Bone Marrow Adipokine Expression Was Associated With Decreased Erythroid Colony Growth After Trauma.
Proinflammatory and immunomodulatory adipokines are linked to inflammation in critically ill patients but are poorly studied after injury. We hypothesized that trauma would induce systemic adipokine release and influence erythroid suppression. Blood and bone marrow (BM) were collected from trauma patients (ISS > 15, n = 90) and compared to patients undergoing elective hip replacement (n = 37). Plasma adipokine levels were measured, and BM was assayed for adipokine transcription and erythroid progenitor growth potential. Differences were detected using t-tests and correlations using simple linear regression. Trauma patients exhibited decreased adiponectin (1.8* vs 3.4 mg/mL) and increased leptin (7.8* vs 4.6 ng/mL) and resistin (3.1* vs 2.5 ng/mL), with sex- and age-specific differences. They also showed increased BM visfatin transcription. Adipokine transcription negatively correlated with erythroid progenitor growth. Adipose tissue activity is linked to inflammatory responses after injury, with variability by age and sex. Bone marrow adipose tissue may influence erythroid recovery after trauma.


Doppler echocardiography in adults with isolated ventricular septal defect.
Doppler echocardiography and cardiac catheterization were undertaken in 70 consecutive patients, 31-68 years of age (mean 39), who had isolated congenital ventricular septal defects (VSD), 28 of whom had been operated upon. In 50 patients with invasively proven VSD, 37 had a correct Doppler diagnosis of VSD (group 1) and in 13 a false negative result was obtained (group 2); i.e. a sensitivity of 74%. No false positive Doppler diagnosis was made in the 20 patients without evidence of shunt. Left to right ventricular systolic pressure difference (delta P) ranged between 55 and 142 mm Hg, with a mean value of 103 mm Hg in group 1 and 99 mm Hg in group 2. There was good correlation between delta P obtained by continuous wave Doppler and catheterisation in 17 group 1 patients with moderate and large shunts (r = 0.81, P less than 0.001). There was no correlation in the remaining 20 patients in group 1 with small shunts (r = 0.20, P greater than 0.1). Doppler echocardiography in the adult with isolated VSD has good sensitivity and excellent specificity. Doppler prediction of delta P is reasonably correct in patients with moderate and large shunts, but of no value in patients with small shunts.


Morphoproteomics and Etiopathogenic Features of Pulmonary COVID-19 with Therapeutic Implications: A Case Study.
The COVID-19 pandemic has challenged the world economically and medically. Understanding and defining the biology of this specific coronavirus infection may lead to targeted therapies to lessen its virulence and expand the host resistance. This study's objective was to apply morphoproteomics to pulmonary lung sections from a forensic autopsy of an untreated COVID-19 victim, so that we may better define its biology from the perspective of its interaction with the host and provide options for therapeutic targets. Morphoproteomic analysis from a case study of this COVID-19 pulmonary infection included immunohistochemical probes to detect phosphorylated p-STAT3 (Tyr 705), as part of the interleukin (IL)-6 pathway; cyclooxygenase (COX)-2, CD8+ cytotoxic lymphocytes, Programmed Death (PD)-1 receptor+ lymphoid cells, CD56+ NK lymphoid cells, CD163+ (M2 polarized monocytes/macrophages), and programmed death-ligand 1 (PD-L1) expression as part of the host response to interaction with the COVID-19 virus. Representative sections of the COVID-19 victim's lung showed: nuclear expression of p-STAT3 (Tyr 705) in many of the alveolar pneumocytes and in occasional endothelial cells; COX-2 expression in the alveolar pneumocytes; a relative paucity of CD8+ cytotoxic lymphocytes; absence of CD56+ NK lymphoid cells; abundance of intra-alveolar and alveolar interstitial CD163+ macrophages/monocytes; PD-L1 expression on occasional macrophages, focally on collections of alveolar pneumocytes, and on cells in the alveolar interstitium; and rare PD-1+ lymphocytes in similar regions as CD8+ lymphocytes. Morphoproteomics and microanatomical features coincide with the etiopathogenic features of pulmonary coronavirus infection and the host response. This suggests that a targeted therapy could address the biology of COVID-19 pneumonia, enhance the host immune response and prevent its progression to a life-threatening, ventilator-dependent clinical situation.


Using off-target data from whole-exome sequencing to improve genotyping accuracy, association analysis and polygenic risk prediction.
Whole-exome sequencing (WES) has been widely used to study the role of protein-coding variants in genetic diseases. Non-coding regions, typically covered by sparse off-target data, are often discarded by conventional WES analyses. Here, we develop a genotype calling pipeline named WEScall to analyse both target and off-target data. We leverage linkage disequilibrium shared within study samples and from an external reference panel to improve genotyping accuracy. In an application to WES of 2527 Chinese and Malays, WEScall can reduce the genotype discordance rate from 0.26% (SE= 6.4 × 10-6) to 0.08% (SE = 3.6 × 10-6) across 1.1 million single nucleotide polymorphisms (SNPs) in the deeply sequenced target regions. Furthermore, we obtain genotypes at 0.70% (SE = 3.0 × 10-6) discordance rate across 5.2 million off-target SNPs, which had ~1.2× mean sequencing depth. Using this dataset, we perform genome-wide association studies of 10 metabolic traits. Despite of our small sample size, we identify 10 loci at genome-wide significance (P < 5 × 10-8), including eight well-established loci. The two novel loci, both associated with glycated haemoglobin levels, are GPATCH8-SLC4A1 (rs369762319, P = 2.56 × 10-12) and ROR2 (rs1201042, P = 3.24 × 10-8). Finally, using summary statistics from UK Biobank and Biobank Japan, we show that polygenic risk prediction can be significantly improved for six out of nine traits by incorporating off-target data (P < 0.01). These results demonstrate WEScall as a useful tool to facilitate WES studies with decent amounts of off-target data.


Site-specific performance of 68Ga-DOTATATE PET/CT in detecting tumors with ectopic adrenocorticotropic hormone secretion.
The aim of this study was to assess the detection ability of 68Ga-DOTATATE in pulmonary versus extrapulmonary tumors with ectopic adrenocorticotropic hormone secretion (EAS). Images of 68Ga-DOTATATE PET/CT from 74 patients with suspected EAS were retrospectively reviewed. EAS tumors were confirmed in 39 patients through surgical resection or biopsy. Image findings were compared with the histopathological results. EAS tumors were pathologically confirmed via surgery or biopsy in 39 patients. Among those 39 patients, 25 were with pulmonary neuroendocrine tumors (NETs), and the remaining 14 were with extrapulmonary NETs. 68Ga-DOTATATE PET/CT correctly identified the tumor in 26 patients, rendering an overall detection rate of 66.7%. On a site-based analysis, 68Ga-DOTATATE PET/CT correctly identified the EAS tumor in 13 of 25 patients with pulmonary NETs, yielding a detection rate of 52%; for the 14 patients with extrapulmonary NETs, 68Ga-DOTATATE PET/CT correctly identified the EAS tumor in 13, yielding a detection rate of 92.9%. The detection rate of 68Ga-DOTATATE was significantly higher in extrapulmonary NETs than in pulmonary NETs (92.9%% vs. 52%, P = 0.013). For the 13 patients with positive pulmonary NETs, the tumor SUVmax ranged from 1.1 to 7.4 with an average SUVmax of 3.1 ± 2.1. For the 13 patients with positive extrapulmonary NETs, the tumor SUVmax ranged from 2.7 to 21.8 with an average SUVmax of 9.9 ± 6.3. The tumor SUVmax was significantly higher in extrapulmonary tumors than pulmonary tumors (P = 0.015). The tumor size was smaller in pulmonary tumors than in extrapulmonary tumors, while the difference was not significant (P = 0.516). 68Ga-DOTATATE showed site-specific difference in detecting tumors with EAS secretion. Specifically, 68Ga-DOTATATE performed better in the extrapulmonary EAS tumors than in pulmonary ones with both higher detection rate and uptake. Combination of anatomic imaging techniques are necessary for the correct diagnosis of pulmonary EAS tumors.


Monitoring attentional style and medical regimen adherence in hemodialysis patients.
Previous research involving individuals facing chronic health problems suggests that an attentional style characterized by pronounced monitoring of threat-relevant information is associated with poorer behavioral and emotional adjustment. This study examined the hypothesis that a pronounced monitoring style would be associated with poorer medical regimen adherence in a sample of 51 chronic hemodialysis patients. Hierarchical regression analyses (controlling for demographic factors and trait anxiety) revealed that "high monitors" exhibited higher interdialysis weight gains and higher serum K values reflecting poorer adherence to fluid-intake and dietary restrictions. However, monitoring was not associated with a measure of medication adherence. Partial support was found for a model suggesting that a lack of perceived control is responsible for the relationship between higher monitoring and poorer adherence.


Singlet oxygen generation using iodinated squaraine and squaraine-rotaxane dyes.
The goal of this study was to assess the ability of squaraine-rotaxanes to generate singlet oxygen for potential application in photodynamic therapy (PDT). Specifically, we compare the aggregation and photophysical properties of an iodinated squaraine dye and an iodinated squaraine-rotaxane. Even under strongly aggregating conditions, the absorption spectra of both remain relatively sharp. An X-ray crystal structure of the iodinated squaraine dye shows that it adopts perpendicular, end-to-face orientations in the solid state. Singlet oxygen generation efficiency was measured by trapping with 1,3-diphenylisobenzofuran. The triplet state of the rotaxane was characterized using laser flash photolysis. The results of this study suggest that heavily halogenated squaraine-rotaxanes have potential as singlet oxygen photosensitizers for PDT.


Vitamin A supplementation ameliorates butyric acid-induced intestinal mucosal injury in newborn rats.
Vitamin A (vit A) plays an important role in wound healing and therefore may help in repairing of intestinal mucosal injury. The purpose of this study was to determine if vit A supplementation could promote healing in intestinal mucosal injury as commonly seen in neonatal necrotizing enterocolitis (NEC). Mild intestinal mucosal injury was induced in 10-day-old Sprague-Dawley rats by luminal administration of 1.5% butyric acid (BA) at pH 4.0. Normal saline at the same pH was administered as control. Immediately after administrations of BA or normal saline, animals were randomly assigned to receive high dose vit A (20,000 IU/kg for one dose, i.p.), low dose vit A (5,000 IU/kg for two doses) or vehicle. Animals were followed for 48 hours and then sacrificed for histological examination. Rats with BA-induced intestinal mucosal injury had a reduction in daily weight gain (p < 0.05). Vit A supplementation significantly improved the daily weight gain in the rats with BA-induced intestinal mucosal injury and the effect is dose dependent. At sacrifice, the colon wet weight was significantly heavier and the histological injury scores from both ileum and proximal colon higher in the rats with BA-induced intestinal mucosal injury. All of those parameters were improved with vit A supplementation. We conclude that vit A supplementation ameliorates BA induced-intestinal mucosal injury in newborn rats.


Evaluation of Fibular Fracture Type vs Location of Tibial Fixation of Pilon Fractures.
Comminuted fibular fractures can occur with pilon fractures as a result of valgus stress. Transverse fibular fractures can occur with varus deformation. No definitive guide for determining the proper location of tibial fixation exists. The purpose of this study was to identify optimal plate location for fixation of pilon fractures based on the orientation of the fibular fracture. One hundred two patients with 103 pilon fractures were identified who were definitively treated at our institution from 2004 to 2013. Pilon fractures were classified using the AO/OTA classification and included 43-A through 43-C fractures. Inclusion criteria were age of at least 18 years, associated fibular fracture, and definitive tibial plating. Patients were grouped based on the fibular component fracture type (comminuted vs transverse), and the location of plate fixation (medial vs lateral) was noted. Radiographic outcomes were assessed for mechanical failures. Forty fractures were a result of varus force as evidenced by transverse fracture of the fibula and 63 were due to valgus force with a comminuted fibula. For the transverse fibula group, 14.3% mechanical complications were noted for medially placed plate vs 80% for lateral plating ( P = .006). For the comminuted fibular group, 36.4% of medially placed plates demonstrated mechanical complications vs 16.7% for laterally based plates ( P = .156). Time to weight bearing as tolerated was also noted to be significant between groups plated medially and laterally for the comminuted group ( P = .013). Correctly assessing the fibular component for pilon fractures provides valuable information regarding deforming forces. To limit mechanical complications, tibial plates should be applied in such a way as to resist the original deforming forces. Level of Evidence Level III, comparative study.


The Schirmer tear test in rhesus monkeys (Macaca mulatta).
A clinical case of keratoconjunctivitis sicca prompted a study to determine normal values for the Schirmer tear test in rhesus monkeys. Normal values for rhesus monkeys were calculated to be 6 to 24 mm wetting/minute (mean = 15.1) and it was determined that neither sex nor ketamine had a statistically significant effect on these values.


Dermal electrosurgical shave excision.
The dermal electrosurgical shave excision is a fast and inexpensive method of removing epidermal and dermal lesions. The procedure is ideally suited for pedunculated lesions raised above the level of the surrounding skin. It consists of repetitive, unidirectional, horizontal slicing of a cutaneous lesion with a no. 15 blade followed by electrosurgical feathering to smooth out the wound edges. A smoke evacuator is used during electrosurgery to prevent inhalation of heat-disseminated viral particles. The procedure is followed by histologic evaluation of the shaved specimen. Suspicious pigmented lesions should not be shaved because the long-term prognosis of a malignancy may depend on the thickness of the lesion on histologic analysis. Administration of adequate local anesthesia should make this a painless procedure. Basic general surgery skills are required, and formal training in electrosurgery is highly recommended.


Cerebellar Cathodal Transcranial Direct Stimulation and Performance on a Verb Generation Task: A Replication Study.
The role of the cerebellum in cognitive processing is increasingly recognized but still poorly understood. A recent study in this field applied cerebellar Transcranial Direct Current Stimulation (c-tDCS) to the right cerebellum to investigate the role of prefrontal-cerebellar loops in language aspects of cognition. Results showed that the improvement in participants' verbal response times on a verb generation task was facilitated immediately after cathodal c-tDCS, compared to anodal or sham c-tDCS. The primary aim of the present study is to replicate these findings and additionally to investigate possible longer term effects. A crossover within-subject design was used, comparing cathodal and sham c-tDCS. The experiment consisted of two visits with an interval of one week. Our results show no direct contribution of cathodal c-tDCS over the cerebellum to language task performance. However, one week later, the group receiving cathodal c-tDCS in the first visit show less improvement and increased variability in their verbal response times during the second visit, compared to the group receiving sham c-tDCS in the first visit. These findings suggest a potential negative effect of c-tDCS and warrant further investigation into long term effects of c-tDCS before undertaking clinical studies with poststroke patients with aphasia.


Roles of different subtypes of opioid receptors in mediating the ventrolateral orbital cortex opioid-induced inhibition of mirror-neuropathic pain in the rat.
Previous studies have demonstrated that opioid receptors in the prefrontal ventrolateral orbital cortex (VLO) are involved in anti-nociception. The aim of this current study was to examine whether opioid receptors in the VLO have effects on the hypersensitivity induced by contralateral L5 and L6 spinal nerve ligation (SNL), termed as mirror neuropathic pain (MNP) in the male rat. Morphine (1.0, 2.5, 5.0 microg) microinjected into the VLO contralateral to the SNL depressed the mechanical paw withdrawal assessed by von Frey filaments and the cold plate (4 degrees C)-induced paw lifting in a dose-dependent manner on the side without SNL. These effects were antagonized by microinjection of the non-selective opioid receptor antagonist naloxone (1.0 mug) into the same VLO site. Microinjection of endomorphin-1 (5.0 microg), a highly selective mu-opioid receptor agonist, and [d-Ala(2), d-Leu(5)]-enkephalin (DADLE, 10 microg), a delta-/mu-receptor agonist, also depressed the MNP. The effects of both drugs were blocked by selective mu-receptor antagonist beta-funaltrexamine (beta-FNA, 3.75 microg), but the effect of the DADLE was not influenced by the selective delta-receptor antagonist naltrindole (5.0 microg). Microinjection of the kappa-opioid receptor agonist spiradoline mesylate salt (U-62066) (100 microg) had no effect on the MNP. These results suggest that the VLO is involved in opioid-induced inhibition of the MNP and the effect is mediated by mu- (but not delta- and kappa-) opioid receptors.


External Compression of Epicardial Coronary Arteries with Partial Calcific Pericarditis.
Calcific pericarditis (CP) is a rare disease which results from long-standing pericardial inflammation. Pericardial calcification may completely or partially encase the ventricles, resulting in impaired diastolic filling. We present a case of a 53-year-old male who was incidentally found to have annular CP resulting in external compression of a large territory diagonal branch (D1) reaching the apex with likely chronically occluded left anterior descending artery with collateral circulation from the right coronary artery with hemodynamic compromise on coronary angiography. This was emergently treated with a drug-eluting stent with improved D1 flow and entailed the importance of percutaneous coronary intervention as a viable option in cases of CP resulting in acute hemodynamic compromise.


Histological analysis of retraction pocket pars tensa of tympanic membrane in children.
Histological and histochemical analysis of retraction pocket of pars tensa of tympanic membrane in children. Identification of morphological abnormalities in comparison with a healthy tympanic membrane as it is described in standard textbook. Identification of signs typical for cholesteatoma and support for a retraction theory of cholesteatoma formation. A prospective study analysing 31 samples of retraction pockets taken during surgery. University Hospital, Children's Medical Centre Samples of retraction pockets were processed by a standard process for light microscopy, stained by haematoxylin-eosin. Van Gieson's stain was used for differential staining of collagen, Verhoeff's stain for elastic fibre tissues, Alcian blue for acidic polysaccharides and PAS (Periodic Acid Schiff) method for basement membrane polysaccharides. The following findings were observed in the samples of retraction pockets: hyperkeratosis (100%), hypervascularisations (100%), subepithelial fragmented elastic fibres (96%), myxoid changes (87%), subepithelial inflammatory infiltration (84%), rete pegs (71%), papilomatosis (71%), intraepithelial inflammatory cellularizations, (48%), intraepithelial spongiosis (16%) and parakeratosis (3%). No basement membrane continuity interruptions were observed. Thickness of retraction pocket, thickness of epidermis, occurrence of rete pegs and frequency of fragmented elastic fibres was higher in a Grade III stage RP than Grade II stage RP (according to Charachon). Morphological abnormalities in the structure of retraction pockets in comparison with a healthy tympanic membrane were described. The changes are typical for a structure of cholesteatoma (these changes are common in matrix and perimatrix), supporting retraction theory of its origin. Our observations show that it is inflammation that probably plays a key role in the pathogenesis of retraction pocket. The frequency of some of the changes increases with the stage of retraction pocket (II-III according to Charachon). Basement membrane continuity interruptions are not typical for retraction pockets.


Socioeconomic differences in smoking in Jordan, Lebanon, Syria, and Palestine: A cross-sectional analysis of national surveys.
The association between education and wealth, as fundamental determinants of health, and smoking is well-established. Yet, social inequalities have received little attention in the expanding field of tobacco research in the Arab region. In this study, we examine inequalities in cigarette smoking by education and wealth in four Arab countries. Utilizing the most recently available population-level data sets (Syria 2009 PAPFAM, Jordan 2012 DHS, Palestine 2010 Family Health Survey, and Lebanon 2004 PAPFAM), we tested the association between cigarette smoking and education and wealth-controlling for age, marital status, and region of residence-for each country, and among men and women depending on data availability. Cigarette smoking prevalence among Arab men is high- 51.3% in Syria, 39.7% in Palestine, and 42.1% in Lebanon; among women, prevalence is 8.4% in Syria, 10.9% in Jordan, and 24.3% Lebanon. Cigarette smoking shows the expected patterns inequalities by education among men in Syria, Palestine, and Lebanon, and among women in Jordan and Lebanon. On the other hand, wealth does not show a clear pattern in its association with cigarette smoking and, in some cases (men in Palestine and women in Syria) the behavioral risk is higher among the wealthiest. Available data from 2004-2012 show that cigarette smoking among men and women in the four Arab countries is predominant among those with limited access to education as a fundamental cause. The weak or absent negative association between wealth and cigarette smoking suggests that access to material resources does not precipitate a reduction in the consumption of tobacco.


Calorimetry-Derived Composition Vectors to Resolve Component Raman Spectra in Phospholipid Phase Transitions.
Multidimensional least squares analysis is a well-established technique for resolving component vibrational spectra from mixed samples or systems. Component resolution of temperature-dependent vibrational spectra is challenging, however, due to the lack of a suitable model for the variation in sample composition with temperature. In this work, analysis of temperature-dependent Raman spectra of lipid membranes is accomplished by using "concentration" vectors independently derived from enthalpy changes determined by differential scanning calorimetry. Specifically, the lipid-bilayer phase transitions of DMPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) are investigated through Raman spectra acquired from individual, optically trapped vesicles in suspension as a function of temperature. Heat capacity profiles of the same vesicle suspension are measured using differential scanning calorimetry and numerically integrated to generate enthalpy change curves of each phase transition, which are in turn used to construct composition vectors. Multidimensional least squares analysis optimized for a fit to these composition vectors allows resolution of the component spectra corresponding to gel, ripple, and liquid-crystalline phases of the DMPC. The quality of fit of the calorimetry-derived results is confirmed by unstructured residual differences between the data and the model, and a composition variation predicted by the resolved spectra that matches the calorimetry results. This approach to analysis of temperature-dependent spectral data could be readily applied in other areas of materials characterization, where one is seeking to learn about structural changes that occur through temperature-dependent phase transitions.


Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas from 1995 to 2013.
Although rare, primary central nervous system (CNS) tumors are associated with significant morbidity and mortality. Texas is a representative sample of the United States population given its large population, ethnic disparities, geographic variations, and socio-economic differences. This study used Texas data to determine if variations in incidence trends and rates exist among different ethnicities in Texas. Data from the Texas Cancer Registry from 1995 to 2013 were examined. Joinpoint Regression Program software was used to obtain the incidence trends and SEER*Stat software was used to produce average annual age-adjusted incidence rates for both nonmalignant and malignant tumors in Texas from 2009 to 2013. The incidence trend of malignant primary CNS tumors in whites was stable from 1995 to 2002, after which the annual percent change decreased by 0.99% through 2013 (95% CI, -1.4, -0.5; P = .04). Blacks and Asian/Pacific Islanders showed unchanged incidence trends from 1995 to 2013. Hispanics had an annual percent change of -0.83 (95% CI, -1.4, -0.2; P = .009) per year from 1995 through 2013. From 2009 to 2013, the incidence rates of nonmalignant and malignant primary CNS tumors were highest among blacks, followed by whites, Hispanics, Asians, and American Indians/Alaskan Natives. Consistent with the 2016 Central Brain Tumor Registry of the United States report, the black population in Texas showed the highest total incidence of CNS tumors of any other race studied. Many factors have been proposed to account for the observed differences in incidence rate including geography, socioeconomic factors, and poverty factors, although the evidence for these external factors is lacking.


Gold Nanoparticles Compromise TNF-α-Induced Endothelial Cell Adhesion Molecule Expression Through NF-κB and Protein Degradation Pathways and Reduce Neointima Formation in A Rat Carotid Balloon Injury Model.
The aim of this study was to investigate the anti-inflammatory effects and mechanism of action of the gold nanoparticles (AuNPs) on vascular injury. In vitro vascular endothelial cell (EC) inflammation and in vivo rat carotid balloon injury models were used. The expression of TNF-α-induced cell adhesion molecules (CAMs) was suppressed by the AuNPs in human umbilical vein ECs and aortic ECs. The AuNPs reduced TNF-α-induced intracellular ROS production and NF-κB signaling pathways and enhanced CAM protein degradation by increasing their ubiquitination. However, they did not interfere with the mTOR pathway for protein synthesis and TNF-αbinding to ECs. These effects led to a reduction of monocyte adhesion to EC monolayers in vitro and endothelial CAM expression and monocyte/macrophage level in the vascular injured areas, contributing to a substantial decrease of arterial neointima formation in the rat carotid balloon injury model. The serum gold concentration was 99.5±18 ng/ml after three-day oral administration. Moreover, incubation of the AuNPs with serum and albumin led to an increase of particle sizes of the AuNPs. Collectively, we provide the first evidence that demonstrates that AuNPs possess anti-inflammatory bioactivity on vascular ECsin vitro and can reduce arterial neointima hyperplasia during vascular injury in vivo.


Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation.
Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell's own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response. Once processed, the peptide repertoire presented by MHC proteins largely depends on structural features of the binding groove of each particular MHC allelic variant. Additionally, two peptide editors-tapasin for class I and HLA-DM for class II-contribute to the shaping of the presented peptidome by favoring the binding of high-affinity antigens. Although there is a vast amount of biochemical and structural information, the mechanism of the catalyzed peptide exchange for MHC class I and class II proteins still remains controversial, and it is not well understood why certain MHC allelic variants are more susceptible to peptide editing than others. Recent studies predict a high impact of protein intermediate states on MHC allele-specific peptide presentation, which implies a profound influence of MHC dynamics on the phenomenon of immunodominance and the development of autoimmune diseases. Here, we review the recent literature that describe MHC class I and II dynamics from a theoretical and experimental point of view and we highlight the similarities between MHC class I and class II dynamics despite the distinct functions they fulfill in adaptive immunity.


Communicating hydrocephalus secondary to superior vena caval obstruction. Occurrence after Mustard's operation for transposition of the great arteries.
Communicating hydrocephalus was observed on computed tomographic (CT) scans in two infants who had previously undergone Mustard's operation for transposition of the great arteries. Obstruction of the superior limb of the intracardiac baffle developed in these children, resulting in venous obstruction to the head and upper extremities that resulted in cranial enlargement. Radiologic clues included a bulging superior vena cava and a prominent azygous system on chest roentgenogram, split cranial sutures on skull films, and enlarged subarachnoid spaces and dilated ventricles on CT scans. Two-dimensional echocardiography showed the obstructed baffle, as well as signs of redirected blood flow. Angiography and measurement of venous pressures confirmed the obstruction, and surgical correction was successful. Follow-up CT scans showed resolution of the hydrocephalus. Increased venous pressure, leading to decreased CSF absorption and increased intraventricular and subarachnoid CSF accumulation in an infant with an expandable cranium, is a possible explanation for the development of cranial enlargement and hydrocephalus under these circumstances.


A look at the thoracic surgery workforce in Canada: how demographics and scope of practice may impact future workforce needs.
The purpose of this study is to describe the demographics, training and practice characteristics of physicians performing thoracic surgery across Canada to better assess workforce needs. We developed a questionnaire using a modified Delphi process to generate questionnaire items. The questionnaire was administered to all Canadian thoracic surgeons via email (n = 102) or mail (n = 35). In all, 97 surgeons completed the survey (71% response rate). The mean age of respondents was 47.7 (standard deviation 9.1) years; 10.3% were older than 60. Ninety respondents (88.7%) were men, 95 (81.1%) practised in English and 93 (76%) were born in Canada. Most (90.4%) had a medical school affiliation, with an equal proportion practising in community or university teaching hospitals. Only 18% of respondents reported working fewer than 60 hours per week, and 34% were on call more than 1 in 3. Three-quarters of work hours were devoted to clinical care, with the remaining time split among research, administration and teaching. Malignant lung disease accounted for 61.2% of practice time, with the remaining time equally split between benign and malignant thoracic diseases. Preoperative testing (49.4%) and insufficient operating time (49.5%) were the most common factors delaying delivery of care. More than 80% of respondents reported being satisfied with their careers, with 62.1% planning on retiring after age 60. This survey characterizes Canadian thoracic surgeons by providing specific demographic, satisfaction and scope of practice information. Despite challenges in obtaining adequate resources for providing timely care, job satisfaction remains high, with a balanced workforce supply and demand anticipated for the foreseeable future.


The Pharmacoresistant Epilepsy: An Overview on Existant and New Emerging Therapies.
Epilepsy is one of the most common neurological chronic disorders, with an estimated prevalence of 0. 5 - 1%. Currently, treatment options for epilepsy are predominantly based on the administration of symptomatic therapy. Most patients are able to achieve seizure freedom by the first two appropriate drug trials. Thus, patients who cannot reach a satisfactory response after that are defined as pharmacoresistant. However, despite the availability of more than 20 antiseizure medications (ASMs), about one-third of epilepsies remain drug-resistant. The heterogeneity of seizures and epilepsies, the coexistence of comorbidities, and the broad spectrum of efficacy, safety, and tolerability related to the ASMs, make the management of these patients actually challenging. In this review, we analyze the most relevant clinical and pathogenetic issues related to drug-resistant epilepsy, and then we discuss the current evidence about the use of available ASMs and the alternative non-pharmacological approaches.


Further exploring the brain-skin connection: stress worsens dermatitis via substance P-dependent neurogenic inflammation in mice.
A neurogenic component in atopy and allergy is evident and potentially of great pathogenic relevance. Stress was recently shown to activate elements of this component and is vividly discussed as a cause of exacerbation. However, to date, scientific proof of stress-induced neuronal plasticity and neuro-immune interaction in atopy or allergy remains lacking. Here we show early evidence that exposure to sound stress and atopic dermatitis-like allergic dermatitis (AD) equipotently raise the number of cutaneous nerve fibers containing the prototypic stress neuropeptide substance P (SP) in mice. Stress increases AD readout parameters by at least 30% (eosinophil infiltration, vascular cell adhesion molecule-positive blood vessels, epidermal thickness). This dramatic pathologic exacerbation is associated with increased neurogenic inflammation (degranulated mast cells; interstitial neuropeptidergic dense core granules, mast cell apoptosis, endothelial gaping). Key features of AD exacerbation could not be induced in mice lacking the neurokinin-1 SP receptor (NK1). Interestingly, stress had no significant additional effect on CD4+ cell number, but shifted the cytokine profile toward TH2 in skin. Thus, we conclude that stress primarily exacerbates AD via SP-dependent cutaneous neurogenic inflammation and subsequent local cytokine shifting and should be considered as a therapeutic target, while it offers a convincing pathogenic explanation to affected patients and their frustrated physicians alike.


Psychotropic medication in chronic spinal disorders.
Optimal treatment of nonmalignant chronic spinal disorders (CSDs) may require the use of one or more nonopioid psychotropic medications. Vast research literature has documented high rates of psychiatric disorders in patients with CSDs. Psychotropic medications are one type of effective treatment for these disorders. Many medications of this type are also used as adjuvants to primary analgesic medications. Physicians treating CSDs may have little training and experience in prescribing psychotropic medications. Further, they may possess limited information about the efficacy of these types of medications in treating psychiatric disorders comorbid with CSDs or as adjunctive analgesics. Because of the wide variety (antidepressants, anxiolytics, sleep-promoting agents, anticonvulsants, neuroleptics, muscle relaxants) and numerous indications for psychiatric medications, a concise review of the use of psychotropic medications with CSD patients is offered for the spine specialist. A systematic review of the contemporary English literature on psychotropic medications in the CSD population. A computerized search of MEDLINE was performed on all English literature published from 1982 to August 2002. Psychotropic medications have been found to be very efficacious in the large subgroup of patients with CSDs with psychiatric comorbidity, particularly patients with the common constellation of depression, anxiety, excessive somatic complaints, insomnia and irritability. Although the type of medication indicated depends on the particular psychiatric syndrome(s), antidepressants have been found to be extremely useful with the constellation described above. There is less evidence to support the use of nonopioid psychotropic medications in the treatment of nociceptive pain, although clinical experience indicates that some individuals demonstrate a marked analgesic response. Research support for the efficacy of particular psychotropic medications in treating neuropathic pain is stronger, although more controlled research is clearly needed. Psychotropic medications are extremely useful in the treatment of psychiatric disorders comorbid with CSDs and modestly useful as analgesic adjuvants, particularly with pain of neuropathic etiology. Familiarity with these medications will aid the primary treating physician in optimizing outcomes in this difficult group of patients.


Recombinant protective antigen anthrax vaccine improves survival when administered as a postexposure prophylaxis countermeasure with antibiotic in the New Zealand white rabbit model of inhalation anthrax.
Inhalation anthrax is a potentially lethal form of disease resulting from exposure to aerosolized Bacillus anthracis spores. Over the last decade, incidents spanning from the deliberate mailing of B. anthracis spores to incidental exposures in users of illegal drugs have highlighted the importance of developing new medical countermeasures to protect people who have been exposed to "anthrax spores" and are at risk of developing disease. The New Zealand White rabbit (NZWR) is a well-characterized model that has a pathogenesis and clinical presentation similar to those seen in humans. This article reports how the NZWR model was adapted to evaluate postexposure prophylaxis using a recombinant protective antigen (rPA) vaccine in combination with an oral antibiotic, levofloxacin. NZWRs were exposed to multiples of the 50% lethal dose (LD(50)) of B. anthracis spores and then vaccinated immediately (day 0) and again on day 7 postexposure. Levofloxacin was administered daily beginning at 6 to 12 h postexposure for 7 treatments. Rabbits were evaluated for clinical signs of disease, fever, bacteremia, immune response, and survival. A robust immune response (IgG anti-rPA and toxin-neutralizing antibodies) was observed in all vaccinated groups on days 10 to 12. Levofloxacin plus either 30 or 100 μg rPA vaccine resulted in a 100% survival rate (18 of 18 per group), and a vaccine dose as low as 10 μg rPA resulted in an 89% survival rate (16 of 18) when used in combination with levofloxacin. In NZWRs that received antibiotic alone, the survival rate was 56% (10 of 18). There was no adverse effect on the development of a specific IgG response to rPA in unchallenged NZWRs that received the combination treatment of vaccine plus antibiotic. This study demonstrated that an accelerated two-dose regimen of rPA vaccine coadministered on days 0 and 7 with 7 days of levofloxacin therapy results in a significantly greater survival rate than with antibiotic treatment alone. Combination of vaccine administration and antibiotic treatment may be an effective strategy for treating a population exposed to aerosolized B. anthracis spores.


Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.
This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.


[Analysis and spatial description to correlative factors on food hygiene appeal and food poison in restaurants of city zone in Qingdao].
To study some factors that affected food poison and appeals in restaurants which were hidden danger on the cards. Data on food hygiene events from 2002 to 2004 in restaurants of 14 blocks which were located in the important city zone of Qingdao were collected and studied. The spatial distribution was conducted by means of Geographic Information System (GIS). Possible factors related to food hygiene events were investigated and analysed by NCSS Data statistics software. information of every block were marked on digitalized map by ARCVIEW3.2a software in order to show the spatial distribution of food hygiene events palpably in different areas in the course of three years. It was showed that air temperature, humidity, sunlight length were the important factors of food poison. Average amount of guests and floating population related to administration level of sanitation, the level of sanitation administration, geography location, business status of restaurants related to their status of food sanitation. This study showed the method that analysed and studied status of food sanitation from different areas by GIS were effective, simple and palpable.


[Major ion chemistry of surface water in the upper reach of Shule River Basin and the possible controls ].
To analyze the major ion chemistry of water in the upper reach of the Shule River Basin and possible controls, samples of river water, groundwater, precipitation, melt water were collected and methods including descriptive statistics, Gibbs Figure, Piper Triangular diagrams of anions and cations were comprehensive used. Results showed that the major ion compositions and hydrochemical types were significantly different in different waters such as stream water, groundwater and precipitation. The total dissolved solid (TDS) in the river water ranges between 51.7 to 432. 3 mgL-1 with an average of 177.7 mgL-1. The major cations of river water are Ca2+ and Mg2+, accounting for 45% and 31% of the cations respectively. Meanwhile, HCO(3)- constituted about 75% of the anions. The hydrochemical type of river water is HCO(-)(3)-Ca2+-Mg2+. Owing to the interaction between the river and layer, the concentration of SO(2-)4 is relatively higher. Comparing major ion concentrations of the river water with local groundwater and precipitation, concentrations of the river water ranged between precipitation and groundwater but were much closer to the concentration of groundwater, indicating that the surface water was recharged by a mixture of precipitation and groundwater while groundwater is dominant. The chemical composition of surface water samples located in the middle and a bit upper of Gibbs model, which indicates that the major chemical process of river water is controlled by rock weathering and evaporation-crystallization but rock weathering plays a much more important role.


Testosterone metabolism in the estuarine mysid neomysis integer (Crustacea; Mysidacea): identification of testosterone metabolites and endogenous vertebrate-type steroids.
Testosterone metabolism by Neomysis integer (Crustacea; Mysidacea) was assessed to obtain initial data on its metabolic capacity. N. integer were exposed to both testosterone and [(14)C]testosterone. Identification of testosterone metabolites and endogenous steroids was performed using thin-layer chromatography and liquid chromatography with multiple mass spectrometry. Endogenous production of testosterone in mysids was detected for the first time. N. integer were exposed to testosterone and metabolized administered testosterone extensively. At least 11 polar testosterone metabolites (R(f,metabolite) < R(f,testosterone)), androstenedione, dihydrotestosterone, and testosterone were produced in vivo by N. integer. A sex-specific testosterone metabolism was also observed, although this observation requires further confirmation. The anabolic steroid beta-boldenone was also identified for the first time in invertebrates. The metabolic pathway leading to the formation of beta-boldenone remains unknown, since the steroidal precursor androstadienedione could not be detected. These results reveal interesting similarities in enzyme systems in invertebrate and vertebrate species. Alterations in steroid hormone metabolism may be used as a new biomarker for the effects of endocrine disruptors in invertebrates.


Biomechanical characterization of a fibrinogen-blood hydrogel for human dental pulp regeneration.
In dental practice, Regenerative Endodontic Treatment (RET) is applied as an alternative to classical endodontic treatments of immature necrotic teeth. This procedure, also known as dental pulp revitalization, relies on the formation of a blood clot inside the root canal leading to the formation of a reparative vascularized tissue similar to dental pulp, which would provide vitality to the affected tooth. Despite the benefit of this technique, it lacks reproducibility due to the fast degradation and poor mechanical properties of blood clots. This work presents a method for constructing a fibrinogen-blood hydrogel that mimics the viscoelastic properties of human dental pulp while preserving the biological properties of blood for application in RET. By varying the blood and fibrinogen concentrations, gels with different biomechanical and biological properties were obtained. Rheology and atomic force microscopy (AFM) were combined to study the viscoelastic properties. AFM was used to evaluate the elasticity of human dental pulp. The degradation and swelling rates were assessed by measuring weight changes. The biomimetic properties of the gels were demonstrated by studying the cell survival and proliferation of dental pulp cells (DPCs) for 14 days. The formation of an extracellular matrix (ECM) was assessed by multiphoton microscopy (MPM). The angiogenic potential was evaluated by an ex vivo aortic ring assay, in which the endothelial cells were observed by histological staining after migration. The results show that the Fbg-blood gel prepared with 9 mg ml-1 fibrinogen and 50% blood of the Fbg solution volume has similar elasticity to human dental pulp and adequate degradation and swelling rates. It also allows cell survival and ECM secretion and enhances endothelial cell migration and formation of neovessel-like structures.


Host epithelial interactions with Helicobacter pylori: a role for disrupted gastric barrier function in the clinical outcome of infection?
Infection of the human stomach with Helicobacter pylori may develop into gastritis, ulceration, adenocarcinoma and mucosal lymphomas. The pathogenic mechanisms that determine the clinical outcome from this microbial-epithelial interaction remain poorly understood. An increasing number of reports suggests that disruptions of epithelial barrier function may contribute to pathology and postinfectious complications in a variety of gastrointestinal infections. The aim of this review is to critically discuss the implications of H pylori persistence on gastric disease, with emphasis on the role of myosin light chain kinase, claudins and matrix metalloproteinases in gastric permeability defects, and their contribution to the development of cancer. These mechanisms and the associated signalling events may represent novel therapeutic targets to control disease processes induced by H pylori, a microbial pathogen that colonizes the stomach of over 50% of the human population.


Agonist-independent effects of muscarinic antagonists on Ca2+ and K+ currents in frog and rat cardiac cells.
1. The whole-cell patch clamp and intracellular perfusion techniques were used for studying the effects of atropine and other muscarinic acetylcholine receptor (mAChR) antagonists on the L-type calcium currents (ICa) in frog and rat ventricular myocytes, and on the mAChR-activated K+ current (IK(ACh)) in frog atrial myocytes. 2. In frog ventricular myocytes, atropine (0.1 nM to 1 microM) reversed the inhibitory effect of acetylcholine (ACh, 1 nM) on ICa previously stimulated by isoprenaline (Iso, 2 microM), a beta-adrenergic agonist. However, in the concomitant presence of Iso, ACh and atropine, ICa was > 50% larger than in Iso alone. 3. The effects of atropine were then examined in the absence of mAChR agonists. After a preliminary stimulation of ICa with Iso (0.1 or 2 microM), atropine induced a dose-dependent stimulation of ICa. EC50 (i.e. the concentration of atropine at which the response was 50% of the maximum) and Emax (i.e. maximal stimulation of ICa expressed as percentage increase in ICa with respect to the level in Iso alone) were respectively 0.6 nM and 35%. The stimulatory effect of atropine on ICa was not voltage dependent. 4. Atropine (1 microM) had no effect on frog ICa (i) under basal conditions, (ii) upon stimulation of ICa by the dihydropyridine agonist (-)-Bay K 8644 (1 microM), or (iii) when ICa had been previously stimulated by intracellular perfusion with cyclic AMP (3 microM). However, atropine increased ICa after a stimulation by forskolin (0.3 microM). Therefore, an increased adenylyl cyclase activity was required for atropine to produce its stimulatory effect on ICa. 5. The order of potency of mAChR antagonists to reverse the inhibitory effect of ACh on Iso elevated ICa in frog ventricle was atropine > AF-DX 116 >> pirenzepine. In the absence of ACh, mAChR antagonists produced their stimulatory effect on Iso elevated ICa with the same order of potency. 6. Intracellular substitution of Gpp(NH)p (5'-guanylylimidiphosphate) for GTP (420 microM) induced a strong inhibition of frog ICa in the presence of Iso (2 microM). This effect was attributed earlier to the spontaneous and irreversible activation of the GTP-binding regulatory protein (G protein), Gi, responsible for adenylyl cyclase inhibition. Atropine (1 microM) slowed down by a factor of 2 the rate of ICa inhibition induced by Gpp(NH)p. 7. In frog atrial myocytes, intracellular perfusion with 1 mM Gpp(NH)p induces spontaneous activation of IK(ACh). This effect was attributed earlier to the spontaneous and irreversible activation of the G protein, GK.(ABSTRACT TRUNCATED AT 400 WORDS)


A simple rapid method for isolating soluble fibrin complexes from fibrinogen by treatment with thrombin and t-AMCHA.
Using treatment with thrombin associated with trans-aminomethylcyclohexane carboxylic acid (t-AMCHA), a simple and rapid method for isolating soluble fibrin complexes (SFC) from fibrinogen in the plasma was developed. By this procedure, the recovery rates of SFC and early FDP (mainly X) increased according to the concentration of t-AMCHA, reaching a maximum at 286 mM t-AMCHA. On the other hand, the recovery rate of fibrinogen remained below 1.5% and that of late FDP was almost 100% at all concentrations of t-AMCHA. These results suggested that SFC and FDP could be isolated from fibrinogen by thrombin and t-AMCHA (286 MM) treatment. Moreover, it was possible to isolate SFC from FDP using gel filtration after treatment with thrombin and t-AMCHA. The SFC could be quantified by assay of the eluted fractions containing SFC by the staphylococcal clumping test.


Differentiation of Human Mesenchymal Stem Cells Toward Quality Cartilage Using Fibrinogen-Based Nanofibers.
Mimicking the complex intricacies of the extra cellular matrix including 3D configurations and aligned fibrous structures were traditionally perused for producing cartilage tissue from stem cells. This study shows that human adipose derived mesenchymal stem cells (hADMSCs) establishes significant chondrogenic differentiation and may generate quality cartilage when cultured on 2D and randomly oriented fibrinogen/poly-lactic acid nanofibers compared to 3D sandwich-like environments. The adhering cells show well-developed focal adhesion complexes and actin cytoskeleton arrangements confirming the proper cellular interaction with either random or aligned nanofibers. However, quantitative reverse transcription-polymerase chain reaction analysis for Collagen 2 and Collagen 10 genes expression confirms favorable chondrogenic response of hADMSCs on random nanofibers and shows substantially higher efficacy of their differentiation in 2D configuration versus 3D constructs. These findings introduce a new direction for cartilage tissue engineering through providing a simple platform for the routine generation of transplantable stem cells derived articular cartilage replacement that might improve joint function.


The Combination of MBP and BCG-Induced Dendritic Cell Maturation through TLR2/TLR4 Promotes Th1 Activation In Vitro and Vivo.
To explore whether TLR2/TLR4 could be involved in the maturation of dendritic cells and polarization of CD4+ T cells induced by dendritic cells stimulated with MBP and BCG, in vitro and in vivo experiments using TLR2-/- or TLR4-/- mice were employed. MBP and BCG elevated CD80, CD86 and MHC class II expressed on dendritic cells and increased IL-12 protein, induced DC maturation, and indirectly promoted Th1 activation. Moreover, MBP and BCG upregulated costimulatory molecules on DCs in a TLR2- and TLR4-dependent manner. The levels of IFN-γ, IL-4, and IL-10 in CD4+ T cells cocultured with dendritic cells from different types of mice were determined with ELISPOT or ELISA method. TLR2/TLR4 is important in the maturation and activation of dendritic cells and the activation of Th1 cells induced by stimulation with MBP and BCG. In conclusion, TLR2 and TLR4 play an important role in the upregulation of costimulatory molecules and MHC class II molecules on dendritic cells and the activation of Th1 cells induced by stimulation with MBP and BCG. The results above indicate that the combination of MBP and BCG induced the maturation and activation of dendritic cells and promoted Th1 activation via TLR2/TLR4.


Protective effect of resveratrol against pentylenetetrazole-induced seizures and its modulation by an adenosinergic system.
The effect of trans-resveratrol (resveratrol), a polyphenolic compound with potent antioxidant activity, was investigated against pentylenetetrazole (PTZ) induced seizures in rats. Resveratrol (20, 40, and 80 mg/kg i.p.) administered 20 min prior to convulsive challenge with PTZ (60 mg/kg i.p.) dose dependently reduced the percent incidence of generalized tonic-clonic convulsions. Resveratrol (40 mg/kg) also potentiated the effect of sodium valproate (150 mg/kg) and diazepam (2 mg/kg) against PTZ-induced seizures. Since adenosine, an endogenous anticonvulsant, has been demonstrated to modulate the action of various antiepileptics, experiments were also carried out to determine whether an adenosinergic mechanism is involved in the anticonvulsant action of resveratrol. When a subanticonvulsant dose of adenosine (500 mg/kg) was administered together with resveratrol, a significant reduction in the percent incidence of generalized tonic-clonic convulsions was observed. Moreover, the nonspecific adenosine receptor antagonist theophylline (50 mg/kg i.p.) significantly reversed the resveratrol-induced protection, whereas the specific adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine (1 mg/kg i.p.) could not reverse the resveratrol-induced protection. The findings of the present study suggest an antiepileptic potential of resveratrol and that an adenosinergic mechanism may play a role in its anticonvulsant activity.


Urgent radiotherapy is effective in the treatment of metastatic medulloblastoma causing symptomatic brainstem edema.
A 3-year-old male who presented with hydrocephalus symptoms was found to have metastatic medulloblastoma with diffuse spinal disease. Thirteen days following surgical resection of his primary tumor, he clinically deteriorated due to worsening brainstem edema. Following intubation, stress-dose steroids, and mannitol, urgent radiotherapy was initiated to the whole brain and cervical cord. The patient improved clinically with a repeat MRI showing decreased leptomeningeal enhancement in the radiation fields. In the literature, there are no reports of successful urgent radiotherapy in medulloblastoma, but in this instance, it proved to be a viable option.


A case report: familial hypoalphalipoproteinemia.
We studied an 8 year-old girl whose height was 129 cm (25-50th percentile), weight 30 kg (75th percentile), blood pressure 115/75 mm Hg (75th percentile) and had a calcified mass lesion in the left posterior mediastinum. In the histopathological investigation of this mass lesion, symptoms of complicated atherosclerosis, such as mural thrombus and diffused calcification, were observed. Lipid investigations were performed in this patient whose total cholesterol and triglyceride levels were in the normal ranges. HDL-cholesterol, apoprotein A-I and alpha band were low without any other lipid and lipoprotein abnormalities. During one year, in her monthly lipid analysis the mean levels of HDL-cholesterol, apoprotein A-I and alpha band were found to be 0.73 +/- 0.11 mmol/l, 90 +/- 20 mg/dl and 23 +/- 5% respectively. Studies of her family revealed low levels of HDL-cholesterol, apoprotein A-I and alpha band in her mother and sister. We describe our investigation of this rare case of familial hypoalphalipoproteinemia.


Efficacy and safety of multidrug therapy in paucibacillary leprosy in Singapore.
A total of 49 patients with paucibacillary leprosy (PB) who completed multidrug therapy (MDT) between 1985 and 1990 were analysed retrospectively for efficacy and complications; 20 (40.8%) patients had borderline-tuberculoid (BT), 13 (26.5%) had tuberculoid (TT), 1 (2.1%) had indeterminate (I) and 15 (30.0%) had pure neural (N) leprosy; 26 patients (76.5% of 34 non-neural leprosy) were skin biopsied for histological cure before MDT was stopped. Of these 26 patients, 19 had histological clearance at 6 months while the remaining 7 cleared beyond 1 year (18-36 months). The remaining 8 non-neural patients who refused rebiopsy had MDT for 6-8 months and the MDT was stopped when there was clinical clearance. Of the 15 neural (N) leprosy patients, 11 were given MDT for 6 months while the rest had 12-18 months of treatment; 1 patient with neural leprosy, who was treated for 6 months, relapsed with BT leprosy 18 months post-treatment. There were few complications among the 49 patients-4 (8.2%) patients developed reaction to dapsone, 1 (2.0%) had the dapsone syndrome, 2 (4.1%) had haemolytic anaemia and 1 (2.0%) had dapsone hepatitis; 7 (14.3%) patients had type I reaction.


Selecting the C7-LIV Line Vertebra as the Upper Instrumented Vertebra for Adolescent Idiopathic Scoliosis Lenke Type 1A Curves: Multicenter and a Minimum 2-Year Follow-up Study.
Retrospective multicenter cohort study. We evaluated a new upper instrumented vertebra (UIV) selection method that used the modified Shinshu line (MSL) to establish the selected UIV as the MSL vertebra (MSLV). No reports have addressed optimal UIV selection according to the lower instrumented vertebra (LIV) for good trunk balance in Lenke 1A curves. Forty-five consecutive patients (44 female, 14.4 ± 2.4 yrs) receiving posterior spinal fusion (PSF) for a Lenke 1A adolescent idiopathic scoliosis (AIS) curve were analyzed. We defined the novel MSL as the line between the center of the spinous process of C7 and that of the spinous process of the LIV. The vertebral body with which the MSL first contacted proximally was defined as the MSLV. The groups in which the UIV was at, proximal to, or distal to the MSLV were defined as the matched group (M-group; 15 cases [15 female], 14.7 ± 2.1 yrs), proximal group (P-group; 20 cases, [19 female], 15.0 ± 2.2 yrs), and distal group (D-group; 10 case [10 female], 14.8 ± 2.5 yrs), respectively. We measured Cobb angle, main thoracic (MT) curve correction rate, and C7 plumb line absolute value (C7PL) at pre- and 2 years postoperatively for comparisons using Dunnett test, with the M-group as the control. In the M-group, P-group, and D-group, the Cobb angle correction rate between pre- and postoperative time points were 65.3 ± 1.3%, 62.4 ± 1.6%, and 52.8 ± 6.8%, respectively, and comparable apart from a smaller correction tendency in the D-group versus the M-group (P = 0.08). At 2 years postoperatively, C7PL was 0.5 ± 0.4, 1.0 ± 0.6, and 1.3 ± 0.9 cm, respectively, and significantly smaller for the M-group (both P < 0.05). Better trunk balance were obtained without reducing correction rate by setting the novel MSLV as the UIV in PSF for Lenke type 1A curves. 3.


Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study.
Many genetic alterations that are associated with the prognosis of acute myeloid leukemia (AML) have been identified, and several risk stratification systems based on the genetic status have been recommended. The European LeukemiaNet (ELN) first proposed the risk stratification system for AML in 2010 (ELN-2010), and recently published the revised system (ELN-2017). We validated the long-term prognosis and clinical characteristics of each ELN-2017 risk category in Japanese adult AML patients who were treated in the Japan Adult Leukemia Study Group (JALSG) AML-201 study. We demonstrated that the 3-risk category system of the ELN-2017 successfully discriminated the overall survival and complete remission rates in our cohort in comparison with the 4-risk category of the ELN-2010. However, there were still genetic categories in which stratification of patients into favorable or intermediate risk categories was controversial; the low allelic ratio of FLT3-ITD was not necessarily associated with a better prognosis in patients with FLT3-ITD, and cytogenetic abnormalities may affect the prognosis in patients with favorable genetic lesions such as NPM1 and CEBPA mutations. As many molecular targeting agents, such as FLT3 inhibitors, have been developed, we must continue to modify the genetic risk stratification system to match the progression of therapeutic strategies.


Analysis of the course of rheumatoid arthritis depending on the climatic and geographic zones of Uzbekistan.
The aim of this study was to evaluate the features of rheumatoid arthritis (RA) as well as other health problems and treatment necessities in various climatic and geographic zones of Uzbekistan. The data on 2013 patients with a confirmed diagnosis of RA were collected retrospectively. The results showed that the Khorezm and Surkhandarya regions dominated by indicators of disease activity and severity, such as a more expressed progressive course; in addition, marked alterations in the reproductive system, especially in women, were observed as well. In contrast, patients from the Namangan and Tashkent zones were characterized by relatively better parameters of interest. In conclusion, the differences in climatic and geographic zones in Uzbekistan may be important for patients with RA. More in-depth studies are needed to get a more accurate insight into the possible influence of climate and environmental factors on RA.


Fracture Resistance of Internal Conical and External Hexagon: Regular and Narrow Implant-Abutment Assemblies.
The aim of this study was to compare the maximum load on the elastic limit of internal conical (IC) implants with regular external hexagon (REH) and narrow external hexagon (NEH) implants. Thirty cylindrical implants were divided in 3 groups (n = 10): REH (3.75 mm); NEH (3.3 mm); IC (3.5 mm). The implants were evaluated by means of cantilever bending loads using a mechanical testing machine. A strain qualitative analysis and the corresponding angles were analyzed. Using single factor analysis of variance with Tukey Test and Friedman Test (P < 0.05) the statistical analysis for data were performed. REH (294.37 N) and IC (294.37 N) groups presented statistically greater Fle than NEH (189.16 N). Regarding to the strain, there were no significant differences among groups. However, there were a greater number of fissures and more fractures present on NEH group. The IC implant with smaller diameter did not result in reduction of elastic limit when compared with the REH implants. Nevertheless, the reduction of 0.45 mm of the hexagonal connection implant's diameter has significantly diminished the elastic limit.


Kinetics of macrophages, myofibroblasts and mast cells in carbon tetrachloride-induced rat liver cirrhosis.
Recently, activation of macrophages, myofibroblasts and mast cells have been thought to be associated with liver fibrosis. The present study investigated the kinetics of these cells and the numeric relationship in carbon tetrachloride (CCl4)-induced rat liver cirrhosis. Macrophages and myofibroblasts were observed with immunohistochemistry and mast cells were detected by toluidine blue. Mast cells increased in proportion to the development of fibrosis with a maximum number on week 14. The numbers of macrophages and myofibroblasts increased during weeks 0 to 10 but decreased from weeks 12 to 14. The numbers of macrophages and myofibroblasts increased in the development of fibrosis but decreased when cirrhosis was induced. However, mast cells increased in both. Therefore, there was a numerical relationship among the numbers of macrophages, myofibroblasts and mast cells in liver fibrosis but none between the former two cells and the mast cells in liver cirrhosis.


All-Cause Mortality Amongst Patients Undergoing Above and Below Knee Amputation in a Regional Vascular Centre within 2014-2015.
Major lower limb amputation remains a common treatment for patients with peripheral vascular disease (PVD) in whom other measures have failed. It has been associated with high morbidity and mortality, including risks from venous thromboembolism (VTE). A two-year retrospective cohort study was conducted involving 79 patients who underwent major lower limb amputation (below- or above-knee amputation) between January 2014 and December 2015 in a single tertiary referral centre. Amputation procedures were performed for reasons relating to complications of PVD and/or diabetes mellitus. Patients were followed-up to investigate all-cause mortality rates and VTE events using the Northern Ireland Electronic Care Record database (mean follow-up time 17 months). Of the 79 patients, there were 52 male and 27 female. Mean age at time of surgery was 72 years (range 34-99 years). Forty-six patients (58%) suffered from diabetes mellitus, 29 (35%) heart failure, 31 (39%) chronic kidney disease (CKD) and 10 (13%) chronic obstructive pulmonary disease (COPD). Twenty patients (25%) were on anticoagulant therapy, and 53 (67%) were on antiplatelet therapy.Thirty-five patients (44%) died during follow-up; mean age at death was 74 years. No statistically significant association was found between mortality rate and the level of amputation (p=0.3702), gender (p=0.3507), or comorbid diabetic mellitus (p=0.1127), heart failure (p=0.1028), CKD (p=0.0643) or COPD (p=0.4987).Two patients experienced radiologically-confirmed non-fatal pulmonary emboli and two patients developed radiologically-confirmed deep vein thrombosis. The results are in agreement with current literature that amputation is associated with significant mortality, with almost half of the study population dying during follow-up. Further work should explore measures by which mortality rates may be reduced.


On-again/off-again dating relationships: what keeps partners coming back?
Building on research comparing on-again/off-again (on-off) relationships to other dating relationships, the current study focused on a unique feature of these relationships-renewals. A sample of 274 participants who had experienced an on-off relationship completed a survey about why they renewed their relationships, characteristics of their breakups and renewals, and what stressors and benefits they experienced. These characteristics were used to predict the occurrence of renewals, separately as well as in multivariate analyses. In addition to lingering feelings being a predominant reason for renewals, findings suggested uncertainty about what the preceding breakup indicated, not having dated others after breakups, and feeling the on-off nature improved the relationship were all related to an increased chance of renewals. Mutual initiations of breakups, as well as reporting uncertainty about the general nature of the relationship, were also related to a decreased chance of renewals.


Temporal and spatial changes in persistent organic pollutants in Vietnamese coastal waters detected from plastic resin pellets.
Plastic resin pellets collected at Minh Chau island and Ba Lat estuary between 2007 and 2014 in Vietnam were analyzed for dichloro-diphenyl-trichloroethanes (DDTs), polychlorinated biphenyls (PCBs) and hexachlorocyclohexanes (HCHs). The study was carried out as part of the International Pellet Watch program for monitoring the global distribution of persistent organic pollutants (POPs). Higher levels of DDTs compared to PCBs indicated agricultural inputs rather than industrial discharges in the region. Most POP concentrations on both beaches decreased over the period, with the exception of HCH isomers. Though the concentration of DDTs showed a drastic decline on both beaches between 2007/2008 and 2014, DDTs accounted for 60-80% of total DDTs, suggesting that there is still a fresh input of these chemicals in the region. This study strongly recommends further investigations to track temporal and spatial patterns of POP levels in the marine environment using plastic resin pellets.


Actively learning object names across ambiguous situations.
Previous research shows that people can use the co-occurrence of words and objects in ambiguous situations (i.e., containing multiple words and objects) to learn word meanings during a brief passive training period (Yu & Smith, 2007). However, learners in the world are not completely passive but can affect how their environment is structured by moving their heads, eyes, and even objects. These actions can indicate attention to a language teacher, who may then be more likely to name the attended objects. Using a novel active learning paradigm in which learners choose which four objects they would like to see named on each successive trial, this study asks whether active learning is superior to passive learning in a cross-situational word learning context. Finding that learners perform better in active learning, we investigate the strategies and discover that most learners use immediate repetition to disambiguate pairings. Unexpectedly, we find that learners who repeat only one pair per trial--an easy way to infer this pair-perform worse than those who repeat multiple pairs per trial. Using a working memory extension to an associative model of word learning with uncertainty and familiarity biases, we investigate individual differences that correlate with these assorted strategies.


Synergy between interleukin-1β, interferon-γ and glucocorticoids to induce TLR2 expression involves NF-κB, STAT1 and GR.
Glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to downregulate inflammatory gene expression and are effective treatments for mild-moderate asthma. However, in severe asthma and virus-induced exacerbations, glucocorticoid therapies are less efficacious, possibly due to reduced repressive ability and/or the increased expression of pro-inflammatory genes. In human A549 epithelial and primary human bronchial epithelial cells (pHBECs), toll-like receptor (TLR) 2 mRNA and protein were supra-additively induced by interleukin-1β (IL1B) plus dexamethasone (IL1B+Dex), interferon-γ (IFNG) plus dexamethasone (IFNG+Dex) and IL1B plus IFNG plus dexamethasone (IL1B+IFNG+Dex). Indeed, ~34-2100-fold increases were apparent at 24 h for IL1B+IFNG+Dex and this was greater than for any single or dual treatment. Using the A549 cell model, TLR2 induction by IL1B+IFNG+Dex was antagonized by Org34517, a competitive GR antagonist. Further, when combined with IL1B, IFNG, or IL1B+IFNG, the enhancements by dexamethasone on TLR2 expression required GR. Likewise, inhibitor of κB kinase 2-inhibitors reduced IL1B+IFNG+Dex-induced TLR2 expression, and TLR2 expression induced by IL1B+Dex, with or without IFNG, required the nuclear factor (NF)-κB subunit, p65. Similarly, signal transducer and activator of transcription (STAT) 1 phosphorylation and γ-interferon-activated-sequence-dependent transcription were induced by IFNG. These, along with IL1B+IFNG+Dex-induced TLR2 expression, were inhibited by Janus kinase (JAK) inhibitors. As IL1B+IFNG+Dex-induced TLR2 expression also required STAT1, this study reveals cooperation between JAK-STAT1, NF-κB, and GR to upregulate TLR2 expression. Since TLR2 agonism elicits inflammatory responses, we propose that synergies involving TLR2 may occur within the cytokine milieu present in the immunopathology of glucocorticoid-resistant disease, and this could promote glucocorticoid resistance. Significance Statement This study highlights that in human pulmonary epithelial cells, glucocorticoids, when combined with the inflammatory cytokines, IL1B and IFNG, can synergistically induce the expression of inflammatory genes, such as TLR2. This effect involved positive combinatorial interactions between NF-κB/p65, GR and JAK-STAT1 signalling to synergistically upregulate TLR2 expression. Thus, synergies involving glucocorticoid-enhancement of TLR2 expression may occur in the immunopathology of glucocorticoid-resistant inflammatory diseases, including severe asthma.


Pearls & Oy-sters: ATX-FGF14 Mimicking Autoimmune Pathology.
ATX-FGF14 (formerly spinocerebellar ataxia 27, OMIM #193003) is an autosomal dominant condition caused by a pathogenic variant in the fibroblast growth factor 14 (FGF14, OMIM #601515) gene located on chromosome 13. The phenotypic expression can vary in patients with the same genotype, often delaying diagnosis, especially in probands without known affected relatives and/or with limited available family history. We describe 2 cases of ATX-FGF14 in 1 family with a focus on the importance of differentiating episodic manifestations of neurogenetic conditions from inflammatory/autoimmune neurologic conditions. A 68-year-old male patient (case 1) presented with episodic dysarthria, dizziness, imbalance, and encephalopathy, creating suspicion for a possible autoimmune etiology. At the first evaluation, the patient reported no significant family history. Four years later, on revisiting the family history, he noted that his 49-year-old niece (case 2) had also developed neurologic symptoms of an unclear etiology. On evaluation, she had tremor and ataxia. Both patients also had coexistent evidence of systemic autoimmunity that likely contributed to the initial suspicion of neurologic autoimmunity, and neither had cerebellar or brainstem volume loss. Ultimately, their genetic testing revealed a pathogenic structural variant in the FGF14 gene, consistent with ATX-FGF14. These 2 cases highlight the importance of a detailed interval family history at each visit, especially in undiagnosed adult patients, as well as the importance of objectively analyzing the impact of immunotherapy diagnostic treatment trials to avoid unnecessary immunomodulatory medications.


Reduction of Bromate by Cobalt-Impregnated Biochar Fabricated via Pyrolysis of Lignin Using CO2 as a Reaction Medium.
In this study, pyrolysis of lignin impregnated with cobalt (Co) was conducted to fabricate a Co-biochar (i.e., Co/lignin biochar) for use as a catalyst for bromate (BrO3-) reduction. Carbon dioxide (CO2) was employed as a reaction medium in the pyrolysis to induce desired effects associated with CO2; (1) the enhanced thermal cracking of volatile organic compounds (VOCs) evolved from the thermal degradation of biomass, and (2) the direct reaction between CO2 and VOCs, which resulted in the enhanced generation of syngas (i.e., H2 and CO). This study placed main emphases on three parts: (1) the role of impregnated Co in pyrolysis of lignin in the presence of CO2, (2) the characterization of Co/lignin biochar, and (3) evaluation of catalytic capability of Co-lignin biochar in BrO3- reduction. The findings from the pyrolysis experiments strongly evidenced that the desired CO2 effects were strengthened due to catalytic effect of impregnated Co in lignin. For example, the enhanced generation of syngas from pyrolysis of Coimpregnated lignin in CO2 was more significant than the case without Co impregnation. Moreover, pyrolysis of Coimpregnated lignin in CO2 led to production of biochar of which surface area (599 m2 g-1) is nearly 100 times greater than the biochar produced in N2 (6.6 m2 g-1). Co/lignin biochar produced in CO2 also showed a great performance in catalyzing BrO3- reduction as compared to the biochar produced in N2.


Interleukin-1beta system (ligand, receptor type I, receptor accessory protein and receptor antagonist), TNF-alpha, TGF-beta1 and neuropeptide Y mRNAs in specific brain regions during bacterial LPS-induced anorexia.
Bacterial lipopolysaccharide (LPS) or endotoxin induces neurological manifestations including anorexia. It is proposed that LPS-induced cytokine production is involved in the generation of neurological manifestations and in neuroinflammatory/immunological responses during gram-negative infections. For example, LPS-induced effects can be blocked or ameliorated by the interleukin-1 receptor antagonist (IL-1Ra). Here, sensitive and specific RNase protection assays were used to investigate the effects of the intracerebroventricular (i.c.v.) administration of LPS on mRNA levels of interleukin-1beta (IL-1beta) system components, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and neuropeptide Y (NPY) in the cerebellum, hippocampus, and hypothalamus. The same brain region sample was analyzed with all of the antisense probes. The data show simultaneous local induction of multiple cytokine components messenger ribonucleic acids (mRNAs) within specific brain regions in anorectic rats responding to i.c.v. administered LPS (500 ng/rat). Interleukin-1beta and IL-1Ra had a similar mRNA induction profile (hypothalamus > cerebellum > hippocampus). Interleukin-1 receptor type I (IL-1RI) mRNA also increased in all three brain regions examined, and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA was induced in the hypothalamus. Tumor necrosis factor-alpha mRNA levels increased in the hypothalamus > hippocampus > cerebellum. Levels of membrane bound IL-1R AcP, TGF-beta1, and NPY mRNAs did not change significantly in any brain region. The results suggest that: (1) endogenous up-regulation of IL-1beta and TNF-alpha in the hypothalamus contribute to LPS-induced anorexia; and (2) the ratio IL-1Ra/IL-1beta, and IL-1beta <--> TNF-alpha interactions may have implications for gram-negative infections associated with high levels of LPS in the brain-cerebrospinal fluid.


A study on rapid and stable catalytic reduction of 4-nitrophenol by 2-hydroxyethylamine stabilized Fe3O4@Pt and its kinetic factors.
The successful development of efficient and stable catalysts for 4-NP reduction reactions is beneficial to the environment and ecology. Fe3O4@Pt exhibits excellent catalytic performance for 4-NP reduction reaction due to the synergistic effect between Fe and Pt. But its structure and catalytic performance are extremely unstable. Here, we utilized the small-scale organic compound 2-hydroxyethylamine as surfactant to construct a stable composite nanomaterial. Then investigated the influence of monochromatic light (650 nm, 808 nm and 980 nm) and temperature on the kinetics of 4-NP reduction reaction by 2-hydroxyethylamine stabilized Fe3O4@Pt. The results indicate that both temperature and monochromatic light radiation can affect kinetic regulation. Increasing temperature can promote the catalytic rate, while monochromatic light radiation can induce agglomeration and inhibit the catalytic rate. This study opens up a new way for developing and regulating catalysts for heterogeneous catalysis reactions.


Immunocastration of Bos indicus x Brown Swiss bulls in feedlot with gonadotropin-releasing hormone vaccine Bopriva provides improved performance and meat quality.
The objective of this study was to determine the effects of a GnRH vaccine on feedlot performance and meat quality in Bos indicus Zebu × Brown Swiss bulls. The study was a 2 × 2 factorial arrangement of treatments with 1,600 bulls allocated by BW into 4 groups of ≈ 400 animals. The GnRH vaccine (Bopriva) was injected on d 0 and 42, and anabolic implants given on d 0 (Component E-S) and d 84 (Synovex Choice). Group designations were: Con = placebo control; Imp = implants alone; Vac = GnRH vaccine alone; and Vac+Imp = GnRH vaccine together with implants. The second GnRH vaccination at d 42 resulted in elevated titers of IgG antibody and suppressed concentrations of testosterone in vaccinated groups (Vac and Vac+Imp) at d 56 (P < 0.001), with titers and suppressed testosterone persisting to d 147 (P < 0.001). Groups Vac and Vac+Imp had reduced testes weights at slaughter on d 147 (P < 0.001). Bulls in group Vac were not different in final BW, HCW, or ADG (d 42 to 147) relative to bulls in group Con. Bulls in group Vac+Imp had greater final BW than bulls in group Imp (P = 0.008) and greater BW than bulls in group Vac and group Con (P < 0.001). The HCW of Vac+Imp bulls was greater than the Vac or Con bulls (P < 0.001) but was not different to the Imp bulls (P = 0.294). Improved ADG was obtained by vaccination with the GnRH vaccine, in the presence of implants (group Vac+Imp compared with group Imp, P < 0.001) or absence of implants (group Vac compared with group Con, P = 0.028). Meat quality of bulls receiving the GnRH vaccine was improved irrespective of implant status, with a 1.6- to 2.6-fold increase in the proportion of bulls in groups Vac and Vac+Imp, respectively, grading as USDA Choice (P < 0.002) and with greater fat depth at the 12th rib (P < 0.001). Meat tenderness was improved in the vaccine groups (Vac and Vac+Imp) compared with groups Con and Imp (P < 0.004). Use of the GnRH vaccine Bopriva in Bos indicus × Brown Swiss bulls finishing in a feedlot under Mexican husbandry conditions can provide improved performance in combination with implants (increased BW and ADG) and improved meat quality, with or without implants, and in particular, better USDA carcass grading and loin fat cover.


[Genetic analysis of hormone resistance].
Thyroid hormone resistance is a syndrome defined as impaired tissue response to thyroid hormone which would be excessive under normal circumstances. Although it has long been speculated that this defect was caused by an abnormality at the site of the nuclear receptor for thyroid hormone, isolation of complementary DNA encoding thyroid hormone receptors has only recently enabled us to directly examine this hypothesis. Thyroid hormone receptors are coded on two separate genes, THRA and THRB. Both genes give rise to multiple receptor subtypes through alternative splicing or different usage of promoters. Tight linkage between THRB locus and resistant phenotype was demonstrated in one affected family, and subsequently, more than 30 genetic abnormalities of the THRB gene were isolated. No abnormalities have been demonstrated on the THRA gene. Denaturing gradient gel electrophoresis was used to screen abnormalities on the THRB gene of affected families, and the results also strongly supported the hypothesis that thyroid hormone resistance is caused by an abnormal THRB gene. Molecular analysis of thyroid hormone resistance will facilitate understanding of the pathophysiology of this syndrome and the molecular mechanism of thyroid hormone action.


A composite likelihood approach in testing for Hardy Weinberg Equilibrium using family-based genetic survey data.
In population-based household surveys, for example, the National Health and Nutrition Examination Survey, households are often sampled by stratified multistage cluster sampling, and multiple individuals related by blood are often sampled within households. Therefore, genetic data collected from these population-based household surveys, called National Genetic Household Surveys, can be correlated because of two levels of correlation. One level of correlation is caused by the multistage geographical cluster sampling and the other is caused by biological inheritance among participants within the same sampled family. In this paper, we develop an efficient Hardy Weinberg Equilibrium (HWE) test utilizing pairwise composite likelihood methods that incorporate the sample weighting effect induced by the differential selection probabilities in complex sample designs, as well as the two-level clustering (correlation) effects described above. Monte Carlo simulation studies show that the proposed HWE test maintains the nominal levels, and is more powerful than existing methods (Li et al. 2011) under various (non)informative sample designs that depend on genotypes (explicitly or implicitly), family relationships or both, especially when within-household sampling depends on the genotypes. The developed tests are further evaluated using simulated genetic data based on the Hispanic Health and Nutrition Survey. Copyright © 2016 John Wiley & Sons, Ltd.


Mapping Arbovirus-Vector Interactions Using Systems Biology Techniques.
Studying how arthropod-borne viruses interact with their arthropod vectors is critical to understanding how these viruses replicate and are transmitted. Until recently, these types of studies were limited in scale because of the lack of classical tools available to study virus-host interaction for non-model viruses and non-model organisms. Advances in systems biology "-omics"-based techniques such as next-generation sequencing (NGS) and mass spectrometry can rapidly provide an unbiased view of arbovirus-vector interaction landscapes. In this mini-review, we discuss how arbovirus-vector interaction studies have been advanced by systems biology. We review studies of arbovirus-vector interactions that occur at multiple time and length scales, including intracellular interactions, interactions at the level of the organism, viral and vector populations, and how new techniques can integrate systems-level data across these different scales.


The frequency of depression and menopause-related symptoms in postmenopausal women living in a province in Eastern Turkey, and the factors that affect depressive status.
This study was designed to determine depression in women in the postmenopausal stage in Elazig city, located in Eastern Turkey, and determine the factors affecting depressive status. The sample included 546 women and of these, 519 could be contacted. A questionnaire was conducted with the women who were included in the study. This included demographic properties, which are thought to affect depression. Subjects were given the Beck Depression Inventory (BDI). In total, 97.7% of women reported that they experienced a problem or had complaints during menopause, while 54.9% reported that they experienced problems in their sexual lives. The mean BDI score of women was 17.01+/-8.75. The ratio of women whose total scores were higher than the breakpoint of 17 was 42.2%. Single, widowed, and divorced women had higher ratios than married women; primary school or lower education women had higher ratios than high school or lower education graduate women; the women who reported that they had problems in their sexual lives had higher ratios than the other women within the survey; the women who were subject to violence at any time during their lives had higher ratios than the women who had not experienced violence (P<.05). The frequency of depression symptoms in women living in Elazig is high. The information and services that the local women receive about menopause are inadequate.


Arabidopsis At5g39790 encodes a chloroplast-localized, carbohydrate-binding, coiled-coil domain-containing putative scaffold protein.
Starch accumulation and degradation in chloroplasts is accomplished by a suite of over 30 enzymes. Recent work has emphasized the importance of multi-protein complexes amongst the metabolic enzymes, and the action of associated non-enzymatic regulatory proteins. Arabidopsis At5g39790 encodes a protein of unknown function whose sequence was previously demonstrated to contain a putative carbohydrate-binding domain. We here show that At5g39790 is chloroplast-localized, and binds starch, with a preference for amylose. The protein persists in starch binding under conditions of pH, redox and Mg(+2) concentrations characteristic of both the day and night chloroplast cycles. Bioinformatic analysis demonstrates a diurnal pattern of gene expression, with an accumulation of transcript during the light cycle and decline during the dark cycle. A corresponding diurnal pattern of change in protein levels in leaves is also observed. Sequence analysis shows that At5g39790 has a strongly-predicted coiled-coil domain. Similar analysis of the set of starch metabolic enzymes shows that several have strong to moderate coiled-coil potential. Gene expression analysis shows strongly correlated patterns of co-expression between At5g39790 and several starch metabolic enzymes. We propose that At5g39790 is a regulatory scaffold protein, persistently binding the starch granule, where it is positioned to interact by its coiled-coil domain with several potential starch metabolic enzyme binding-partners.


Regulation of Rho GTPase proteins during spine structural plasticity for the control of local dendritic plasticity.
While it is generally appreciated that learning involves the structural rearrangement of neuronal circuits, the underlying orchestration of molecular events that drives these changes is not as well understood. Recent studies on the spatiotemporal organization of synaptic signaling events have provided new insights into the biochemical underpinnings of various expressions of structural neuronal plasticity, as well as the functional consequences that emerge because of the particular behavior of the molecules involved. In particular, activity patterns of and interplay among a class of morphogenic signaling proteins, the Rho GTPases, and their downstream signals, are found to be critical for linking neuronal activity with various forms of neuronal plasticity. We review recent findings on this topic and discuss their physiological implications.


Comparison of horseradish peroxidase and alkaline phosphatase-labelled antibodies in enzyme immunoassays.
The periodate method was found to be most effective for preparing horseradish peroxidase-sheep anti-human and horseradish peroxidase-donkey anti-mouse immunoglobulin (IgG) conjugates. The conjugates were improved by carrying out the oxidation of the enzyme at low pH. Anti-human and anti-mouse IgG-peroxidase conjugates (0.5 mg/mL IgG and 0.7 mg/mL IgG, respectively) were used at 1:15,000 and 1:8000 dilutions, respectively, in a sandwich ELISA to detect human and mouse IgG in buffer or in a growth medium containing 20% foetal calf serum. Using the peroxidase conjugates, it was possible to detect human and mouse IgG at concentrations as low as 1 ng/mL. The glutaraldehyde method was found to be much more effective than the periodate method for conjugating alkaline phosphatase to the antibodies. The optimum dilutions for anti/human and anti-mouse IgG-alkaline phosphatase conjugates (0.18 mg/mL IgG and 0.3 mg/mL IgG, respectively) in ELISA were 1:500 and 1:1000, respectively. The detection limit with alkaline phosphatase conjugates was 7 ng/ml for human IgG and 4 ng/ml for mouse IgG.


The analgesic efficacy of ultrasound-guided transversus abdominis plane block on postoperative pain and morphine consumption in varicocelectomy.
To evaluate the analgesic effect of transversus abdominis plane (TAP) block administered before varicocele surgery. This study was completed at the Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, between January 2011 and April 2013. In a prospective, double blind, randomized, placebo controlled clinical study, 40 male patients scheduled for elective varicocele operations were randomized to group T (treatment group) or group C (controls). After receiving general anesthesia, group T received a TAP block using 20 mL 0.25% bupivacaine on the operation side, whereas group C received a control block using 20 mL 0.9% Sodium chloride. During the first 24 hours after surgery, the patient pain was evaluated using the visual analogue scale (VAS) at rest and while coughing. Postoperative patient controlled analgesia morphine consumption, VAS scores, and side effects were recorded. Of 34 patients, Group T (n=18) had significantly lower VAS pain scores than Group C (n=16) both at rest and while coughing. The total morphine consumed was lower (7.7 ± 4.0) versus 21.6 ± 12.4 mg, p less than 0.001) in the 24 hours after surgery. As part of a multimodal analgesic regime after varicocelectomy surgery, morphine consumption and VAS pain scores were significantly lower among those receiving 20 mL 0.25% bupivacaine administered for a TAP block than among controls.


Enhanced expression of the c-myc protooncogene in human intracranial meningiomas.
We examined the alteration and expression of c-myc protooncogene in 11 human intracranial meningiomas using Southern blot, Northern blot and immunohistochemical techniques. Southern blot showed neither amplification nor rearrangement but Northern blot and immunohistochemical study revealed enhanced expression of the c-myc gene. Immunohistochemically, c-myc product was found in all of the 11 cases and seven of these cases showed an above moderate degree of immunoreaction in semiquantitative analysis. Loss of heterozygosity at IGLC2 locus on chromosome 22 was detected in four of the 8 informative cases. But extent and intensity of immunoreactivity did not correlated with loss of heterozygosity on chromosome 22. These genetic changes may play important roles in the pathogenesis of human intracranial meningioma.


Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5.
Rearrangements of the human trithorax gene (MLL, HRX, Htrx-1, All-1) were studied by Southern blotting in blast cells stored at presentation from 65 adults with de novo acute myelomonocytic (AML-M4) and acute monocytic leukemia (AML-M5). MLL rearrangements were demonstrated in 15 (23%) cases, including eight patients in whom karyotype analysis had failed to detect abnormalities of chromosome band 11q23. The patients with MLL rearrangements did not differ significantly from those with germline configurations in terms of the sex and age of the patients, the presence of lymphadenopathy, hepatosplenomegaly, or central nervous system involvement, and the absolute blast count at diagnosis. Kaplan-Meier analysis of the treated patients demonstrated no difference in survival for patients with MLL rearrangements compared with those without rearrangements. Therefore, in contrast to infantile acute leukemia, in adults with AML-M4 and AML-M5, MLL rearrangements do not identify a subgroup of patients with different clinical features or prognosis.


Patient's Perceptions Regarding Orthodontic Needs and Satisfactory Level with the Procedure.
In order to keep the patients satisfied with Orthodontic treatment and to address the growing concern among new orthodontic patients, this study was undertaken to evaluate patient's perceptions of their orthodontic treatment needs and the satisfactory level with the procedure. This cross-sectional study was conducted among a sample of 362 patients who had received orthodontic treatment. Questionnaires included information factors that encouraged them to take orthodontic treatment, painful experience of orthodontic therapy, and also to know the effectiveness of the treatment. Student's t-test and ANOVA test were used to analyze results at P = 0.05. Most of the participants faced problems due to their dentition (60.2%), followed by mastication 23.6%. It was found that most of the study subjects were motivated by orthodontist to receive the treatment (29.7%). When the participants were asked about the complications faced by them during the procedure and the most common answer was a longer duration of the treatment (23.3%). Pain was also a common factor faced by the participants (15.9%). Significant results were seen according to gender and age. The study concluded that problems in the dentition were the main factor to seek orthodontic treatment and most of the subjects were convinced by the specialist to undergo orthodontic therapy. Many problems faced during the treatment, but still majority gave a positive response to the treatment.