using International Classification of Disease, ninth edition, code of 135 in outpatient treatment files for the study period. The sarcoidosis patients were divided into those with uveitis or orbital inflammation (defined as ocular inflammation for this study) and those without uveitis or orbital inflammation. Survival analysis was performed using the Cox proportional hazard method. Association between ocular inflammation and 1-year mortality. Of 15 130 subjects with sarcoidosis, 3364 (22.2%) were evaluated in an eye clinic within a Veterans Administration Medical Center. Most patients were diagnosed with anterior uveitis (n = 1013; 80.7% of ocular inflammation), and the least common diagnosis was orbital granuloma (n = 28; 2.2% of ocular inflammation). Male gender was protective to the development of uveitis (estimate, 0.76; 95% confidence interval, 0.65-0.88; P = 0.0005). The overall 1-year all-cause mortality for all patients with a diagnosis of sarcoidosis was 2.0%. Ocular inflammation was associated with a decrease in 1-year all-cause mortality (simple model: hazard ratio, 0.36; P = 0.0015; complex model: hazard ratio, 0.35; P = 0.013). Veterans with ocular inflammation had significantly lower 1-year all-cause mortality than those without documented ocular inflammation. The reason for this finding remains to be established.


New Treatment for the Cognitive and Emotional Deficits Linked with Paclitaxel-Induced Peripheral Neuropathy in Mice.
Chemotherapy-provoked peripheral neuropathy and its linked comorbidities severely reduce the quality of a patient's life. Its therapy is not completely resolved and has become an important clinical challenge. The protective actions of molecular hydrogen (H2) in many neurological disorders have been described, but its effects on memory and the emotional deficits accompanying neuropathic pain induced by chemotherapy remain unknown. In this study, using male mice injected with paclitaxel (PTX), we examined the effects of systemic treatment with hydrogen-rich water (HRW) in: (i) the mechanical and thermal allodynia provoked by PTX and the pathways involved; (ii) the memory deficits, anxiety- and depressive-like behaviors associated with PTX-induced peripheral neuropathy (PIPN); and (iii) the plasticity (p-extracellular signal-regulated protein kinase; p-ERK ½), nociceptive (p-protein kinase B, p-Akt), inflammatory (p-nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; p-IKBα), and oxidative (4-hydroxynonenal: 4-HNE) alterations provoked by PIPN in the prefrontal cortex (PFC). The results revealed: (1) the antiallodynic actions of HRW administered at one or two times per day during 7 and 3 consecutive days; (2) the participation of Kv7 potassium channels and the Nrf2-heme oxygenase 1-NAD(P)H: quinone oxidoreductase 1 pathway in the painkiller effects of HRW; (3) the inhibition of memory deficits and the anxiodepressive-like behaviors related with PIPN induced by HRW; and (4) the normalization of p-ERK ½, p-Akt and 4-HNE up-regulation and the activation of antioxidant enzymes produced by this treatment in PFC. This study proposes HRW as a possible effective and safe therapy for PIPN and its associated cognitive and emotional deficits.


Hemiconvulsion-Hemiplegia-Epilepsy in a girl with cobalamin C deficiency.
Hemiconvulsion-Hemiplegia-Epilepsy initially involves an infantile presentation of febrile focal motor status epilepticus, with subsequent hemiplegia of the initially affected side. Months to years later, affected children go on to develop a chronic epilepsy with recurrent focal seizures which are often refractory to treatment. This uncommon paediatric epilepsy syndrome is poorly understood, with only a very small minority of cases associated with an underlying genetic or metabolic abnormality. We present a four-year-old girl with genetic cobalamin C deficiency who had a dramatic presentation with Hemiconvulsion-Hemiplegia-Epilepsy. She had febrile focal status epilepticus, with right hemiconvulsive seizures for nearly 10 hours, ultimately requiring a midazolam infusion. Over subsequent days, she developed progressively worsening cerebral oedema, leading to herniation and requiring a craniectomy to relieve pressure. This girl's presentation is the first association of cobalamin deficiency with hemiconvulsion-hemiplegia-epilepsy; and illustrates the importance of considering this entity when patients with this metabolic disorder present with acute deterioration. More importantly, the case also raises the possibility that derangements of cobalamin metabolism could be a contributing factor in cases of hemiconvulsion-hemiplegia-epilepsy, as well as febrile seizures in general.


Evidence for hyperplasia in mesenteric resistance vessels of spontaneously hypertensive rats using a three-dimensional disector.
Cellular dimensions in mesenteric resistance vessels from 10 spontaneously hypertensive rats and 10 Wistar-Kyoto rats have been determined using a random volume with an unbiased counting rule as the counting unit (the disector). With this method, vessels first were mounted on a myograph. Media thickness (spontaneously hypertensive rats, 11.3 micron; Wistar-Kyoto rats, 8.6 micron; P less than 0.01), lumen diameter (spontaneously hypertensive rats, 178 micron; Wistar-Kyoto rats, 194 micron; P greater than 0.1), and maximum active wall tension response (spontaneously hypertensive rats, 3.2 N/m; Wistar-Kyoto rats, 2.5 N/m; P less than 0.05) were determined. After fixation, serial sections normal to the long axis of the smooth muscle cells were made. In each vessel, the disector was a defined volume of the vessel wall (volume ca. 25 X 10(3) micron3) which was contained in about eight of these sections. The number of nuclei within the disector was counted using an unbiased, three-dimensional counting rule. On the basis that cells were mononuclear (an assumption that was tested), the ratio of this number divided by disector volume equaled the numerical cellular density. Measurement of the fraction of media taken up by smooth muscle cells then gave mean cell volume (spontaneously hypertensive rats, 563 micron3; Wistar-Kyoto rats, 615 micron3; P greater than 0.1). From the myograph measurements, the number of cells per unit length (spontaneously hypertensive rats, 10.4/micron; Wistar-Kyoto rats, 7.4/micron; P less than 0.05) and maximum force production per cell (spontaneously hypertensive rats, 5.1 microN; Wistar-Kyoto rats, 5.7 microN; P greater than 0.1) could then be calculated.(ABSTRACT TRUNCATED AT 250 WORDS)


Behavior of Mouse Spermatozoa in the Female Reproductive Tract from Soon after Mating to the Beginning of Fertilization.
Using transgenic mice with spermatozoa expressing enhanced green fluorescent protein in their acrosome and red fluorescent protein in their midpiece mitochondria, we followed the behavior of spermatozoa within the female genital tract after natural mating. When examined 15 min after coitus, many spermatozoa were around the opening of the uterotubal junction. Spermatozoa that entered the uterotubal junction were seemingly not moving, yet they steadily migrated toward the isthmus at a speed only time-lapse video recording could demonstrate. Many spermatozoa reaching the lower isthmus were motile. The site where spermatozoa attached and detached from the isthmus epithelium shifted from the lower to the upper segment of the isthmus with time. Virtually all the live spermatozoa within the lower isthmus were acrosome intact, whereas many of the actively motile spermatozoa in the upper isthmus were acrosome reacted. As far as we could observe, all the spermatozoa we found within the lumen of the ampulla and the cumulus oophorus were acrosome reacted. Even though we saw only a very few spermatozoa within the ampulla during fertilization, all were associated with, or were already within, oocytes, indicating that mouse fertilization in vivo is extremely efficient.


Non-puerperal vulval haematoma.
A case of non-puerperal vulval haematoma has been presented. The aetiology and surgical management plan of this uncommon condition has been discussed.


The prevalence and psychological costs of household violence by family members against women with disabilities in Cambodia.
Women with disabilities (WWDs) are at triple jeopardy due to the combined risks associated with gender, disability, and violence. Not only are WWDs marginalized socially but the violence against them in their own homes is largely neglected in domestic violence research. Evidence from developing countries is particularly sparse. A cross-sectional survey conducted in Cambodia found rates of violence by household members besides intimate partners were significantly higher among WWDs than non-disabled women. This violence engendered increased levels of psychological distress and higher rates of physical injury but low rates of disclosure to health workers and other formal sources of potential support. Community-based strategies are recommended to radically change social and cultural attitudes, beliefs, and responses to WWDs who are victims of household violence to reduce negative social reactions toward them and to make it safer for them to disclose and receive psychosocial, legal, and other necessary support for this underreported type of violence.


Surgical techniques and reattachment rates in retinal detachment due to macular hole.
We evaluated reattachment rates of the transvitreal and transscleral techniques for treating 250 eyes with retinal detachment due to macular hole. The initial success rate of the transvitreal approach was 56% (53/94). There was no difference between the results of gas tamponade alone and vitrectomy and gas tamponade. The initial success rate of the transscleral approach was 83% (130/156). Macular diathermy and macular buckling showed a higher reattachment rate than macular diathermy alone. The final success rates were the same (95%), regardless of which approach was selected as an initial technique. The patients whose initial transvitreal reattachment failed and who underwent additional transvitreal procedures (including macular laser photocoagulation) showed a success rate of 93%. We believe that gas tamponade, which has possibility of better visual prognosis, should be selected as an initial technique because the final success rate was found to be the same regardless of the initial surgical techniques.


E2-E3 ubiquitin enzyme pairing - partnership in provoking or mitigating cancers.
The ubiquitin-proteasome system (UPS) modulates carcinogenesis through ubiquitination of cancer-related target proteins, leading to their degradation in the proteasome. This may deactivate tumor suppressors or activate tumor promoters- either way causing homeostatic imbalance. As major components of the UPS, the E2 and E3 enzymes are recognized as pivotal determinants of substrate recognition and ubiquitination. Identification of E2-E3 pairing selectivity is particularly pertinent to early diagnosis and potential development of targeted cancer therapeutics. This review is motivated by recent findings and new insights into the molecular dynamics of ubiquitination triggered by specific E2-E3 pairing, leading to cancer initiation and progression if cancer suppressors are degraded or cancer suppression (if cancer promoters are degraded), respectively. We provide an overview of strategies employed in screening for E2-E3 interactions based on up-to-date studies focusing on the E2-E3 interface motifs. Of considerable recent interest is how E2 and E3 might switch their functional partnerships via UBE2O, which suggests an emerging significance on how UBE2O might influence E2-E3 pairing. Thus, a reflection on the role of UBE2O is included. Finally, we deliberate on the rational and cautious development of anti-cancer cocktail drugs which specifically target E2-E3 interacting residues for precision in cancer-killing with minimal side-effects. To this end, a list of potential future research is proposed.


Prevalence, genetic diversity and potential clinical impact of blood-borne and enteric protozoan parasites in native mammals from northern Australia.
A molecular survey was conducted to provide baseline information on the prevalence, genetic diversity and potential clinical impacts of blood-borne and enteric protozoans in native wild mammals from the Northern Territory (NT). A total of 209 blood and 167 faecal samples were collected from four target species; the northern brown bandicoot (Isoodon macrourus), common brushtail possum (Trichosurus vulpecula), northern quoll (Dasyurus hallucatus) and brush-tailed rabbit-rat (Conilurus penicillatus). Blood samples were screened by PCR at the 18S rRNA gene for trypanosomes, piroplasms and haemogregarines, with faecal samples tested for Cryptosporidium spp. at the 18S rRNA locus, and for Giardia spp. at the glutamate dehydrogenase (gdh) and 18S rRNA loci. The potential clinical impact was investigated by associating clinical, haematological and biochemical parameters with presence or absence of infection. Overall, 22.5% (95% CI: 17.0-28.8%) of the animals tested were positive for haemoprotozoans. Trypanosomes were found in 26.6% (95% CI: 18.7-35.7%) of the bandicoots and were identified as Trypanosoma vegrandis G6, except for one unique genotype, most similar to T. vegrandis G3 (genetic distance=7%). The prevalence of trypanosomes in possums was 23.7% (95% CI: 11.4-40.2%), and the genotypes identified clustered within the T. noyesi clade. The presence of Babesia sp. and Hepatozoon sp. was confirmed in bandicoots only, both at a prevalence of 9.7% (95% CI: 2.7-9.2%). The total prevalence of intestinal protozoan parasites observed was relatively low (3%; 95% CI: 1.0-6.9%). No evidence of clinical disease associated with protozoan parasitic infection was observed, however bandicoots positive for Trypanosoma exhibited a significantly lower packed cell volume (PCV) compared to negative bandicoots (p=0.046). To the authors' knowledge, this is the first research conducted in the NT to characterise protozoan parasites in threatened native mammals using both molecular and morphological tools; and to assess the potential clinical impacts of these agents. The absence of clear signs of major morbidity in infected animals seems to exclude a direct association between infections with these agents and possible population decline events in northern Australian native mammals. However until the cause(s) of population decline are ascertained for each individual mammal species, further studies are required. The outcome of the present investigation may be used to inform wildlife conservation and zoonotic disease programs.


Traumatic reactions as predictors of posttraumatic stress six months after the Oklahoma City bombing.
This study attempted to identify remembered reactions of Oklahoma City residents at the time of the April 1995 terrorist bombing that predicted later development of posttraumatic stress symptoms. Eighty-six adults who sought help for distress related to the bombing six months after it occurred completed a survey about demographic characteristics, level of exposure to the event, symptoms of grief, retrospective reports of reactions at the time of the trauma, current posttraumatic stress symptoms, and coping strategies. To identify immediate bombing reactions predictive of later distress, retrospective reports of reactions to the trauma were correlated with current posttraumatic stress symptoms. Multiple regression analysis was used to determine which reactions predicted the emergence of posttraumatic stress symptoms. Reactions of being nervous and being upset by how other people acted when the bombing occurred accounted for about one-third of the total variation in posttraumatic stress symptom scores and thus were major predictors of posttraumatic stress. These results differ from those of other studies in which peritraumatic dissociation, or dissociation at the time of the event, was more predictive than anxiety for developing later distress. The results suggest that persons who experience significant anxiety at the time of the traumatic event may continue to experience distress. Those who are overly concerned about others' actions may be showing diminished interpersonal trust, evidence of terrorism's ability to erode social harmony.


Gene polymorphisms of interleukin-10 and tumor necrosis factor-α are associated with contrast-induced nephropathy.
Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure. However, the pathogenesis of CIN remains unclear. This study evaluated the role of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) gene polymorphisms as CIN susceptibility markers after percutaneous coronary intervention (PCI). Four IL-10 tag SNPs (rs1554286, rs3021094, rs3790622, rs1800896) and three TNF-α tag SNPs (rs1799964, rs1800630, rs1800629) were analyzed by MALDI-TOF mass spectrometry in 53 CIN patients and 455 control subjects. Serum IL-10 and TNF-α were detected using ELISA. When compared to controls, the CIN patients showed increased frequencies of CC (rs1554286) and AG+GG (rs1800896) genotypes in IL-10 and GA+AA (rs1800629) genotype in TNF-α (OR = 2.24 (1.13-4.44), p = 0.018; OR = 2.61 (1.30-5.26), p = 0.005, and OR = 2.11 (1.08-4.09), p = 0.025, respectively). Baseline serum IL-10 levels in CIN patients were significantly lower (1.02 ± 1.14 vs. 2.78 ± 4.73 pg/ml, p = 0.008). Patients with CIN had a higher rate of decline in renal function than those without CIN (0.89 ± 1.67 vs. 0.30 ± 0.95 ml/min/1.73 m(2) per month, p = 0.002). Significantly higher rates of decline in creatinine clearance were noted in patients with TNF-α (rs1800629) GA+AA than GG genotype (0.88 ± 1.83 vs. 0.36 ± 0.70, p = 0.03), and with IL-10 (rs1800896) AG+GG than AA genotype (1.28 ± 2.14 vs. 0.33 ± 0.90, p < 0.001). Gene polymorphisms of IL-10 and TNF-α are associated with CIN risk and long-term renal outcome after PCI. More prospective studies are needed to confirm our results.


Plasma protein catabolism by the perfused rat liver. The effect of alteration of albumin concentration and dietary protein depletion.
1. The isolated perfused rat liver was used to study degradation rates of plasma albumin, transferrin and fibrinogen. 2. Constant fractional rates were observed for all three proteins even when the albumin concentration was drastically increased by the addition of large amounts to the perfusate pool. 3. Livers taken from rats deprived of dietary protein for 14-18 days showed greatly diminished fractional catabolic rates for albumin when perfused with blood from similarly deprived animals. 4. These rates could be restored to near-normal values by adding albumin or by perfusing with blood from normally fed rats. 5. These findings are consistent with the theory of pinocytosis as a step in the degradation of plasma proteins by hepatic parenchymal cells.


Increasing use of disease modifying drugs for MS in Canada.
The course of multiple sclerosis may be slowed by use of the disease modifying drugs (DMDs): subcutaneous or intramuscular interferon beta-1a, interferon beta-1b, glatiramer acetate, and natalizumab. We set out to compare utilization of these drugs in the Canadian provinces from 2002-2007. Using a retrospective cohort analysis, we reviewed population data from International Medical Statistics (IMS) Health between November 2001 and October 2007. The total annual number of DMD prescriptions increased from 3.9, in 2002, to 5.1, in 2007, per 1,000 Canadians. The total annual cost of prescriptions rose from $187 million to $287 million. Of the four provinces responsible for the majority of prescriptions--Alberta, BC, Ontario, and Quebec--Quebec had the highest average annual prescription rate (7 per 1,000 population) and BC had the lowest rate (3.3 per 1,000 population). Subcutaneous interferon beta-1a was the most commonly used drug whereas glatiramer acetate showed the greatest growth in use from 2002 to 2007. Disease modifying drugs prescription rates and costs increased by more than 30% between 2002 and 2007. There was wide variation in DMD prescription rates and relative drug preferences across the provinces.


Vasoconstrictor-induced protein-tyrosine phosphorylation in cultured vascular smooth muscle cells.
In cultured rat aortic smooth muscle cells, angiotensin II induced tyrosine phosphorylation of at least 9 proteins with molecular masses of 190, 117, 105, 82, 79, 77, 73, 45 and 40 kDa in time- and dose-dependent manners. Other vasoconstrictors such as [Arg]vasopressin, 5-hydroxytryptamine and norepinephrine induced the tyrosine phosphorylation of the same set of proteins as angiotensin II. The tyrosine phosphorylation of these proteins was mimicked by the protein kinase C-activating phorbol ester, phorbol 12 myristate 13-acetate, and the Ca2+ ionophore, ionomycin. These results demonstrate that the vasoconstrictors stimulate the tyrosine phosphorylation of several proteins in vascular smooth muscle cells and suggest that the tyrosine phosphorylation reactions are the events distal to the activation of protein kinase C and Ca2+ mobilization in the intracellular signalling pathways of the vasoconstrictors.


The effects of whole-body vibration on the cross-transfer of strength.
This study investigated whether the use of superimposed whole-body vibration (WBV) during cross-education strength training would optimise strength transfer compared to conventional cross-education strength training. Twenty-one healthy, dominant right leg volunteers (21 ± 3 years) were allocated to a strength training (ST, m = 3, f = 4), a strength training with WBV (ST + V, m = 3, f = 4), or a control group (no training, m = 3, f = 4). Training groups performed 9 sessions over 3 weeks, involving unilateral squats for the right leg, with or without WBV (35 Hz; 2.5 mm amplitude). All groups underwent dynamic single leg maximum strength testing (1RM) and single and paired pulse transcranial magnetic stimulation (TMS) prior to and following training. Strength increased in the trained limb for the ST (41%; ES = 1.14) and ST + V (55%; ES = 1.03) groups, which resulted in a 35% (ES = 0.99) strength transfer to the untrained left leg for the ST group and a 52% (ES = 0.97) strength transfer to the untrained leg for the ST + V group, when compared to the control group. No differences in strength transfer between training groups were observed (P = 0.15). For the untrained leg, no differences in the peak height of recruitment curves or SICI were observed between ST and ST + V groups (P = 1.00). Strength training with WBV does not appear to modulate the cross-transfer of strength to a greater magnitude when compared to conventional cross-education strength training.


Characterization of a human alpha1-antitrypsin variant that is as stable as ovalbumin.
The metastability of inhibitory serpins (serine proteinase inhibitors) is thought to play a key role in the facile conformational switch and the insertion of the reactive center loop into the central beta-sheet, A-sheet, during the formation of a stable complex between a serpin and its target proteinase. We have examined the folding and inhibitory activity of a very stable variant of human alpha1-antitrypsin, a prototype inhibitory serpin. A combination of seven stabilizing single amino acid substitutions of alpha1-antitrypsin, designated Multi-7, increased the midpoint of the unfolding transition to almost that of ovalbumin, a non-inhibitory but more stable serpin. Compared with the wild-type alpha1-antitrypsin, Multi-7 retarded the opening of A-sheet significantly, as revealed by the retarded unfolding and latency conversion of the native state. Surprisingly, Multi-7 alpha1-antitrypsin could form a stable complex with a target elastase with the same kinetic parameters and the stoichiometry of inhibition as the wild type, indicating that enhanced A-sheet closure conferred by Multi-7 does not affect the complex formation. It may be that the stability increase of Multi-7 alpha1-antitrypsin is not sufficient to influence the rate of loop insertion during the complex formation.


Reemerging Rice Orange Leaf Phytoplasma with Varying Symptoms Expressions and Its Transmission by a New Leafhopper Vector-Nephotettix virescens Distant.
Rice orange leaf phytoplasma (ROLP) belongs to the "Candidatus Phytoplasma asteris" 16SrI-B subgroup, which is solely transmitted by the zigzag-striped leafhopper (Recilia dorsalis Motchulsky) and the green leafhopper (Nephotettix cincticeps Uhler) (Hemiptera: Cicadellidae). Recently, rice plants showing orange leaf discoloration have become ubiquitous in several paddies of two provinces in the Philippines. In total of 98 symptomatic rice plants, 82% (Laguna) and 95% (Mindanao) were ROLP-positive by nested PCR detection. These plants showed more varying symptoms than previously reported. The vector insect R. dorsalis was scarcely present but green paddy leafhopper, N. virescens Distant (Hemiptera: Cicadellidae), was commonly observed in the paddies, thus the ability of N. virescens to transmit ROLP was thoroughly investigated. Newly emerged adult N. virescens, which fed on ROLD-source rice plants, were used to inoculate a susceptible rice seedling and was serially transferred into a new healthy seedling. Resultant positive transmission rates varied from 5.1% to 17.8%. The transmission ability of the insects was generally decreased over time. These findings suggest that N. virescens is an alternative vector of ROLP in the Philippines. Altogether, this study highlighted the increasing importance of ROLD-reemergence in Southeast and East Asia and proved the need for careful management of this alternative vector insect.


Versatile synthesis and micropatterning of nonfouling polymer brushes on the wafer scale.
In this article, the authors describe new approaches to synthesize and pattern surfaces with poly[oligo(ethylene glycol) methyl methacrylate] (POEGMA) polymer brushes synthesized by surface-initiated atom transfer radical polymerization. These patterned coatings confer "nonfouling" properties protein and cell resistance-to the surface in a biological milieu. The versatile routes for the synthesis of POEGMA demonstrated here offer clear advantages over other techniques previously used in terms of their simplicity, reliability, and ability to pattern large-area substrates. They also demonstrate that POEGMA polymer brushes can be patterned directly by photolithography, plasma ashing, and reactive ion etching to create patterns at the micro- and nanoscale over large areas with high throughput and repeatability, while preserving the protein and cell resistance of the POEGMA brush.


EFEMP2 Suppresses the Invasion of Lung Cancer Cells by Inhibiting Epithelial-Mesenchymal Transition (EMT) and Down-Regulating MMPs.
Epidermal growth factor-containing fibulin-like extracellular matrix protein 2 (EFEMP2), also known as fibulin-4, MBP1 and UPH1, is an extracellular matrix protein associated with a variety of tumors. The purpose of this study was to investigate the prognostic value and the function of EFEMP2 in lung cancer. The mRNA and protein expression of EFEMP2 in lung normal and cancer tissues, lung cancer cell lines (A549, H460, H1299 and H1650) and normal epithelial cell line BEAS-2B were evaluated by immunohistochemistry, RT-qPCR and Western blotting. The Public databases (Oncomine and Kaplan-Meier plotter) were used to investigate the prognostic value of EFEMP2 in lung cancer. RNA interference (RNAi) and overexpression transfection were performed to detect the effects of EFEMP2 up- or down-regulation on lung normal and cancer cell proliferation, invasion and metastasis in vitro and in vivo. EFEMP2 was lowly expressed in lung cancer tissues and cells, and its low expression was associated with malignant phenotype and poor prognosis of lung cancer. The same conclusion had been drawn from the Public databases. EFEMP2 overexpression significantly inhibited the invasion of lung cancer cells, hampered the process of EMT, and decreased the expression and activity of MMP2 and MMP9, while EFEMP2 knockdown remarkably enhanced the invasion of lung cancer cells, promoted EMT, and increased the expression and activity of MMP2 and MMP9. The low expression of EFEMP2 was detected in lung cancer and was positively correlated with the poor prognosis of patients. EFEMP2 was a tumor suppressor gene that inhibited the progress of lung cancer, which suggested a new research objective for the future studies.


Probing bistability in Fe(II) and Co(II) complexes with an unsymmetrically substituted quinonoid ligand.
The generation of molecular platforms, the properties of which can be influenced by a variety of external perturbations, is an important goal in the field of functional molecular materials. We present here the synthesis of a new quinonoid ligand platform containing an [O,O,O,N] donor set. The ligand is derived from a chloranilic acid core by using the [NR] (nitrogen atom with a substituent R) for [O] isoelectronic substitution. Mononuclear Fe(II) and Co(II) complexes have been synthesized with this new ligand. Results obtained from single crystal X-ray crystallography, NMR spectroscopy, (spectro)electrochemistry, SQUID magnetometry, multi-frequency EPR spectroscopy and FIR spectroscopy are used to elucidate the electronic and geometric structures of the complexes. Furthermore, we show here that the spin state of the Fe(II) complex can be influenced by temperature, pressure and light and the Co(II) complex displays redox-induced spin-state switching. Bistability is observed in the solid-state as well as in solution for the Fe(II) complex. The new ligand presented here, owing to the [NR] group present in it, will likely have more adaptability while investigating switching phenomena compared to its [O,O,O,O] analogues. Thus, such classes of ligands as well as the results obtained on the reversible changes in physical properties of the metal complexes are likely to contribute to the generation of multifunctional molecular materials.


Effectiveness and Safety of Rivaroxaban Versus Warfarin in Frail Patients with Venous Thromboembolism.
Frailty predicts poorer outcomes in patients receiving anticoagulation. We assessed the effectiveness and safety of rivaroxaban vs warfarin in frail patients experiencing venous thromboembolism. Using US MarketScan claims data from January 2012-December 2016, we identified frail patients (using the Johns Hopkins Claims-Based Frailty Indicator score) who had ≥1 primary hospitalization/emergency department visit diagnosis codes for venous thromboembolism, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30 days of the index event, and had ≥12 months of insurance prior to the index venous thromboembolism. Differences in baseline covariates between cohorts were adjusted using inverse probability of treatment weights based on propensity scores. The primary endpoint was the composite of recurrent venous thromboembolism or major bleeding. Patient claims were tracked for up to 12 months after the index venous thromboembolism or until endpoint occurrence oral anticoagulant discontinuation/switch, insurance disenrollment, or end of follow-up. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Of 58,089 incident venous thromboembolism patients identified, 6869 (1365 rivaroxaban and 5504 warfarin users) were classified as frail. Rivaroxaban reduced patients' hazard of the composite of recurrent venous thromboembolism or major bleeding (HR 0.75; 95% CI, 0.57-0.98) and recurrent venous thromboembolism alone (HR 0.65; 95% CI, 0.44-0.97) compared with warfarin. No significant difference in major bleeding was observed between cohorts (HR 0.88; 95% CI, 0.61-1.27). Frail patients experiencing a venous thromboembolism and given rivaroxaban experience less recurrent venous thromboembolism, with at least as good bleeding outcomes, as patients prescribed warfarin.


[Combined treatment of colon cancer with intensive preoperative irradiation].
The paper is concerned with the results of a randomized study of surgical and combined treatment of colon cancer patients using intensive preoperative irradiation; 102 were operated upon, 43 received combined treatment. It was shown that preoperative treatment did not raise the number of complications. Combined treatment made it possible to reduce the frequency of recurrences improving the 3-year survival rates.


Biochemical and functional characterization of anti-HIV antibody-ELP fusion proteins from transgenic plants.
The stability and recovery of recombinant proteins expressed in plants are improved by fusion to elastin-like peptides (ELPs). In order to test the suitability of ELP for the production of pharmaceutical proteins, transgenic plants were created that individually expressed the light and heavy chains of the broadly neutralizing anti-human immunodeficiency virus type 1 (anti-HIV-1) monoclonal antibody 2F5, which is being evaluated as a microbicide component. The antibody chains were expressed both with and without a C-terminal ELP fusion. Crossing these plants in all combinations resulted in transgenic lines producing the full antibody in four formats, with ELP on either the light or heavy chains, on both or on neither. Characterization of the affinity-purified antibodies by surface plasmon resonance spectroscopy showed that the kinetic binding parameters were identical to those of a Chinese hamster ovary (CHO) cell counterpart lacking ELP. N-Glycan analysis showed that all four derivatives contained predominantly oligo-mannose-type N-glycans and that the ELP fusions had no significant effect on N-glycan structure. It was concluded that ELP fusion to the light chain, heavy chain or both chains of a plant-derived antibody had no adverse affects on protein quality, but had a positive impact on the yield. ELP fusions do not interfere with folding, assembly, trafficking in the secretory pathway or post-translational modification, but enhance stability whilst at the same time simplifying recovery.


Comparison of the selection of antimicrobial resistance in fecal Escherichia coli during enrofloxacin administration with a local drug delivery system or with intramuscular injections in a swine model.
This study evaluated, for the first time, the selection of antibiotic resistance in fecal Escherichia coli, a potential reservoir of genes of resistance, during the prolonged exposure to fluoroquinolones after the implantation of a local drug delivery system (LDDS) in a swine model. Fourteen pigs were randomly assigned to group IM (5 mg/kg/day of intramuscular enrofloxacin--EFX) or LD (surgical implantation of EFX-polymethyl-methacrylate peri-femoral implants). Blood samples were collected daily for determination of plasma EFX and ciprofloxacin (CFX) concentrations. Fecal samples were collected daily to determine the E. coli counts and the susceptibility patterns of its isolates as evaluated by antibiotic disk diffusion tests. In both groups, EFX administration significantly reduced the bacterial counts after 2 days. During recolonization, the bacterial counts remained lower than baseline in group IM but not significantly, and almost reached pre-treatment levels in group LD. Susceptibility to EFX, CFX, and nalidixic acid of recolonizing E. coli in LD pigs slightly decreased but remained within the limit of "susceptible" isolates. In contrast, quinolone susceptibility of recolonizing E. coli in IM pigs dropped dramatically (P < 0.0001). In addition, intramuscular exposure to fluoroquinolones significantly decreased the susceptibility of E. coli to ampicillin and trimethoprim-sulfamethoxazole (P < 0.05). In conclusion, the use of a dosing regimen that minimized the intestinal output of fluoroquinolones also minimized the selection of resistance to several classes of antibiotics. This could represent another advantage of LDDS usage compared to long-lasting systemic administration of fluoroquinolones.


Impact of adjunctive cilostazol therapy on platelet function profiles in patients with and without diabetes mellitus on aspirin and clopidogrel therapy.
Cilostazol is a platelet inhibitor which when added to aspirin and clopidogrel has shown to reduce the risk of recurrent ischaemic events without an increase in bleeding. These clinical benefits have shown to be more pronounced in patients with diabetes mellitus (DM). However, it remains unknown whether cilostazol exerts different pharmacodynamic effects in patients with and without DM. This was a randomised, double-blind, placebo-controlled, cross-over pharmacodynamic study comparing platelet function in patients with and without DM on aspirin and clopidogrel therapy. Patients (n=111) were randomly assigned to either cilostazol 100 mg or placebo twice daily for 14 days and afterwards crossed-over treatment for another 14 days. Platelet function was performed at baseline, 14 days post-randomisation, and 14 days post-cross-over. Functional testing to assess P2Y12 signalling included flow cytometric analysis of phosphorylation status of vasodilator-stimulated phosphoprotein measured by P2Y12 reactivity index (PRI), light transmittance aggregometry and VerifyNow. Thrombin generation processes were also studied using thrombelastography. Significantly lower PRI values were observed following treatment with cilostazol compared with placebo both in DM and non-DM groups (p < 0.0001). The absolute between-treatment differences of PRI between groups was a 35.1% lower in patients with DM (p=0.039). Similar results were obtained using all other functional measures assessing P2Y12 signalling. Thrombin generation was not affected by cilostazol. Cilostazol reduces platelet reactivity both in patients with and without DM, although these pharmacodynamic effects are enhanced in patients with DM. Despite the marked platelet inhibition, cilostazol does not alter thrombin-mediated haemostatic processes, which may explain its ischaemic benefit without the increased risk of bleeding.


[Changes of the locomotor system in sportsmen with back pain].
Sport of high achievements is a complex combination of stressful factors affecting physical and psycological condition of a sportsman. Figure skating is a multicoordinational kind of sports. The analysis of the practical experience shows that movements undue in amplitude in the lumbar spinal column coupled with becoming too cold result in microtraumatization and origination of the pain syndrome in the loin. A 3-yr follow-up of 42 sportsmen-figureskaters of a top class athletic mastery was carried out to develop a system of prophylaxis and effective treatment of lumbar pains in sportsmen-figure skaters. The clinical neurological and orthopedic examination, X-ray, myotonometry of the paravertebral muscules, and USI of the spinal column were all done during the sports season and in the process of treatment. The developed system of a multiple-modality treatment showed efficacy of use of medicamentous (nonsteroidal antiinflammatory agents, chondroprotectors, antihomotoxic therapy, vitamins, and biological stimulants) and non-medicamentous (massage, stretching, physiotherapy, remedial gymnastics, psychological training) treatment options in rehabilitation of those sportsmen presenting with the pain syndrome in the lumbar spine.


A novel Bayesian geospatial method for estimating tuberculosis incidence reveals many missed TB cases in Ethiopia.
Reported tuberculosis (TB) incidence globally continues to be heavily influenced by expert opinion of case detection rates and ecological estimates of disease duration. Both approaches are recognised as having substantial variability and inaccuracy, leading to uncertainty in true TB incidence and other such derived statistics. We developed Bayesian binomial mixture geospatial models to estimate TB incidence and case detection rate (CDR) in Ethiopia. In these models the underlying true incidence was formulated as a partially observed Markovian process following a mixed Poisson distribution and the detected (observed) TB cases as a binomial distribution, conditional on CDR and true incidence. The models use notification data from multiple areas over several years and account for the existence of undetected TB cases and variability in true underlying incidence and CDR. Deviance information criteria (DIC) were used to select the best performing model. A geospatial model was the best fitting approach. This model estimated that TB incidence in Sheka Zone increased from 198 (95% Credible Interval (CrI) 187, 233) per 100,000 population in 2010 to 232 (95% CrI 212, 253) per 100,000 population in 2014. The model revealed a wide discrepancy between the estimated incidence rate and notification rate, with the estimated incidence ranging from 1.4 (in 2014) to 1.7 (in 2010) times the notification rate (CDR of 71% and 60% respectively). Population density and TB incidence in neighbouring locations (spatial lag) predicted the underlying TB incidence, while health facility availability predicted higher CDR. Our model estimated trends in underlying TB incidence while accounting for undetected cases and revealed significant discrepancies between incidence and notification rates in rural Ethiopia. This approach provides an alternative approach to estimating incidence, entirely independent of the methods involved in current estimates and is feasible to perform from routinely collected surveillance data.


[Risk of developing diabetes mellitus in primary care health users: a cross-sectional study].
to identify the risk of developing diabetes mellitus among primary care users in a municipality of the Southern Brazil. data were collected from October 2013 to April 2014 by applying the Finnish Diabetes Risk Score questionnaire on 189 users. the majority of the interviewees presented a slight moderate to moderate risk of developing diabetes mellitus (63.5%). There was a greater prevalence of high risk among the men. The variables with a significant prevalence ratio for high risk were age, obesity, abdominal circumference, sedentarism and family history of diabetes mellitus. the identified risk factors for diabetes reveal the importance of the health team and how it can intervene to prevent disease.


Genome Size Evolution within and between the Sexes.
Genome sizes are known to vary between closely related species, but the patterns behind this variation have yet to be fully understood. Although this variation has been evaluated between species and within sexes, unknown is the extent to which this variation is driven by differentiation in sex chromosomes. To address this longstanding question, we examine the mode and tempo of genome size evolution for a total of 87 species of Drosophilidae, estimating and updating male genome size values for 44 of these species. We compare the evolution of genome size within each sex to the evolution of the differences between the sexes. Utilizing comparative phylogenetic methods, we find that male and female genome size evolution is largely a neutral process, reflective of phylogenetic relatedness between species, which supports the newly proposed accordion model for genome size change. When similarly analyzed, the difference between the sexes due to heteromorphic sex chromosomes is a dynamic process; the male-female genome size difference increases with time with or without known neo-Y events or complete loss of the Y. Observed instances of rapid change match theoretical expectations and known neo-Y and Y loss events in individual species.


Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins.
Microtubules in yeast are essential components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. The relative importance in these processes of the two divergent alpha-tubulin genes of the budding yeast Saccharomyces cerevisiae, TUB1 and TUB3, was examined through the construction of null mutations and by increasing their copy number on chromosomes and on plasmids. Experiments with null alleles of TUB3 showed that TUB3 was not essential for mitosis, meiosis, or mating. Null alleles of TUB3, however, did cause several phenotypes, including hypersensitivity to the antimicrotubule drug benomyl and poor spore viability. On the other hand, the TUB1 gene was essential for growth of normal haploid cells. Even in diploids heterozygous for a TUB1 null allele, several dominant phenotypes were evident, including slow growth and poor sporulation. This functional difference between the two genes is apparently due to different levels of expression, because extra copies of either gene could suppress the defects caused by a null mutation in the other. We conclude that in spite of the 10% divergence between the products of the two genes, there is no essential qualitative functional difference between them.


Thalamocortical model for a propofol-induced alpha-rhythm associated with loss of consciousness.
Recent data reveal that the general anesthetic propofol gives rise to a frontal α-rhythm at dose levels sufficient to induce loss of consciousness. In this work, a computational model is developed that suggests the network mechanisms responsible for such a rhythm. It is shown that propofol can alter the dynamics in thalamocortical loops, leading to persistent and synchronous α-activity. The synchrony that forms in the cortex by virtue of the involvement of the thalamus may impede responsiveness to external stimuli, thus providing a correlate for the unconscious state.


The vitamin D pathway and mammographic breast density among postmenopausal women.
Laboratory studies have demonstrated that vitamin D has a number of chemopreventive properties, and that these properties may be mediated or modified by other molecules in the vitamin D pathway, such as parathyroid hormone (PTH) or calcium. However, there is little epidemiologic data exploring the effects of vitamin D on breast cancer risk in the context of these other molecules. We examined a panel of molecules in the vitamin D pathway in relation to mammographic breast density, a marker of breast cancer risk, in the Wisconsin Breast Density Study. A total of 238 postmenopausal women (ages 55-70, with no history of postmenopausal hormone use) were enrolled from mammography clinics in Madison, Wisconsin. Subjects provided blood samples that were analyzed for levels of 25-hydroxy vitamin D [25(OH)D], PTH, insulin-like growth factor-1 (IGF-1), IGF-binding protein 3 (IGFBP-3), retinol, and calcium. Percent breast density was measured using Cumulus software. In age-adjusted analyses there was a positive association between 25(OH)D and percent breast density (P = 0.05; mean percent density = 11.3% vs. 15.6% for 1st vs. 4th quartile of 25(OH)D). Breast density was inversely associated with PTH (P = 0.05; 16.0% vs. 11.4% for Q1 vs. Q4) and positively associated with the IGF-1:IGFBP-3 molar ratio (P = 0.02; 11.9% vs. 15.6% for Q1 vs. Q4). However, these associations were all null after further adjustment for body mass index (BMI; P > 0.25). The independent relation between 25(OH)D and breast density remained null among subgroups defined by BMI and serum levels of retinol, calcium, and estradiol. These results suggest no strong independent associations between the circulating molecules of the vitamin D pathway and mammographic breast density in postmenopausal women. While it remains possible that vitamin D could influence breast cancer risk, our results suggest that such an effect would be mediated through pathways other than breast density.


Effect of stenosed and occluded coronary arteries on immediate and late myocardial uptake of thallium-201.
Exercise and redistribution myocardial scintigraphy using thallium-201 was compared with the left ventricular angiogram and with the presence of stenosis or occlusion of coronary arteries on angiography. Irreversible scintigraphic defects representing areas of myocardial infarction were found in all patients with occlusion of the left anterior descending artery but nearly one-third of patients with stenosis of that artery also showed evidence of infarction. For the right coronary or circumflex arteries the incidence of infarction was 82% with vessel occlusion and 57% with vessel stenosis. Of abnormally contracting segments on the left ventricular angiogram, 95% showed irreversible scintigraphic defects but 33% of normally contracting segments supplied by a diseased artery also showed this. Myocardial infarction is not uncommon in patients with angina even in the absence of coronary occlusion. The incidence is underestimated by the left ventricular angiogram. These findings are of importance in the assessment of patients with coronary disease and their evaluation before coronary artery surgery.


Testosterone 5 alpha-reductase in spinal cord of Xenopus laevis.
Testosterone 5 alpha-reductase, the enzyme that converts testosterone to 5 alpha-dihydrotestosterone, is present in the spinal cord of Xenopus laevis. In adult males the enzymatic activity is optimal at pH 7.4 and 27 degrees C; the apparent Km is 2.0 x 10(-5) M and the Vmax is 10.0 pmol/mg protein/h. Enzymatic activity was assayed in segments of the spinal cord in each of four groups: control untreated males, females, castrated males, and sexually active clasping males. Striking differences in both the amount of dihydrotestosterone produced with time and in the pattern of its distribution were seen in spinal cords of clasping males compared with those of the other groups. The differences are greatest in the basal medulla and rostral segments of the spinal cord. Neurons in these segments innervate the muscles primarily involved in clasping.


PAX6 gene variations associated with aniridia in south India.
Mutations in the transcription factor gene PAX6 have been shown to be the cause of the aniridia phenotype. The purpose of this study was to analyze patients with aniridia to uncover PAX6 gene mutations in south Indian population. Total genomic DNA was isolated from peripheral blood of twenty-eight members of six clinically diagnosed aniridia families and 60 normal healthy controls. The coding exons of the human PAX6 gene were amplified by PCR and allele specific variations were detected by single strand conformation polymorphism (SSCP) followed by automated sequencing. The sequencing results revealed novel PAX6 mutations in three patients with sporadic aniridia: c.715ins5, [c.1201delA; c.1239A>G] and c.901delA. Two previously reported nonsense mutations were also found: c.482C>A, c.830G>A. A neutral polymorphism was detected (IVS9-12C>T) at the boundary of intron 9 and exon 10. The two nonsense mutations found in the coding region of human PAX6 gene are reported for the first time in the south Indian population. The genetic analysis confirms that haploinsuffiency of the PAX6 gene causes the classic aniridia phenotype. Most of the point mutations detected in our study results in stop codons. Here we add three novel PAX6 gene mutations in south Indian population to the existing spectrum of mutations, which is not a well-studied ethnic group. Our study supports the hypothesis that a mutation in the PAX6 gene correlates with expression of aniridia.


Fluorescent patterns of antibodies to mitochondria, endoplasmic reticulum and ribosomes.
The fluorescent patterns of autoantibodies to mitochondria, endoplasmic reticulum and ribosomes are described. Mitochondrial autoantibodies can be now divided in 10 types, microsomal antibodies at least in 3 types. Using rat renal tissue sections the typical fluorescent pattern of new antimitochondrial antibodies were: type 7, distal tubulus and third portion of proximal tubules, type 8 distal tubules, only, type 9 first and second portion of proximal tubules, type 10 strong reaction of distal and third portion of proximal tubules. The new pattern of ribosomal antibody is characterized by a cytoplasmic staining of rat hepatocytes especially in the central area of the liver lobule. The heterogeneity of cytoplasmic autoantibodies can be used as a diagnostic marker in different pathological conditions, if the different staining patterns is taken into account.


A water-soluble phosphorescent polymer for time-resolved assay and bioimaging of cysteine/homocysteine.
A water-soluble phosphorescent bioprobe was successfully developed by introducing an iridium(iii) complex as a phosphorescent signaling unit with poly(N-isopropylacrylamide) (PNIPAM) as the stimuli-responsive backbone. The probe was used for the effective detection of cysteine (Cys)/homocysteine (Hcy) and temperature based on changes in the phosphorescence signal. The design principle was based on the fact that the aldehyde groups in the cyclometalated ligands of the iridium(iii) complex moiety can react with the β- or γ-aminothiol group to form thiazolidine or thiazinane, respectively, resulting in a phosphorescence change in the iridium(iii) complex, thereby facilitating the detection of Cys and Hcy. Moreover, a phosphorescent hydrogel based on this probe was formed upon cross-linking and was then used as a quasi-solid sensing system for detecting Cys and Hcy. Furthermore, by using a time-resolved photoluminescence technique, the probe can detect Hcy in the presence of intense background fluorescence. In addition, phase changes in temperature-responsive PNIPAM can result in a switch of microenvironment between hydrophilicity and hydrophobicity, to which the phosphorescent emission of the iridium(iii) complex is very sensitive. This bioprobe integrates water solubility, biocompatibility, and sensing capability into one system, which is advantageous for biological applications. Further investigation of the application of the bioprobe for living-cell imaging confirmed that the probe is membrane permeable and is capable of detecting Cys in living cells with notable phosphorescence enhancement. Fluorescence lifetime imaging microscopy is successfully applied for sensing and bioimaging of intracellular Cys in the presence of short-lived background fluorescence.


A theoretical investigation of alpha-carbon kinetic isotope effects and their relationship to the transition-state structure of S(N)2 reactions.
[reaction: see text] The transition structures and alpha-carbon 12C/13C kinetic isotope effects for 22 S(N)2 reactions between methyl chloride and a wide variety of nucleophiles have been calculated using the B1LYP/aug-cc-pVDZ level of theory. Anionic, neutral, and radical anion nucleophiles were used to give a wide range of S(N)2 transition states so the relationship between the magnitude of the alpha-carbon kinetic isotope effect and transition-state structure could be determined. The results suggest that the alpha-carbon 12C/13C kinetic isotope effects for S(N)2 reactions will be large (near the experimental maximum) and that the curve relating the magnitude of the KIE to the percent transfer of the alpha-carbon from the nucleophile to the leaving group in the transition state has a broad maximum. This means very similar KIEs will be found for early, symmetric, and late transition states and that one cannot use the magnitude of these KIEs to estimate transition-state structure.


Suicidal behavior in the municipality of Baerum, Norway: a 12-year prospective study of parasuicide and suicide.
The present 12-year (1984-1995) surveillance study includes all hospitalized parasuicide patients (n = 1,031) as well as all suicides (n = 161) in the municipality of Baerum, a suburb of Oslo. The parasuicide rate decreased from 170 per 100,000 in 1984 to 79 per 100,000 in 1995 (53.5%). The parasuicide rates were lower than those in several comparable studies. Rates were higher for divorced females and separated males compared to married and other marital states, and the pattern of relative risk of parasuicide with respect to marital status was stable. Unemployment and substance abuse were positively correlated with parasuicidal behavior for both males and females. Approximately 33% reported one or more previous parasuicidal acts, and 21% repeated the parasuicide during the observation period. Ninety-four percent used self-poisoning as parasuicide method. A total of 2.4% of the parasuiciders committed suicide during the observation period. The mean annual suicide rate in Baerum was 19.0 per 100,000 compared to the national average of 14.7. The results support the notion of parasuicide and suicide being two different but overlapping populations. The implementation of a follow-up system for parasuiciders may have contributed to the reduced parasuicide rate during the study period.


Universal fluctuations in correlated systems
The probability density function (PDF) of a global measure in a large class of highly correlated systems has been suggested to be of the same functional form. Here, we identify the analytical form of the PDF of one such measure, the order parameter in the low temperature phase of the 2D XY model. We demonstrate that this function describes the fluctuations of global quantities in other correlated equilibrium and nonequilibrium systems. These include a coupled rotor model, Ising and percolation models, models of forest fires, sandpiles, avalanches, and granular media in a self-organized critical state. We discuss the relationship with both Gaussian and extremal statistics.


Wogonin inhibits multiple myeloma-stimulated angiogenesis via c-Myc/VHL/HIF-1α signaling axis.
Angiogenesis is associated with the progression of multiple myeloma (MM). Wogonin is an active mono-flavonoid with remarkable antitumor activity. However, its impact on MM-stimulated angiogenesis remains largely unknown. Here, we demonstrated that wogonin decreased expression and secretion of pro-angiogenic factors in MM cells via c-Myc/HIF-1α signaling axis, reducing MM-stimulated angiogenesis and MM cell proliferation in vivo. Overexpression of c-Myc in MM cells disrupted the balance between VHL SUMOylation and ubiquitination, and thus inhibited proteasome-mediated HIF-1α degradation. Impaired function of VHL ubiquitination complex in c-Myc-overexpressing cells was fully reversed by wogonin treatment via increasing HIF-1α-VHL interaction and promoting HIF-1α degradation. Collectively, our in vitro and in vivo studies reveal for the first time that wogonin represses MM-stimulated angiogenesis and tumor progression via c-Myc/VHL/HIF-1α signaling axis.


Pathophysiology of febrile nonhemolytic transfusion reactions.
Most febrile nonhemolytic transfusion reactions (FNHTR) to platelets are caused by cytokines that accumulate in the product during storage. There have been numerous studies that have demonstrated high concentrations of leukocyte- and platelet-derived cytokines in stored platelet products. The mechanism of cytokine accumulation is not understood; however, recent studies have suggested that leukocyte apoptosis and/or monocyte activation during the manufacturing process may play a role. Additional support of cytokines as a cause of FNHTR is provided by a recently published randomized controlled trial that shows that removal of the supernatant plasma from platelets before transfusion significantly lowers the frequency of reactions and eliminates most of the severe reactions associated with platelet transfusions. Although cytokines appear to play a major role in causing platelet reactions, there is little evidence to support their role in causing erythrocyte reactions. Hence, it appears that most febrile nonhemolytic transfusion reactions to erythrocytes are probably the result of an incompatibility between leukocytes in the erythrocyte product and antibodies in the recipient's plasma. Recent studies have confirmed that the concentrations of proinflammatory cytokines in a wide variety of stored erythrocyte products are low. Also, there is no clinical evidence to suggest that the small quantities of cytokines present in stored erythrocyte products contribute to acute reactions to these products when transfused.


[Gazing into the depths of the soul: hypnotism in documentary and instructional film (1920-1936)].
Although part of the medical fold since the 1870s, hypnosis was long relegated to the margins, recognised and used by only a relatively small group of medical professionals. In the decades around 1900 hypnotic techniques were monopolised as a form of medical treatment through a long and in no way linear process. Hypnosis of laymen was vehemently opposed, however, denounced as being far too dangerous. And yet, medical participation in the aura of spectacular intervention into the human psyche garnered support. The medium of both documentary and instructional film served an important function in this regard, conveying popular interest in acknowledging hypnosis as a scientific method. On the basis of four medically accredited films on hypnosis from 1920 to 1936, this paper attempts to investigate how medical experts and these genres, as part of their effort to claim hypnosis from the realm of public spectacle and parapsychological experimentation, worked to stabilise hypnosis as a purified form of medical and psychiatric practice.


Cumulative effect of COMT and 5-HTTLPR polymorphisms and their interaction with disease severity and comorbidities on the risk of psychosis in Alzheimer disease.
The objective of this study was to investigate the cumulative effect of the genes likely involved in Alzheimer disease (AD)-related psychosis and their interaction with disease stage and environmental factors. Two hundred thirty-four patients with AD underwent clinical and neuropsychologic examination, behavioral and psychiatric disturbances evaluation, and were subsequently divided into two subgroups according to the presence (AD-P) or the absence (AD-nP) of psychotic symptoms. Cathecol-O-methyltransferase (COMT), serotonin gene-linked promoter region (5-HTTLPR), and Apolipoprotein E (ApoE) genotypes were performed. COMT*H (H/H or H/liter; odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.13-5.11) and 5-HTTLPR*S (S/S or S/liter, OR: 2.14; 95% CI: 1.13-4.07) were associated with AD-P. A gene dose effect was observed; in fact, carriers of both polymorphisms showed a fivefold risk for psychosis compared with patients bearing no polymorphisms. An interaction between these two genetic variations with disease stage and ischemic cardiomyopathy was found, the latter influencing AD-P risk only if "at-risk" genetic polymorphisms were present. The combined trend effect of COMT*H plus 5-HTTLPR*S and advance disease stage on AD-P risk was approximately 200% greater than that predicted by assuming additive effects, whereas the one obtained by COMT*H plus 5-HTTLPR*S and ischemic cardiomyopathy was 50% greater. ApoE genotype did not influence AD-P risk. These findings claim for a synergic effect of COMT*H and 5-HTTLPR*S polymorphisms on the risk of psychosis in AD and for their interaction with disease stage and ischemic cardiomyopathy. This study suggests that considering both the genetic background and the environmental correlates might provide new insight for understanding psychosis mechanisms related to AD.


[Effectiveness of ultrasmall doses of endogenous bioregulators and immunoactive compounds].
The data and hypotheses on the mechanisms of action of ultrasmall doses (USD) and ultralow concentrations (ULC) of endogenous bioregulators and immunoactive compounds (regulatory peptides, cytokines, etc.) are presented. The reliability of the published data on the effectiveness of USD and ULC within the concentration limits 10(-13) - 10(-24) M and lower is considered.


Disturbance of methyl group metabolism in alloxan-diabetic sheep.
Alloxan-induced diabetes results in changes in the activities of a number of enzymes related to methyl group metabolism in sheep. Decreases in the activities of phospholipid methyltransferase and betaine-homocysteine methyltransferase in diabetic sheep liver indicate a reduced rate of choline synthesis and oxidation. A 65-fold increase in the activity of glycine methyltransferase and a 4-fold rise in the activity of gamma-cystathionase in diabetic sheep liver with elevated urinary excretion of cyst(e)ine suggest that catabolism of the methyl group of methionine and homocysteine was enhanced in the diabetic state.


Competing for space: female chimpanzees are more aggressive inside than outside their core areas.
Female space use can have important fitness consequences, which are likely due to differential access to food resources. Many studies have explored spatial competition in solitary species, but little is known about how individuals in social species compete over shared space. In this study, we investigate spatial patterns of aggression among female East African chimpanzees, Pan troglodytes schweinfurthii. This species provides an excellent opportunity to study spatial competition since (1) female chimpanzees occupy overlapping core areas (small areas of the community range in which individuals concentrate their space use) and (2) female core area quality is correlated with reproductive success, suggesting that females compete over long-term access to core areas. Here, we examine how female aggression towards other females varies inside and outside individual female core areas during a 14-year period at Gombe National Park, Tanzania. Overall, females showed higher rates of aggression inside than outside their own core areas. This pattern was driven by spatial variation in aggression in nonfeeding contexts. While food-related aggression did not vary spatially, females were more aggressive in nonfeeding contexts inside their core areas than they were outside their core areas. These results suggest that female chimpanzees follow a mixed strategy in which they compete for long-term access to resources in their core areas as well as for immediate access to food throughout the community range.


Structural effects on optoelectronic properties of halide perovskites.
Halide perovskites have prompted the evolution of the photovoltaic field and simultaneously demonstrated their great potential for application in other optoelectronic devices. A fundamental understanding of their structure-property relationship is essential to fabricate novel materials and high-performance devices. This review gives a perspective on different synthetic methodologies for the preparation of halide perovskites and highlights the effects of structural factors such as crystal structure, grain size, nanoscale dimensionality, patterned arrangement, and hierarchical structure on their optoelectronic properties. The main emphasis is given to 0D, 1D and 2D nanostructured materials including their common synthesis methods and key structural properties. Structural factors should be precisely controlled during the material preparation and device fabrication to improve the performance of targeted applications.


Pharmacokinetics, Immunogenicity, and Efficacy of Etanercept in Pediatric Patients With Moderate to Severe Plaque Psoriasis.
Etanercept has been recently approved in the United States for the treatment of moderate to severe plaque psoriasis in patients aged 4-17 years. The objective of this study was to characterize etanercept pharmacokinetics, immunogenicity, and efficacy in pediatric patients. Data from a phase 3 study and open-label extension study were analyzed. Etanercept serum concentrations in pediatric patients receiving etanercept 0.8 mg/kg (maximum, 50 mg) weekly were compared with adult psoriasis patients and pediatric patients with juvenile idiopathic arthritis (JIA) who received etanercept 0.4 mg/kg twice weekly. The developments of antietanercept antibodies and efficacy based on the Psoriasis Area and Severity Index were evaluated. Steady-state trough etanercept concentrations were similar across visits from weeks 12-48, between patients aged 4-11 and 12-17 years, between pediatric and adult psoriasis patients, and between pediatric patients with psoriasis or JIA. Etanercept serum concentrations and safety profiles were similar in patients with (15.9%) and without antietanercept antibodies. Dosing used in the study provided similar exposures and efficacy across ranges of weight and body mass index. Pharmacokinetic, immunogenicity, and efficacy data support 0.8 mg/kg (maximum, 50 mg) weekly dosing of etanercept in patients aged 4-17 years.


Dialyzable leukocyte extract differentially regulates the production of TNFalpha, IL-6, and IL-8 in bacterial component-activated leukocytes and endothelial cells.
To investigate i) whether the Dialyzable Leukocyte Extract (DLE) modulates the production of proinflammatory cytokines in leukocytes activated by the bacterial cell wall components lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN); ii) the effect of DLE on LPS-stimulated endothelial cells; and iii) whether the regulatory effect of DLE on inflammatory mediators is related to the modulation of Toll-like receptors (TLRs), NF-kappaB and cAMP signaling pathways. Leukocytes were stimulated with LPS, LTA, and PGN in the presence of DLE. Endothelial cells were stimulated with LPS and treated with DLE. The levels of Tumor Necrosis Factor-alpha(TNFalpha), Interleukin-6 (IL-6), and IL-8 in culture supernatants were evaluated by ELISA. The expression of Toll-like receptor 2 (TLR2) and 4 (TLR4), NF-kappaB activity and cAMP levels were evaluated by flow cytometry, EMSA, and EIA, respectively. The addition of DLE to leukocytes stimulated with cell wall constituents suppressed the production of TNFalpha. However, DLE induced IL-8 release in monocytes and enhanced IL-6 and IL-8 production by activated monocytes and endothelial cells. Also, DLE induced TLR2 and TLR4 expression, and increased cAMP levels, whereas NF-kappaB activity was inhibited. The present data indicate the differential regulation by DLE of the production of TNFalpha, IL-6, and IL-8 cytokines, associated with effects on TLR2 and TLR4 expression and NF-kappaB and cAMP activities. We suggest a putative mechanism for the biological effects of DLE in activated leukocytes and endothelial cells.


Severe pediatric head injury: the role of hyperemia revisited.
Diffuse cerebral swelling is a frequent finding after severe pediatric head injury, and is two to five times as common in children as in adults. Hyperemia or cerebrovascular engorgement has long been considered by many as the cause of diffuse swelling and raised intracranial pressure (ICP). Consequently, reduction of the vascular compartment by institution of hyperventilation and avoidance of mannitol has been advocated for the intensive care management of severely head-injured children. Suzuki and colleagues (1990) studied cerebral blood flow (CBF) in 80 normal, unanesthetized children. It was shown that CBF in normal children may range from 40 mL/100 g per minute during the first 6 months of life to a peak of 108 mL/100 g per minute at age 3 to 4 years, and down to 71 mL/100 g per minute after age 9 years. Considering this large range, comparisons of CBF data in children are valid only when small, well-defined age ranges are selected. When the CBF values of children with severe head injuries (described in previous research) were compared with normal values in children, there did not seem to be a substantial increase of CBF. Hyperemia may therefore not be as common in severe pediatric head injury as previously thought. Until we acquire a better understanding of the pathophysiology of severe pediatric head injury, and what the optimal treatment in children would be, there is no reason to treat children differently from adults.