Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) as a parasite of pampas deer (Ozoctoceros bezoarticus) and cattle in Brazil's Central Pantanal.
In the Pantanal, domestic and wild animals share the same habitats; their parasites and environment interact in a complex and dynamic way. The Rhipicephalus (Boophilus) microplus is the most important cattle tick in Brazil. In the past two decades, some traditional management practices are being replaced with the aim of intensifying cattle production. Forested areas are being replaced by exotic pasture and ranch owners are replacing Nelore for European breeds. The pampas deer (Ozoctoceros bezoarticus) is a medium-sized cervid that occurs in grasslands of South America. Between December 2005 and January 2007, we captured and collected ticks from 15 pampas deer and 172 bovines. The abundance, intensity, and prevalence of ticks found in cattle were lower than those in pampas deer (p < 0.05), indicating that pampas deer is more susceptible than cattle. The high number of engorged females collected from pampas deer, their capacity to lay eggs, and the percentage of eclosion indicates that the pampas deer population in the Pantanal wetlands is sufficient to maintain the R. (B.) microplus, thus playing a important role in the transmission of ticks and tick-borne diseases. The recent deforestation to introduce Brachiaria sp. and European cattle needs to be carefully evaluated to prevent economic losses to the cattle industry and damage to the wildlife in Pantanal.


Efficacy of new retinoids in the prevention of mammary cancers and correlations with short-term biomarkers.
A number of retinoid X receptor (RXR) agonists have proven to be highly effective in preventing methylnitrosourea (MNU) induced mammary cancers. However, these agonists have side effects; particularly causing an increase in serum triglyceride levels. A series of ligands for RXR were designed based on computer modeling to the ligand binding domain (LBD) of the RXR receptors and on structure-activity relationships. The chemopreventive effects of these retinoids were evaluated in the relatively long-term MNU model. As a short-term assay to predict their efficacy, the ability of the retinoids to modulate cell proliferation and apoptosis was also determined in mammary cancers after only 7 days of treatment. The five UAB retinoids evaluated included two Class I UAB retinoids (UAB20, UAB112) and three Class II UAB retinoids (UAB30, 4-methyl-UAB30 and the benzosuberone-analog of UAB30). The previously evaluated RXR agonist targretin and the pan-agonist 9-cis-retinoic acid (9-cis-RA), which interacts with both RAR and RXR receptors, were included as positive agonists known to prevent cancer in the MNU model. In the prevention studies, in which the agents were administered beginning 5 days after MNU until the end of the study, targretin (150 mg/kg diet) and 4-methyl-UAB30 (200 mg/kg diet) were highly effective in decreasing cancer numbers by 75-85%. UAB30 (200 mg/kg diet) and 9-cis-RA (60 mg/kg diet) gave intermediate inhibitions of 60 and 45%, respectively. Targretin (15 mg/kg diet), UAB20 (200 mg/kg diet) and the benzosuberone analog of UAB30 (200 mg/kg diet) showed limited activity by decreasing cancer multiplicity 25-30%, while UAB112 had no effect on mammary cancer multiplicity. A direct correlation was observed between the long-term chemopreventive efficacy of these agents and their ability to decrease cell proliferation in mammary cancers after short-term treatment. Furthermore, the highly effective agents (4-methyl-UAB30 and targretin at 150 mg/kg diet) increased apoptosis 3-5 times, while agents with moderate or limited preventive efficacy failed to significantly increase apoptosis. Although the more effective retinoid treatments increased serum triglycerides 2.5- to 4.0-fold, one moderately effective agent (UAB30) had no significant effect on lipid levels. In summary, a short-term in vivo method has been identified for screening newly synthesized retinoids both for chemopreventive efficacy and for their adverse effect on serum triglycerides.


Atrazine inhibits pulsatile luteinizing hormone release without altering pituitary sensitivity to a gonadotropin-releasing hormone receptor agonist in female Wistar rats.
Atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-tri-azine] is one of the most commonly used herbicides in the United States. Atrazine has been shown to suppress luteinizing hormone (LH) release and can lead to a prolongation of the estrous cycle in the rat. The objectives of this study were to examine the effects of atrazine on normal tonic release of LH and to elucidate the site of action of atrazine in the hypothalamic-pituitary-gonadal axis. Episodic release of gonadotropin-releasing hormone (GnRH) and the corresponding release of LH from the anterior pituitary gland are required for normal reproductive function. To determine if atrazine affects pulsatile LH release, ovariectomized adult female Wistar rats were administered atrazine (50, 100, or 200 mg/kg of body weight daily by gavage) or vehicle control for 4 days. On the final day of atrazine treatment, blood samples were obtained using an indwelling right atrial cannula. In the group receiving 200 mg/kg, there was a significant reduction in LH pulse frequency and a concomitant increase in pulse amplitude. To determine if the effects of atrazine on LH release were due to changes at the level of the pituitary, animals were passively immunized against endogenous GnRH, treated with atrazine, and challenged with a GnRH receptor agonist. Atrazine failed to alter pituitary sensitivity to the GnRH receptor agonist at any dose used. Taken together, these findings demonstrate that high doses of atrazine affect the GnRH pulse generator in the brain and not at the level of gonadotrophs in the pituitary.


Body Composition and Visceral Adipose Tissue in Female Collegiate Equestrian Athletes.
To examine measures of total and regional body composition using dual X-ray absorptiometry (DXA) in NCAA Division I collegiate equestrian athletes, 31 female collegiate equestrian athletes were matched to a population of normal controls by age and body mass index. Total and regional fat tissue mass (FM), lean tissue mass (LM), bone mineral density (BMD), and abdominal visceral adipose tissue (VAT) were measured by DXA. Equestrian athletes had a significantly (p=0.03) lower total body fat percentage (%fat) than controls. There were no significant differences in total LM and VAT between equestrian athletes and controls. However, equestrian athletes, when compared to the controls, had significantly lower leg %fat, leg FM and higher leg LM. The greater leg LM in equestrian riders resulted in a smaller upper to lower body LM ratio compared to controls. There was no difference in leg BMD between equestrian athletes and controls. There were no significant differences between the 2 styles of riding (i. e., hunt seat and western style) in regards to body composition. The lower total %fat in equestrian athletes seems to be influenced by differences in leg composition, with equestrian athletes having significantly more LM and less FM.


Short- to mid-term results of metallic press-fit radial head arthroplasty in unstable injuries of the elbow.
We assessed the short- to mid-term survival of metallic press-fit radial head prostheses in patients with radial head fractures and acute traumatic instability of the elbow. The medical records of 42 patients (16 males, 26 females) with a mean age of 56 years (23 to 85) with acute unstable elbow injuries, including a fracture of the radial head requiring metallic replacement of the radial head, were reviewed retrospectively. Survival of the prosthesis was assessed from the radiographs of 37 patients after a mean follow-up of 50 months (12 to 107). The functional results of 31 patients were assessed using range-of-movement, Mayo elbow performance score (MEPS), Disabilities of the Arm, Shoulder and Hand (DASH) score and the RAND 36-item health survey. At the most recent follow-up 25 prostheses were still well fixed, nine had been removed because of loosening, and three remained implanted but were loose. The mean time from implantation to loosening was 11 months (2 to 24). Radiolucent lines that developed around the prosthesis before removal were mild in three patients, moderate in one and severe in five. Range of movement parameters and mass grip strength were significantly lower in the affected elbow than in the unaffected side. The mean MEPS score was 86 (40 to 100) and the mean DASH score was 23 (0 to 81). According to RAND-36 scores, patients had more pain and lower physical function scores than normal population values. Loosening of press-fit radial head prostheses is common, occurs early, often leads to severe osteolysis of the proximal radius, and commonly requires removal of the prosthesis.


Is residual memory variance a valid method for quantifying cognitive reserve? A longitudinal application.
Cognitive reserve describes the mismatch between brain integrity and cognitive performance. Older adults with high cognitive reserve are more resilient to age-related brain pathology. Traditionally, cognitive reserve is indexed indirectly via static proxy variables (e.g., years of education). More recently, cross-sectional studies have suggested that reserve can be expressed as residual variance in episodic memory performance that remains after accounting for demographic factors and brain pathology (whole brain, hippocampal, and white matter hyperintensity volumes). The present study extends these methods to a longitudinal framework in a community-based cohort of 244 older adults who underwent two comprehensive neuropsychological and structural magnetic resonance imaging sessions over 4.6 years. On average, residual memory variance decreased over time, consistent with the idea that cognitive reserve is depleted over time. Individual differences in change in residual memory variance predicted incident dementia, independent of baseline residual memory variance. Multiple-group latent difference score models revealed tighter coupling between brain and language changes among individuals with decreasing residual memory variance. These results suggest that changes in residual memory variance may capture a dynamic aspect of cognitive reserve and could be a useful way to summarize individual cognitive responses to brain changes. Change in residual memory variance among initially non-demented older adults was a better predictor of incident dementia than residual memory variance measured at one time-point.


Shock attenuation in the human lumbar spine during walking and running.
During locomotion, each step generates a shock wave that travels through the body toward the head. Without mechanisms for attenuation, repeated shocks can lead to pathology. Shock attenuation (SA) in the lower limb has been well studied, but little is known about how posture affects SA in the spine. To test the hypothesis that lumbar lordosis (LL) contributes to SA, 27 adults (14 male, 13 female) walked and ran on a treadmill. Two lightweight, tri-axial accelerometers were affixed to the skin overlying T12/L1 and L5/S1. Sagittal plane accelerations were analyzed using power spectral density analysis, and lumbar SA was assessed within the impact-related frequency range. 3D kinematics quantified dynamic and resting LL. To examine the effects of intervertebral discs on spinal SA, supine MRI scans were used to measure disc morphology. The results showed no association between LL and SA during walking, but LL correlated with SA during running (P<0.01, R2=0.30), resulting in as much as 64% reduction in shock signal power among individuals with the highest LL. Patterns of lumbar spinal motion partially explain differences in SA: larger amplitudes of LL angular displacement and slower angular displacement velocity during running were associated with greater lumbar SA (P=0.008, R2=0.41). Intervertebral discs were associated with greater SA during running (P=0.02, R2=0.22) but, after controlling for disc thickness, LL remained strongly associated with SA (P=0.001, R2=0.44). These findings support the hypothesis that LL plays an important role in attenuating impact shocks transmitted through the human spine during high-impact, dynamic activities such as running.


Serine hydroxymethyltransferase from Escherichia coli: purification and properties.
Serine hydroxymethyltransferase from Escherichia coli was purified to homogeneity. The enzyme was a homodimer of identical subunits with a molecular weight of 95,000. The amino acid sequence of the amino and carboxy-terminal ends and the amino acid composition of cysteine-containing tryptic peptides were in agreement with the primary structure proposed for this enzyme from the structure of the glyA gene (M. Plamann, L. Stauffer, M. Urbanowski, and G. Stauffer, Nucleic Acids Res. 11:2065-2074, 1983). The enzyme contained no disulfide bonds but had one sulfhydryl group on the surface of the protein. Several sulfhydryl reagents reacted with this exposed group and inactivated the enzyme. Spectra of the enzyme in the presence of substrates and substrate analogs showed that the enzyme formed the same complexes and in similar relative concentrations as previously observed with the cytosolic and mitochondrial rabbit liver isoenzymes. Kinetic studies with substrates showed that the affinity and synergistic binding of the amino acid and folate substrates were similar to those obtained with the rabbit liver isoenzymes. The enzyme catalyzed the cleavage of threonine, allothreonine, and 3-phenylserine to glycine and the corresponding aldehyde in the absence of tetrahydrofolate. The enzyme was also inactivated by D-alanine caused by the transamination of the active site pyridoxal phosphate to pyridoxamine phosphate. This substrate specificity was also observed with the rabbit liver isoenzymes. We conclude that the reaction mechanism and the active site structure of E. coli serine hydroxymethyltransferase are very similar to the mechanism and structure of the rabbit liver isoenzymes.


tDCS peripheral nerve stimulation: a neglected mode of action?
Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method widely used by neuroscientists and clinicians for research and therapeutic purposes. tDCS is currently under investigation as a treatment for a range of psychiatric disorders. Despite its popularity, a full understanding of tDCS's underlying neurophysiological mechanisms is still lacking. tDCS creates a weak electric field in the cerebral cortex which is generally assumed to cause the observed effects. Interestingly, as tDCS is applied directly on the skin, localized peripheral nerve endings are exposed to much higher electric field strengths than the underlying cortices. Yet, the potential contribution of peripheral mechanisms in causing tDCS's effects has never been systemically investigated. We hypothesize that tDCS induces arousal and vigilance through peripheral mechanisms. We suggest that this may involve peripherally-evoked activation of the ascending reticular activating system, in which norepinephrine is distributed throughout the brain by the locus coeruleus. Finally, we provide suggestions to improve tDCS experimental design beyond the standard sham control, such as topical anesthetics to block peripheral nerves and active controls to stimulate non-target areas. Broad adoption of these measures in all tDCS experiments could help disambiguate peripheral from true transcranial tDCS mechanisms.


Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma.
Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.


[The work organization of the pharmaceutical department of a hospital for light casualties].
The problem of differential approach in organization of treatment of servicemen who can be returned to their ranks without being evacuated away from Army (Front) zone occupies an important place among the questions of reorganization of the existing medico-evacuation system. This complicated problem cannot be solved without application of effective medications and organization of opportune and adequate supplies with all types of medical equipment. The experience of tactico-special exercises has shown that task could be solved successfully by pharmaceutical section of a hospital for minimally wounded. The organic structure of this section is the following: chief of the section, pharmacist, chemist, medical assistant and practical nurse-washer. Besides standard pharmaceutical facilities new equipment and devices based on up-to-date technologies were used during the exercises.


Anisotropy of the magnetoresistance in Gd5Si2Ge2.
The observed magnetoresistance of single crystalline Gd5Si2Ge2 is negative and strongly anisotropic. The absolute values measured along the [100] and [010] directions exceed those parallel to the [001] direction by more than 60%. First principles calculations demonstrate that a structural modification is responsible for the anisotropy of the magnetoresistance, and that the latter is due to a significant reduction of electronic velocity in the [100] direction and the anisotropy of electrical conductivity.


Treatment of acute corneal hydrops with intracameral C3F8 in a patient of pellucid marginal degeneration with keratoglobus.
We report the use of perfluoropropane (C(3)F(8)) gas for the treatment of acute hydrops with intrastromal cleft in a case of pellucid marginal degeneration with keratoglobus. Acute hydrops in a 36-year-old man with pellucid marginal degeneration with keratoglobus was treated with intracameral injection of 0.3 mL isoexpansile C(3)F(8) (14%). Reduction in corneal haze was seen beginning from the third postoperative day. Significant clearing had taken place by the end of the second week with the closure of intrastromal cleft. Best corrected visual acuity improved from finger counting at 1 foot preoperatively to 6/18 after 2 weeks. There was no postoperative rise in intraocular pressure or cataract formation. Intracameral injection of C(3)F(8) may possibly be a viable treatment option for acute hydrops in a case of corneal ectasia. Larger studies are required to clarify the role of intracameral gas injection in the treatment of acute hydrops in corneal ectasia.


Towards Biohybrid Lung Development-Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization.
To provide an alternative treatment option for patients with end-stage lung disease, we aim for biohybrid lung development (BHL) based on hollow fiber membrane (HFM) technology used in extracorporeal membrane oxygenators. For long-term BHL application, complete hemocompatibility of all blood-contacting surfaces is indispensable and can be achieved by their endothelialization. Indeed, albumin/heparin (AH) coated HFM enables initial endothelialization, but as inexplicable cell loss under flow conditions was seen, we assessed an alternative HFM coating using fibronectin (FN). Therefore, endothelial cell (EC) adherence and viability on both coated HFM were analyzed by fluorescence-based staining. Functional leukocyte and thrombocyte adhesion assays were performed to evaluate hemocompatibility, also in comparison to blood plasma coated HFM as a clinically relevant control. To assess monolayer resistance and EC behavior under clinically relevant flow conditions, a mock circulation setup was established, which also facilitates imitation of lung-disease specific blood gas settings. Besides quantification of flow-associated cell loss, endothelial responses towards external stimuli, like flow exposure or TNFα stimulation, were analyzed by qRT-PCR, focusing on inflammation, thrombus formation and extracellular matrix production. Under static conditions, both coated HFM enabled the generation of a viable, confluent, non-inflammatory and anti-thrombogenic monolayer. However, by means of homogenous FN coating, cell retention and physiologic gene regulation towards an improved hemocompatible-and extracellular matrix producing phenotype, was significantly superior compared to the inhomogeneous AH coating. In summary, our adaptable in-house FN coating secures the endothelial requirements for long-term BHL application and may promote monolayer establishment on all other blood contacting surfaces of the BHL (e.g., cannulae).


Papillary thyroid carcinoma: bilateral choroidal metastases with extrascleral extension.
Here, we present the case of a patient with bilateral choroidal metastases with extraocular extension in one eye. Metastasis of papillary thyroid carcinoma to the uvea is extremely rare, with only 6 patients reported in the literature. A 62-year-old man with a prior history of papillary thyroid carcinoma suffered the rapid loss of vision in his right eye. He had neovascular glaucoma, total retinal detachment, and a solitary choroidal mass. A month later, his left visual acuity also decreased because of a small macular choroidal mass. The right eye was enucleated and a nodular lesion over the sclera representing extraocular extension was observed. This tumor and the intraocular lesion were composed of papillary excrescences and cystic spaces and stained positively for thyroid transcription factor 1 and thyroglobulin, all confirming the diagnosis of metastatic papillary thyroid carcinoma. The tumor in the left eye was successfully treated with diode laser transpupillary thermotherapy. The patient expired within a month as a result of widespread pulmonary metastases. Papillary thyroid carcinoma may metastasize to the uvea bilaterally, cause rapid visual function loss, erode the sclera, and may extend outside the globe similar to choroidal melanoma. This aggressive ocular involvement was associated with a dismal prognosis in our patient.


Transforming growth factor-beta and forskolin increase all classes of insulin-like growth factor-I transcripts in normal human osteoblast-like cells.
In this study, we examined regulation of insulin-like growth factor I (IGF-I) gene expression and transcript splicing in normal human osteoblast-like cells. Previous studies in rat osteoblastic cells have indicated that transforming growth factor-beta (TGF-beta) inhibits IGF-I expression, whereas inducers of intracellular cAMP stimulate IGF-I expression. However, in human osteoblast-like cells both TGF-beta and forskolin increased IGF-I mRNA levels in a time- and dose-dependent manner. All 4 classes of IGF-I transcript that can result from alternate leader exon usage and splicing of the human IGF-I gene were induced proportionally. Although human osteoblasts increase IGF-I mRNA in response to important skeletal regulatory factors, some responses may be species-specific.


[Relationship of socioeconomic factors with medical utilization for lower urinary tract symptoms and benign prostatic hyperplasia in a South Korean community].
We wanted to evaluate the medical underutilization for benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) among Korean elderly men and we wanted to determine their associated factors. This study was conducted on 239 men with LUTS and 116 men with BPH who were compatible with the diagnostic criteria from a total of 641 participants. These participants were over 50 years old and they were randomly chosen in a community-based study for estimating the prevalence of BPH. Using a self-reported questionnaire, we surveyed the sociodemographics, health status, quality of life, lower urinary tract symptoms, medical utilization and reasons for not seeking treatment. Only 27.6% of the men with LUTS and 31.0% of the men with BPH reported having visited a doctor for urinary symptoms. The reasons for not visiting a doctor were, in order of responses from the group with LUTS: 'considered the symptoms as a part of the normal ageing process', 'not enough time to visit a doctor', 'financial difficulty' and 'the symptoms were not severe or bothersome'. Regarding BPH, the responses were the same as those of the group with LUTS however, 'financial difficulty' placed second. Among the men with experience of visiting a doctor for urinary symptoms, 33.3% of those with LUTS and 28.1% of those with BPH were not treated. The most common reason in both groups was 'the symptoms were not severe to be treated'. On a multiple logistic regression analysis, the larger size household (odds ratio (OR) 3.03, 95% confidence interval (Cl) = 1.40-6.54) and an unsatisfactory quality of life related with urinary symptoms (OR 2.98, 95% CI = 1.23-7.21) were associated with medical utilization in the group of LUTS. For BPH, the current employment status was related with the medical utilization (OR 2.80, 95% CI = 1.10-7.11), in addition to the larger size household (OR 3.24, 95% CI = 1.14-9.21). Many men with urinary symptoms do not visit a doctor. This medical underutilization for people with LUTS and BPH may be associated with economic status in Korea.


Creating a collaborative environment to care for complex patients and families.
Today's critical care environment is increasingly complex due to technological advancements, greater intensity of interventions, and a myriad of healthcare providers. Critically ill patients and their families can feel overwhelmed with the stress of the environment in addition to the acute illness. This stress affects the patients' and families' ability to function, cope, and understand complex information. For some families, this experience precipitates distrustful relationships with care providers. The resulting impact on quality of care, staff morale, length of stay, and cost is high. The purpose of this article is to describe issues encountered by one medical center in caring for complex patients and families. A representative case outlines the types of issues the staff in the adult intensive care units faced. Use of a comprehensive problem-solving model to address concerns resulted in structured approaches to guide healthcare providers in caring for complex patients and families. The goal of these approaches was to support all parties involved in the care of complex patients, improve communication, and avoid crises that resulted from distrustful relationships and lack of skill in resolving conflict.


Final Long-Term Reporting from a Randomized Controlled IDE Trial for Lumbar Artificial Discs in Single-Level Degenerative Disc Disease: 7-Year Results.
This study compared 7-year safety and efficacy outcomes of activL and ProDisc-L lumbar total disc replacements in patients with symptomatic, single-level lumbar degenerative disc disease (DDD). The objectives are to report 7-year outcomes of the trial, evaluate the outcomes for patients lost to follow-up, and determine whether early outcomes predict long-term outcomes. This was a prospective, multicenter, randomized, controlled investigational device exemption study. Eligible patients with symptomatic, single-level lumbar DDD had failed ≥6 months of nonsurgical management. Patients (N = 283) were randomized to receive activL (n = 218) or ProDisc-L (n = 65). At 7 years, data were available from 206 patients (activL, 160; ProDisc-L, 46). Logistic regression models were fit to predict 7-year outcomes for patients lost to follow-up after 2 years. At 7 years, the activL group was noninferior to the ProDisc-L group on the primary composite endpoint (P = .0369). Both groups showed significant reductions in back/leg pain severity and improvements in disability index and quality-of-life relative to baseline (P < .0001). In both groups, opioid use was significantly reduced at 7 years (0%) relative to baseline (P < .01), and the overall reoperation rates were low (4.6%). activL patients showed a significantly better range of motion (ROM) for flexion-extension rotation than ProDisc-L patients (P = .0334). A significantly higher proportion of activL patients did not report serious adverse events (activL, 62%; ProDisc-L, 43%; P = .011). Predictive modeling indicated that >70% of patients (depending on outcome) lost to follow-up after 2 years would show clinically significant improvement at 7 years if improvements were achieved at 2 years. The benefits of activL and ProDisc-L are maintained after 7 years, with significant improvements from baseline observed in pain, function, and opioid use. activL is more effective at preserving ROM than ProDisc-L and has a more favorable safety profile. Improvements in other primary and secondary outcomes were similar between both disc designs. 1.


[Detection mutations in the DNA mismatch repair genes of hMLH1 and hMSH2 genes in Colombian families with suspicion of hereditary non-polyposis colorectal carcinoma (Lynch syndrome)].
Colorectal cancer (CRC) is the second highest cause of cancer mortality in developed countries. In Colombia, CRC ranks fifth as a cause of cancer death. Approximately 75% of CRC appear to be spontaneous and 25% are familial, with 5% of the latter clearly hereditary. Of these, hereditary non-polyposis colorectal carcinoma (HNPCC)-or Lynch syndrome is the most important. Herein, the two most important genes involved in Lynch syndrome, the hMLH1 and hMSH2 were analyzed for presence of mutations. Seventeen Colombian families that fulfilled the Amsterdam II criteria or Bethesda guidelines for Lynch syndrome were selected. The of 35 exons of hMLH1 and hMSH2 genes were screened by SSCP and those with electrophoretic variants were sequenced. Eight germinal mutations were detected, corresponding to a 47% detection mutation rate. Six of the eight mutations have previously been reported. These consisted of the following mutations: a single base substitution at the donor splicing site of exon 9, a single base substitution (A>G) at codon 755 of the exon 17, and another single base substitution (G>A) at codon 681 of exon 18. The two novel mutations consisted of a single base substitution (C>T) at codon 640 of exon 17 of the hMLH1 gene and a two-nucleotide deletion (TG) at codon 184 of exon 3 of hMSH2 gene. In addition, two families were observed with a polymorphism in the intron 13 (G>A) nt 1558+14, of hMLH1 gene. This study represented the first survey for detecting mutations associated with Lynch syndrome in Colombia, and is intended to lead to the establishment of a management and prevention program.


Major hepatic resection in a residency training program.
Records of 30 major hepatic resections performed at David Grant USAF Medical Center and Wilford Hall USAF Medical Center were analyzed to assess the feasibility, safety, and resources required for such procedures in a general surgery residency training program. The mean intraoperative blood loss during surgery was 2022 mL and the mean intraoperative transfusion volume was 4.2 units of packed red blood cells. Patients spent an average of 2.7 days in the intensive care unit, with a mean overall postoperative stay of 15 days. One death occurred within 30 days of operation due to a postoperative myocardial infarction, and another death during the hospital stay was due to hepatic insufficiency and Candida endocarditis. Overall, five major postoperative complications occurred (17%), one requiring reoperation. All but one procedure was done by a closely supervised surgical resident. This experience compares favorably with others in the literature and supports the practice of hepatic resection as part of surgical training.


Examining the interplay between face mask usage, asymptomatic transmission, and social distancing on the spread of COVID-19.
COVID-19's high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-based model within a closed space that approximated real-life interactions. By explicitly considering different fractions of asymptomatic individuals, as well as a realistic hypothesis of face masks protection during inhaling and exhaling, our simulations demonstrate that a synergistic use of face masks and social distancing is the most effective intervention to curb the infection spread. To control the pandemic, our models suggest that high adherence to social distance is necessary to curb the spread of the disease, and that wearing face masks provides optimal protection even if only a small portion of the population comply with social distance. Finally, the face mask effectiveness in curbing the viral spread is not reduced if a large fraction of population is asymptomatic. Our findings have important implications for policies that dictate the reopening of social gatherings.


Scheduling Anesthesia Time Reduces Case Cancellations and Improves Operating Room Workflow in a University Hospital Setting.
A new method of scheduling anesthesia-controlled time (ACT) was implemented on July 1, 2012 in an academic inpatient operating room (OR) department. This study examined the relationship between this new scheduling method and OR performance. The new method comprised the development of predetermined time frames per anesthetic technique based on historical data of the actual time needed for anesthesia induction and emergence. Seven "anesthesia scheduling packages" (0 to 6) were established. Several options based on the quantity of anesthesia monitoring and the complexity of the patient were differentiated in time within each package. This was a quasi-experimental time-series design. Relevant data were divided into 4 equal periods of time. These time periods were compared with ANOVA with contrast analysis: an intervention, pre-intervention, and post-intervention contrast were tested. All emergency cases were excluded. A total of 34,976 inpatient elective cases performed from January 1, 2010 to December 31, 2014 were included for statistical analyses. The intervention contrast showed a significant decrease (p < 0.001) of 4.5% in the prediction error. The total number of cancellations decreased to 19.9%. The ANOVA with contrast analyses showed no significant differences with respect to under- and over-used OR time and raw use. Unanticipated results derived from this study, allowing for a smoother workflow: eg anesthesia nurses know exactly which medical equipment and devices need to be assembled and tested beforehand, based on the scheduled anesthesia package. Scheduling the 2 major components of a procedure (anesthesia- and surgeon-controlled time) more accurately leads to fewer case cancellations, lower prediction errors, and smoother OR workflow in a university hospital setting.


ErbB3 (HER3) interaction with the p85 regulatory subunit of phosphoinositide 3-kinase.
ErbB3 (HER3), a unique member of the ErbB receptor family, lacks intrinsic protein tyrosine kinase activity and contains six Tyr-Xaa-Xaa-Met (YXXM) consensus binding sites for the SH2 domains of the p85 regulatory subunit of phosphoinositide 3-kinase. ErbB3 also has a proline-rich sequence that forms a consensus binding site for the SH3 domain of p85. Here we have investigated the interacting domains of ErbB3 and p85 by a unique application of the yeast two-hybrid system. A chimaeric ErbB3 molecule containing the epidermal growth factor receptor protein tyrosine kinase domain was developed so that the C-terminal domain of ErbB3 could become phosphorylated in the yeast system. We also generated several ErbB3 deletion and Tyr-->Phe site-specific mutants, and observed that a single ErbB3 YXXM motif was necessary and sufficient for the association of ErbB3 with p85. The incorporation of multiple YXXM motifs into the ErbB3 C-terminus enabled a stronger ErbB3/p85 interaction. The proline-rich region of ErbB3 was not necessary for interaction with p85. However, either deletion or mutation of the p85 SH3 domain decreased the observed ErbB3/p85 association. Additionally an ErbB3/p85 SH3 domain interaction was detected by an assay in vitro. These results were consistent with a model in which pairs of phosphorylated ErbB3 YXXM motifs co-operate in binding to the tandem SH2 domains of p85. Although a contributing role for the p85 SH3 domain was suggested, the N- and C-terminal SH2 domains seemed to be primarily responsible for the high-affinity association of p85 and ErbB3.


Preclinical evaluation of "whole" cell vaccines for prophylaxis and therapy using a disabled infectious single cycle-herpes simplex virus vector to transduce cytokine genes.
The development of genetically modified "whole" tumor cell vaccines for cancer therapy relies on the efficient transduction and expression of genes by vectors. In the present study, we have used a disabled infectious single cycle-herpes simplex virus 2 (DISC-HSV-2) vector constructed to express cytokine or marker genes upon infection. DISC-HSV-2 is able to infect a wide range of tumor cells and efficiently express the beta-galactosidase reporter gene, granulocyte-macrophage colony-stimulating factor (GM-CSF), or IL-2 genes. Gene expression occurred rapidly after infection of tumor cells, and the level of production of the gene product (beta-galactosidase, GM-CSF, or IL-2) was shown to be both time-and dose-dependent. Vaccination with irradiated DISC-mGM-CSF or DISC-hIL-2-infected murine tumor cells resulted in greatly enhanced immunity to tumor challenge with live parental tumor cells compared with control vaccines. When used therapeutically to treat existing tumors, vaccination with irradiated DISC-mGM-CSF-infected tumor cells significantly reduced the incidence and growth rates of tumors when administered locally adjacent to the tumor site, providing up to 90% protection. The prophylactic and therapeutic efficacy of DISC-mGM-CSF-infected cells was shown initially using a murine renal cell carcinoma model (RENCA), and the results were confirmed in two additional murine tumor models: the M3 melanoma and 302R sarcoma. Therapy with DISC-infected RENCA "whole" cell vaccines failed to reduce the incidence or growth of tumor in congenitally T-cell deficient (Nu+/Nu+) mice or mice depleted of CD4+ and/or CD8+ T-lymphocytes, confirming that both T-helper and T-cytotoxic effector arms of the immune response are required to promote tumor rejection. These preclinical results suggest that this "novel" DISC-HSV vector may prove to be efficacious in developing genetically modified whole-cell vaccines for clinical use.


[Study in oral cavity alterations in patients with gastroesophageal reflux disease].
The gastroesophageal reflux disease, which has become highly and increasingly incident, may be manifested by typical (pyrosis and regurgitation) and atypical (pulmonary, otorhinolaryngological and buccal) symptoms. To analyze alterations in the oral cavity patients with gastroesophageal reflux disease. One hundred patients were studied being 50 gastroesophageal reflux disease patients (group 1) and 50 controls (group 2). All patients were submitted to an oral clinical exam and specific survey. Patients in group 1 were submitted to upper endoscopy, manometry and esophageal pH monitoring. The upper endoscopy revealed esophagitis in all patients, 20 erosive esophagitis, 30 no-erosive esophagitis and 38 hiatal hernia. Average pressure of the lower esophageal sphincter was 11 +/- 4,8 mm Hg and of the upper esophageal sphincter 75 +/- 26,5 mm Hg. In 42 patients of group 1 (84%) pathological gastroesophageal reflux was observed. Clinical exams revealed: dental erosions in group 1: 273 faces and in group 2: 5 tooth decays in group 1: 23 and 115 in group 2; abrasion in group 1: 58 and in group 2: 95; attrition wear: 408 in group 1 and 224 in group 2. The most damages was the palatine face. In group 1, 21 patients complained about frequent episodes of canker sores, 35 of tooth sensibility, 26 of burning mouth and 42 of sour taste in the mouth. In group 2 the complaints were observed in lower number of patients. Patients with gastroesophageal reflux disease present higher incidence of dental erosion, canker sores, mouth burning sensation, sensitivity and sour taste than controls. Patients with gastroesophageal reflux disease show lower incidence of tooth decays as compared to controls.


A genomic overview of the population structure of Salmonella.
For many decades, Salmonella enterica has been subdivided by serological properties into serovars or further subdivided for epidemiological tracing by a variety of diagnostic tests with higher resolution. Recently, it has been proposed that so-called eBurst groups (eBGs) based on the alleles of seven housekeeping genes (legacy multilocus sequence typing [MLST]) corresponded to natural populations and could replace serotyping. However, this approach lacks the resolution needed for epidemiological tracing and the existence of natural populations had not been independently validated by independent criteria. Here, we describe EnteroBase, a web-based platform that assembles draft genomes from Illumina short reads in the public domain or that are uploaded by users. EnteroBase implements legacy MLST as well as ribosomal gene MLST (rMLST), core genome MLST (cgMLST), and whole genome MLST (wgMLST) and currently contains over 100,000 assembled genomes from Salmonella. It also provides graphical tools for visual interrogation of these genotypes and those based on core single nucleotide polymorphisms (SNPs). eBGs based on legacy MLST are largely consistent with eBGs based on rMLST, thus demonstrating that these correspond to natural populations. rMLST also facilitated the selection of representative genotypes for SNP analyses of the entire breadth of diversity within Salmonella. In contrast, cgMLST provides the resolution needed for epidemiological investigations. These observations show that genomic genotyping, with the assistance of EnteroBase, can be applied at all levels of diversity within the Salmonella genus.


Machine Learning Uncovers Food- and Excipient-Drug Interactions.
Inactive ingredients and generally recognized as safe compounds are regarded by the US Food and Drug Administration (FDA) as benign for human consumption within specified dose ranges, but a growing body of research has revealed that many inactive ingredients might have unknown biological effects at these concentrations and might alter treatment outcomes. To speed up such discoveries, we apply state-of-the-art machine learning to delineate currently unknown biological effects of inactive ingredients-focusing on P-glycoprotein (P-gp) and uridine diphosphate-glucuronosyltransferase-2B7 (UGT2B7), two proteins that impact the pharmacokinetics of approximately 20% of FDA-approved drugs. Our platform identifies vitamin A palmitate and abietic acid as inhibitors of P-gp and UGT2B7, respectively; in silico, in vitro, ex vivo, and in vivo validations support these interactions. Our predictive framework can elucidate biological effects of commonly consumed chemical matter with implications on food- and excipient-drug interactions and functional drug formulation development.


Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with Parkinson's Disease.
Parkinson's disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions.


Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population.
The purpose of the present study was to investigate the possible association of paraoxonase-1 (PON1) 192/55 polymorphisms with lung cancer (LC) risk in a Turkish population. A population-based, case-control study was carried out, including 223 patients with LC and 234 controls. The frequencies of PON1 192/55 genotypes were compared in patient and control groups using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Distribution of PON1 192 R (+) genotype was found to be significantly higher in patients with LC compared to the controls (odds ratio: 1.497, 95% confidence interval: 1.034-2.166). This difference was especially noteworthy in patients with small cell carcinoma and squamous cell carcinoma. This is the first case-control study on the association between PON1 polymorphisms and LC susceptibility in a Turkish population. Our results suggest that PON1 192 polymorphsim is associated with an increased risk of LC in the Turkish population and may be a useful genetic marker for small cell and squamous cell carcinoma.


Development and functioning of the mobile app-based mh-GAP intervention guide in detection and treatment of people with mental health conditions in primary healthcare settings in Nepal.
This paper describes the development process of a mobile app-based version of the World Health Organization mental health Gap Action Programme Intervention Guide, testing of the app prototypes, and its functionality in the assessment and management of people with mental health conditions in Nepal. Health workers' perception of feasibility and acceptability of using mobile technology in mental health care was assessed during the inspiration phase (N = 43); the ideation phase involved the creation of prototypes; and prototype testing was conducted over multiple rounds with 15 healthcare providers. The app provides provisional diagnoses and treatment options based on reported symptoms. Participants found the app prototype useful in reminding them of the process of assessment and management of mental disorders. Some challenges were noted, these included a slow app prototype with multiple technical problems, including difficulty in navigating 'yes'/'no' options, and there were challenges reviewing detailed symptoms of a particular disorder using a "more information" icon. The initial feasibility work suggests that if the technical issues are addressed, the e-mhGAP warrants further research to understand if it is a useful method in improving the detection of people with mental health conditions and initiation of evidence-based treatment in primary healthcare facilities.


Microtubule-associated proteins 1 (MAP1) promote human immunodeficiency virus type I (HIV-1) intracytoplasmic routing to the nucleus.
After cell entry, HIV undergoes rapid transport toward the nucleus using microtubules and microfilaments. Neither the cellular cytoplasmic components nor the viral proteins that interact to mediate transport have yet been identified. Using a yeast two-hybrid screen, we identified four cytoskeletal components as putative interaction partners for HIV-1 p24 capsid protein: MAP1A, MAP1S, CKAP1, and WIRE. Depletion of MAP1A/MAP1S in indicator cell lines and primary human macrophages led to a profound reduction in HIV-1 infectivity as a result of impaired retrograde trafficking, demonstrated by a characteristic accumulation of capsids away from the nuclear membrane, and an overall defect in nuclear import. MAP1A/MAP1S did not impact microtubule network integrity or cell morphology but contributed to microtubule stabilization, which was shown previously to facilitate infection. In addition, we found that MAP1 proteins interact with HIV-1 cores both in vitro and in infected cells and that interaction involves MAP1 light chain LC2. Depletion of MAP1 proteins reduced the association of HIV-1 capsids with both dynamic and stable microtubules, suggesting that MAP1 proteins help tether incoming viral capsids to the microtubular network, thus promoting cytoplasmic trafficking. This work shows for the first time that following entry into target cells, HIV-1 interacts with the cytoskeleton via its p24 capsid protein. Moreover, our results support a role for MAP1 proteins in promoting efficient retrograde trafficking of HIV-1 by stimulating the formation of stable microtubules and mediating the association of HIV-1 cores with microtubules.


A Teenager With Acute Anterograde Amnesia.
Isolated amnesia is an uncommon presenting complaint in the pediatric age group. We report the case of an 18-year-old woman who presented with the acute onset of memory difficulty and an otherwise normal neurologic examination. Brain magnetic resonance imaging demonstrated inflammation in the bilateral temporal lobes. Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of autoimmune encephalitis. Although rare, the acute onset of isolated amnesia deserves a prompt, comprehensive evaluation.


Rational one-step synthesis of porous PtPdRu nanodendrites for ethanol oxidation reaction with a superior tolerance for CO-poisoning.
Precise fabrication of porous ternary Pt-based nanodendrites is very important for electrochemical energy conversion owing to high surface area and great molecular accessibility of these nanodendrites. Herein, PtPdRu porous nanodendrites (PNDs) were prepared via a facile one-step ultrasonic irradiation approach at room temperature. Intriguingly, the ultrasonic irradiation drove the formation of PtPdRu PNDs with spatially interconnected porous structures, whereas magnetic stirring produced PtPdRu nanoflowers (NFs) with less porosity. The formation mechanism was ascribed to the acoustic cavitation effect and fast-reduction kinetics under sonication. The as-made PtPdRu PNDs displayed a superior catalytic performance towards ethanol oxidation reaction with a high tolerance for CO-poisoning as compared to PtPdRu NFs, PtPd NDs, and commercial Pt/C catalyst.


The Endocannabinoid System Affects Myocardial Glucose Metabolism in the DOCA-Salt Model of Hypertension.
Recent interest in the use of cannabinoids as therapeutic agents has revealed the involvement of the endogenous cannabinoid system (ECS) in the regulation of the cardiovascular system in hypertension. Abnormalities in glucose metabolism and insulin action are commonly detected in hypertensive animals. Thus, potential antihypertensive drugs should be investigated with respect to modulation of glucose homeostasis. Therefore, the aim of the present study was to evaluate the effects of the ECS activation after chronic fatty acid amide hydrolase inhibitor (URB597) administration on plasma glucose and insulin concentrations as well as parameters of myocardial glucose metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rats, an animal model of secondary hypertension. Hypertension was induced by DOCA (25mg/kg) injections and addition of 1% NaCl in the drinking water for six weeks. Chronic activation of the ECS was performed by URB597 (1mg/kg) injections for two weeks. We examined fasting plasma levels of insulin (ELISA), glucose and intramyocardial glycogen (colorimetric method). Expressions of glucose transporters (GLUT1, 4) and selected proteins engaged in GLUT translocation as well as glucose metabolism were determined using Western blotting. Hypertension induced hypoinsulinemia with concomitant lack of significant changes in glycemia, reduced intramyocardial glycogen content and increased pyruvate dehydrogenase (PDH) expression in the cardiac muscle. Importantly, chronic URB597 administration in the hypertensive rats increased insulin concentration, elevated plasmalemmal GLUT1 and GLUT4 expression and concomitantly improved myocardial glycogen storage. Chronic administration of fatty acid amide hydrolase (FAAH) inhibitor has potential protective properties on myocardial glucose metabolism in hypertension.


Four candles. Original perspectives and insights into 18th century hospital child healthcare.
It has only recently been recognised that for more than a century before the opening of Great Ormond Street Hospital for Children (1852) children were treated and even admitted in English Voluntary Hospitals. Among the earliest English 18th century records, that contain the patient's age, are those found at the Northampton General Hospital within an archive dating from its foundation as the Northampton Infirmary in 1744. They afford a fascinating glimpse into both inpatient and outpatient child health. Although there are no medical notes as such, the hospital archive has recently rediscovered 1743 statutes, contemporary patient literature entitled Some Friendly Advice to a Patient (written by the Northampton Infirmary's founding physician Dr (later Sir) James Stonhouse), minute books, contemporary engravings of the outside and inside of the hospital and inpatient menus. Thus we can speculate with a high degree of certainty as to what would be the then current infirmary environment and treatments for illustrative examples of the children seen in the period 1744-45 (two inpatients and two outpatients). Interestingly one of the inpatient cases, Elizabeth Ager, a child with fever, was admitted against the infirmary regulations, suggesting already a stretching of boundaries in favour of paediatric admissions. This paper gives a flavour of 18th century hospital child healthcare in an era before the formal recognition of paediatrics as a medical specialty and preceding by more than a century the construction of specialist provision through the foundation of the first children's hospitals.


The Investigation of Lipoxygenases as Therapeutic Targets in Malignant Pleural Mesothelioma.
Advanced malignant pleural mesothelioma (MPM) has an extremely poor prognosis with limited chemotherapy options, therefore the identification of new therapeutic targets would aid in disease management. Arachidonic acid is metabolised by cyclooxygenase and lipoxygenase enzymes. The lipoxygenase isoenzymes 5-LOX and 12-LOX have been implicated in carcinogenesis. We aimed to examine 5-LOX and 12-LOX protein expression in a large retrospective series of mesothelioma samples. Further to this, the in vitro cytotoxic effects of lipoxygenase pathway inhibitors were investigated in mesothelioma cells. Archival samples from 83 patients with MPM were examined by immunohistochemistry for expression of the 5-LOX and 12-LOX proteins. The MTS assay was used to assess cell viability following 72 h treatment with the lipoxygenase pathway inhibitors baicalein, licofelone, MK-886 and zileuton in the MPM cell lines NCI-H2052, NCI-H2452 and MSTO-211H. Positive 12-LOX protein expression was recorded in 69/83 (83%) and positive 5-LOX expression was observed in 56/77 (73%) of MPM tissue samples. Co-expression of 5-LOX with 12-LOX was seen in 46/78 (58%) of MPM samples. Positive expression of 5-LOX, 12-LOX and COX-2 proteins was identified in the NCI-H2052, NCI-H2452 and MSTO-211H MPM cell lines. Baicalein (12-LOX and 15-LOX inhibitor) was effective in 3/3 MPM cell lines at low concentrations with an IC50 range of 9.6 μM to 20.7 μM. We have demonstrated that the 5-LOX and 12-LOX proteins are expressed in a significant proportion of MPM samples (73% and 83% respectively) and may represent novel therapeutic targets in this disease. We have demonstrated that the inhibition of the LOX pathway using baicalein may be effective as a novel treatment for MPM, however further human pharmacokinetic studies are required in order to establish whether the concentration used in vitro is clinically achievable.


Purification and partial characterization of cytosolic malate dehydrogenase from Tritrichomonas foetus.
A cytosolic malate dehydrogenase from Tritrichomonas foetus (Riedmüller) was purified to apparent homogeneity by a combination of differential centrifugation, affinity, hydrophobic interaction and ion-exchange chromatography. The purest preparation had specific activity of 309 mumoles.(mg protein)-1.min-1, which corresponded to 50-fold purification. The enzyme representing almost 2% of total cytosolic protein displayed hyperbolic affinity curves for substrate and coenzyme. Km for oxaloacetate and NADH was 17.5 microM and 13 microM, respectively. Subunit size determined by SDS-PAGE and by laser desorption mass spectroscopy was approximately 37 kDa, which corresponds to values reported for most malate dehydrogenases. The native molecular weight determined by gel filtration was 244 kDa, indicating six subunit structure of holoenzyme; this is unusual in comparison with other malate dehydrogenases, which are usually dimers or tetramers.


Inter-Cohort Validation of SuStaIn Model for Alzheimer's Disease.
Alzheimer's disease (AD) is a neurodegenerative disorder which spans several years from preclinical manifestations to dementia. In recent years, interest in the application of machine learning (ML) algorithms to personalized medicine has grown considerably, and a major challenge that such models face is the transferability from the research settings to clinical practice. The objective of this work was to demonstrate the transferability of the Subtype and Stage Inference (SuStaIn) model from well-characterized research data set, employed as training set, to independent less-structured and heterogeneous test sets representative of the clinical setting. The training set was composed of MRI data of 1043 subjects from the Alzheimer's disease Neuroimaging Initiative (ADNI), and the test set was composed of data from 767 subjects from OASIS, Pharma-Cog, and ViTA clinical datasets. Both sets included subjects covering the entire spectrum of AD, and for both sets volumes of relevant brain regions were derived from T1-3D MRI scans processed with Freesurfer v5.3 cross-sectional stream. In order to assess the predictive value of the model, subpopulations of subjects with stable mild cognitive impairment (MCI) and MCIs that progressed to AD dementia (pMCI) were identified in both sets. SuStaIn identified three disease subtypes, of which the most prevalent corresponded to the typical atrophy pattern of AD. The other SuStaIn subtypes exhibited similarities with the previously defined hippocampal sparing and limbic predominant atrophy patterns of AD. Subject subtyping proved to be consistent in time for all cohorts and the staging provided by the model was correlated with cognitive performance. Classification of subjects on the basis of a combination of SuStaIn subtype and stage, mini mental state examination and amyloid-β1-42 cerebrospinal fluid concentration was proven to predict conversion from MCI to AD dementia on par with other novel statistical algorithms, with ROC curves that were not statistically different for the training and test sets and with area under curve respectively equal to 0.77 and 0.76. This study proves the transferability of a SuStaIn model for AD from research data to less-structured clinical cohorts, and indicates transferability to the clinical setting.


Food poisoning caused by parahaemolytic and NAG vibrios after eating meat products.
At total of 15 subjects taken ill with food poisoining caused by parahaemolytic and NAG vibrios after eating boiled pork sausage and boiled veal stomach were examined. The meat products were secondarily contamined in the sausage factory due to the use od non-disinfected lake water which was found to be a natural medium of the vibrios. When the use of this water was prohibited, the contamination of the factory and the meat products disappeared and no further cases of food poisoning due to meat products were notified. The disease has a toxic character, runs a bening course and end after 2--3 days by restoration to full health.


Changing human visual field organization from early visual to extra-occipital cortex.
The early visual areas have a clear topographic organization, such that adjacent parts of the cortical surface represent distinct yet adjacent parts of the contralateral visual field. We examined whether cortical regions outside occipital cortex show a similar organization. The BOLD responses to discrete visual field locations that varied in both polar angle and eccentricity were measured using two different tasks. As described previously, numerous occipital regions are both selective for the contralateral visual field and show topographic organization within that field. Extra-occipital regions are also selective for the contralateral visual field, but possess little (or no) topographic organization. A regional analysis demonstrates that this weak topography is not due to increased receptive field size in extra-occipital areas. A number of extra-occipital areas are identified that are sensitive to visual field location. Neurons in these areas corresponding to different locations in the contralateral visual field do not demonstrate any regular or robust topographic organization, but appear instead to be intermixed on the cortical surface. This suggests a shift from processing that is predominately local in visual space, in occipital areas, to global, in extra-occipital areas. Global processing fits with a role for these extra-occipital areas in selecting a spatial locus for attention and/or eye-movements.


Roadsides provide refuge for orchids: characteristic of the surrounding landscape.
Seminatural habitats are declining throughout the world; thus, the role of small anthropogenic habitats in the preservation of plants is becoming increasingly appreciated. Here, we surveyed the orchid flora of roadside verges in five Central European countries (Austria, Hungary, Romania, Slovakia, and Slovenia) and tested how the surrounding landscape matrix affects the overall number of species and individuals, and also different functional groups of orchids. We found more than 2,000 individuals of 27 orchid species during our surveys. According to our results, the increasing coverage of agricultural and urban areas negatively affects both the number of orchid species and individuals on roadsides. Our study further suggests that differences in the surrounding habitats affect which species are found on roadsides, since the increasing coverage of grasslands or forested areas around orchid occurrences had a significant positive effect on the number of grassland or forest-dwelling species and individuals, respectively. Most variance in orchid numerosity and diversity was explained by the cover of the suitable habitat types of the respective taxa in the surrounding landscape of the sampling points. This highlights the importance of roadsides acting as refugia for numerous species and valuable plant communities as well as in supporting biodiversity in general.


Disparities in evaluation at certified primary stroke centers: reasons for geographic and racial differences in stroke.
Evaluation at primary stroke centers (PSCs) has the potential to improve outcomes for patients with stroke. We looked for differences in evaluation at Joint Commission certified PSCs by race, education, income, and geography (urban versus nonurban; Southeastern Stroke Belt versus non-Stroke Belt). Community-dwelling, black and white participants from the national Reasons for Geographic And Racial Differences in Stroke (REGARDS) prospective population-based cohort were enrolled between January 2003 and October 2007. Participants were contacted at 6-month intervals for suspected stroke events. For suspected stroke events, it was determined whether the evaluating hospital was a certified PSC. Of 1000 suspected strokes, 204 (20.4%) strokes were evaluated at a PSC. A smaller proportion of women than men (17.8% versus 23.0%; P=0.04), those with a previous stroke (15.1% versus 21.6%; P=0.04), those living in the Stroke Belt (14.7% versus 27.3%; P<0.001), and those in a nonurban area (9.1% versus 23.1%; P<0.001) were evaluated at a PSC. There were no differences by race, education, or income. In multivariable analysis, subjects were less likely to be evaluated at a PSC if they lived in a nonurban area (odds ratio, 0.39; 95% confidence interval, 0.22-0.67) or lived in the Stroke Belt (odds ratio, 0.54; 95% confidence interval, 0.38-0.77) or had a previous stroke (odds ratio, 0.46; 95% confidence interval, 0.27-0.78). Disparities in evaluation by PSCs are predominately related to geographic factors but not to race, education, or low income. Despite an increased burden of cerebrovascular disease in the Stroke Belt, subjects there were less likely to be evaluated at certified hospitals.


[Results of laparoscopic ureterolithotomy depending on the type of laparoscopic approach and location of the stone].
To investigate the results of laparoscopic management of patients with ureterolithiasis, depending on the type of laparoscopic approach and location of the stone. This study is a retrospective analysis of 30 ureterolithiasis patients who underwent laparoscopic ureterolithotomy from 2010 to 2015. Patients were divided into four subgroups depending on the type of laparoscopic approach - transperitoneal (n=17) and retroperitoneal (n=13) and on location of stones - upper ureteral stone (n=20) and mid ureteral stone (n=10). The patients comprised 23 (76.7%) men and 7 (23.3%) women aged from 18 to 68 years (mean age 46.2+/-2.3 years). 15 patients had stones in the right and 15 in left ureters. The groups were comparable by sex, age, the severity of hydronephrosis, body mass index, duration of urolithiasis, comorbidities and previous surgeries (p>0.05). There were no deaths, conversion to open surgery or intraoperative complications. The only statistically significant difference between transperitoneal and retroperitoneal approaches was the absence of postoperative complications (p<0.05). The duration of drainage and hospital stay was significantly shorter in patients with mid ureteral stone than in patients with upper ureteral stone (p<0.05). Surgical management of patients with ureterolithiasis of various locations using laparoscopic ureterolithotomy by different approaches showed positive results of in all cases thus indicating high clinical effectiveness of this method.


Purification and properties of molecular-weight variants of human placental alkaline phosphatase.
1. Alkaline phosphatase of human placenta was purified by a procedure involving homogenization with tris buffer, pH8.6, extraction with butanol, ammonium sulphate fractionation, exposure to heat, ethanol fractionation, gel filtration, triethylaminoethylcellulose anion-exchange chromatography, continuous curtain electrophoresis on paper and equilibrium dialysis. Methods for both laboratory-scale and large-scale preparation were devised. 2. Two major molecular-weight variants designated A and B were separated by molecular sieving with Sephadex G-200 and variant A was purified 4000-fold. 3. Variant B, which comes off the Sephadex G-200 column before variant A, is the electrophoretically slower-moving species on starch gel and is quite heterogeneous. 4. Purified variant A was fairly homogeneous on the basis of electrophoretic studies on starch gel and Sephadex gel, ultracentrifugation and immunodiffusion. 5. The respective molecular weights for variants A and B were 70000 and over 200000 on the basis of sucrose-density-gradient ultracentrifugation. Variant A exhibited a sedimentation coefficient of 4.2s. 6. Crystalline variant B could be converted into fast-moving variant A and vice versa. 7. Kinetic studies indicated no difference between the two variants. These include linear rates of hydrolysis, pH optimum, Michaelis constants and uncompetitive stereospecific l-phenylalanine inhibition. 8. The amino acid compositions of variants A and B and of placental albumin were determined.


Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement.
Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness METHODS: This randomized, open-label, event monitoring board-blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event-free probabilities were estimated using Kaplan-Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (≤5 (recent-onset) or >5 years (chronic illness) since first psychiatric diagnosis). Seventy-seven subjects met the criteria for recent-onset illness; 365 for chronic illness. HRs (95% CI) for treatment failure for oral APs versus PP were 1.73 (0.87-3.45; P = 0.121) for recent-onset and 1.37 (1.02-1.85; P = 0.039) for chronic illness. Most common adverse events for PP versus oral APs were injection site pain (recent-onset, 26% vs. 0%; chronic, 17% vs. 0%), increased weight (14% vs. 6%; 12% vs. 6%), akathisia (14% vs. 9%; 10% vs. 7%), insomnia (12% vs. 17%; 18% vs. 10%) and anxiety (12% vs. 6%; 10% vs. 8%). Although neither pre-planned nor adequately powered, the estimated HRs suggest that the relative advantage of PP over oral APs for reducing the risk for treatment failure may be greater in patients with recent-onset schizophrenia than in those with more chronic illness.


Low-altitude atmospheric wind measurement from the combined Mie and Rayleigh backscattering by Doppler lidar with an iodine filter.
This paper briefly discusses the mobile ground-based incoherent Doppler wind lidar system, with iodine filters as receiving frequency discriminators, developed by the Ocean Remote Sensing Laboratory, Ocean University of Qingdao, China. The presented result of wind profiles in October and November 2000, retrieved from the combined Mie and Rayleigh backscattering, is the first report to our knowledge of wind measurements in the troposphere by such a system, where the required independent measurement of aerosol-scattering ratio can also be performed. A second iodine vapor filter was used to lock the laser to absolute frequency reference for both wind and aerosol-scattering ratio measurements. Intercomparison experiments of the lidar wind profile measurements were performed with pilot balloons. Results showed that the standard deviation of wind speed and wind direction, for the 2-4 km altitude range, were 0.985 m/s and 17.9 degrees, respectively.


A Multi-Omics Approach Using a Mouse Model of Cardiac Malformations for Prioritization of Human Congenital Heart Disease Contributing Genes.
Congenital heart disease (CHD) is the most common type of birth defect, affecting ~1% of all live births. Malformations of the cardiac outflow tract (OFT) account for ~30% of all CHD and include a range of CHDs from bicuspid aortic valve (BAV) to tetralogy of Fallot (TOF). We hypothesized that transcriptomic profiling of a mouse model of CHD would highlight disease-contributing genes implicated in congenital cardiac malformations in humans. To test this hypothesis, we utilized global transcriptional profiling differences from a mouse model of OFT malformations to prioritize damaging, de novo variants identified from exome sequencing datasets from published cohorts of CHD patients. Notch1 +/- ; Nos3 -/- mice display a spectrum of cardiac OFT malformations ranging from BAV, semilunar valve (SLV) stenosis to TOF. Global transcriptional profiling of the E13.5 Notch1 +/- ; Nos3 -/- mutant mouse OFTs and wildtype controls was performed by RNA sequencing (RNA-Seq). Analysis of the RNA-Seq dataset demonstrated genes belonging to the Hif1α, Tgf-β, Hippo, and Wnt signaling pathways were differentially expressed in the mutant OFT. Mouse to human comparative analysis was then performed to determine if patients with TOF and SLV stenosis display an increased burden of damaging, genetic variants in gene homologs that were dysregulated in Notch1 +/- ; Nos3 -/- OFT. We found an enrichment of de novo variants in the TOF population among the 1,352 significantly differentially expressed genes in Notch1 +/- ; Nos3 -/- mouse OFT but not the SLV population. This association was not significant when comparing only highly expressed genes in the murine OFT to de novo variants in the TOF population. These results suggest that transcriptomic datasets generated from the appropriate temporal, anatomic and cellular tissues from murine models of CHD may provide a novel approach for the prioritization of disease-contributing genes in patients with CHD.


DNA Methylation Across the Serotonin Transporter Gene Following Marital Separation: A Pilot Study.
Marital separation and divorce are stressful life transitions associated with increased risk for a range of poor mental and physical health outcomes. A key task for research in this area is to identify individual differences that may index risk for these adverse outcomes. To examine the association between DNA methylation across the serotonin transporter gene (SLC6A4) and self-reported emotional distress following marital separation. Genomic DNA methylation (from buffy coat fractions of whole blood) was quantified in a sample of 47 adults following a recent marital separation; concurrent with the blood draw, participants completed questionnaires on their psychological adjustment to the separation experience. Relatively greater methylation of SLC6A4 was associated with less subjective separation-related psychological distress, and this association held after accounting for participants' age, length of the relationship, time since the separation, and SLC6A4 genotype, b = -211.99, SE = 94.91, p = .03, 95% CI: -402.22, -25.21. Significantly stronger negative associations were observed between methylation and psychological adjustment among participants who had more recently separated from their former partner. Although results derived from small samples must be considered preliminary and hypothesis generating, the current study raises new questions about the role of DNA methylation and psychosocial adaptation to stressful life events such as divorce, and the findings can inform future studies in this research area.


Qualitative Research and Community-Based Participatory Research: Considerations for Effective Dissemination in the Peer-Reviewed Literature.
Qualitative research is appearing with increasing frequency in the public health and medical literature. Qualitative research in combination with a community-based participatory research (CBPR) approach can be powerful. However little guidance is available on how to present qualitative research within a CBPR framework for peer-review publications. This article provides a brief overview of how qualitative research can advance CBPR partnerships and outlines practical guidelines for writing for publication about qualitative research within a CBPR framework to (1) guide partners with little experience publishing in peer-reviewed journals and/or (2) facilitate effective preparation of manuscripts grounded in qualitative research for peer-reviewed journals. We provide information regarding the specific benefits of qualitative inquiry in CBPR, tips for organizing the manuscript, questions to consider in preparing the manuscript, common mistakes in the presentation of qualitative research, and examples of peer-reviewed manuscripts presenting qualitative research conducted within a CBPR framework. Qualitative research approaches have tremendous potential to integrate community and researcher perspectives to inform community health research findings. Effective dissemination of CBPR informed qualitative research findings is crucial to advancing health disparities research.


[Safety of subarachnoid anesthesia during cesarean section in pregnant women with preeclampsia].
The paper contains data on a retrospective observation study of 54 cases of subarachnoid anesthetic management (SAM) for Cesarean section in pregnant women with preeclampsia. The results contradict the generally accepted viewpoint on that the SAM in patients with preeclampsia is not safe due to the negative methods impact on the hemodynamic state. No complications whatsoever were detected in mothers and fetuses of the experimental group, which was apparently due to a suggested set of preventive measures. The study confirmed the SAM safety in patients with preeclampsia.


Differential susceptibility of rat primary neurons and neural stem cells to PFOS and PFOA toxicity.
Per and polifluorinated substances (PFAS) are ubiquitous and persistent contaminants. Studies have indicated that fetuses and infants can be exposed to these chemicals in utero and through breastfeeding. Despite this, limited data about their effects on brain development are available. Here, we compared the effects of perfluoroctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure in rat primary neurons and neural stem cells (NSC). Treatment with 1-250 μM of either of these compounds caused no effects on cell viability or proliferation in primary neurons, while PFOS exposure increased the NSC proliferation already at the lowest concentration tested (1-100 μM). Further analysis showed that both PFOS and PFOA caused morphological alterations of NSC-derived neurons. The neurons derived from NSC treated with either of the PFAS demonstrated a decrease in cell body area. Exposure to 1 and 10 μM PFOA also affected the neurite network and caused an increase in the number of processes and branches per cell. None of the PFAS caused morphological alterations in primary neurons. These data suggest that NSC, mimicking the immature brain, is clearly more susceptible to PFOS and PFOA exposure than the primary neurons. The PFAS-induced alterations in NSC may be related to neurobehavioral alterations observed in rodents developmentally exposed to these compounds, and show the importance to consider the effects of these compounds on human brain development and disease.


Characterization of rat lung epoxide (styrene oxide) hydrase with a modified radioactive assay of improved sensitivity.
The epoxide hydrase assay developed by Oesch et al. (Biochim. Biophys. Acta, 227: 685-691, 1971) using [3H]styrene oxide as substrate was modified in three ways for use with rat lung microsomes: the substrate was purified before use, the volume of the incubation mixture was scaled down 4-fold, and the incubation time was extended to 45 min (activity was found to be linear for at least 60 min). These modifications increased the sensitivity of the assay procedure 75- to 150-fold. The procedure was found to be linear with lung microsomal protein up to at least 1.8 mg protein per incubation mixture. This modified assay for epoxide hydrase was used to characterize the enzyme in rat lung. Its apparent vmax is 0.5 nmole of styrene glycol formed per min per mg microsomal protein, and its apparent Km was 0.11 to 0.25 mM. The pH optimum is around 9.7. Upon subcellular fractionation of lung tissue, expoxide hydrase distributes in the same manner as a marker for the endoplasmic reticulum (reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase) and in a different way from markers for the nuclei, mitochondria, concentric lamellar organelles, lysosomes, Golgi membranes, plasma membrane and soluble cytoplasm. The specific activity of epoxide hydrase in rough and smooth lung microsomes is aobut the same. Treatment i.p. of rats with methylcholanthrene (3 injections of 20 mg/kg), phenobarbital (5 daily injections of 80 mg/kg) or styrene oxide (5 daily injections of 40 mg/kg), did not induce lung microsomal epoxide hydrase activity. 1,1,1-Trichloropropene 2,3-oxide was shown to be an uncompetitive inhibitor, and cyclohexene oxide was a noncompetitive inhibitor of this enzyme. Ethanol and butanol activate the epoxide hydrase of lung microsomes at low concentrations and inhibit it at higher concentrations.


Association of Active and Passive Components of LV Diastolic Filling With Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Mechanistic Insights From Spironolactone Response.
This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e' ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF). In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e' ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction). In 194 patients with HFpEF (64 ± 8 years), a complete echocardiogram (including assessment of myocardial deformation and rotational mechanics) was performed. Echocardiography following maximal exercise was undertaken to assess LV systolic and diastolic responses to stress. A subset of 105 patients with an exercise-induced increase in estimated LV filling pressure were randomly assigned to spironolactone 25 mg (n = 51) or placebo (n = 54) for 6 months. Baseline peak Vo2 was associated with UT (β = 0.19; p = 0.01) and E/e' (β = -0.16; p = 0.03), independent of clinical data and exercise reserve in longitudinal deformation and ventricular-arterial coupling. An increase in peak Vo2 with treatment was independently associated with changes in UT (β = 0.28; p = 0.003) and exertional increase in E/e' (β = -0.23; p = 0.01) from baseline to follow-up. A significant interaction with the use of spironolactone on peak Vo2 was found for E/e' (p = 0.02) but not for UT (p = 0.62). Both active and passive determinants of LV filling, as reflected by UT and E/e', contribute to reduced exercise capacity in HFpEF. Improvement in functional capacity with a 6-month therapy with spironolactone is associated with improvements in both indices. However, the possible mediating effect of this medication is observed only on E/e'.


Oxymatrine Liposomes for Intervertebral Disc Treatment: Formulation, in vitro and vivo Assessments.
Intervertebral disc degeneration (IVDD) is the main cause of modern low back pain, leading to high societal economic costs. To find an effective medical treatment for this disease, oxymatrine liposomes (OMT-LIP) were prepared with the pH-gradient method. Nucleus pulposus (NP) cells from Sprague-Dawley rats were used for the cell experiments. Kunming mice were used for in vivo imaging. LIP were employed to deliver OMT, and the particle size, ζ-potential, morphology, in vitro stability and in vitro release characteristics were evaluated. The OMT-LIP targeting effect was measured by in vivo imaging. Cell Counting Kit-8 assays were used to detect the cytotoxicity of OMT and OMT-LIP on NP cells. Therapeutic efficacy was measured by Western blot, real-time quantitative polymerase chain reaction, and apoptosis assays. Radiologic analysis was performed to evaluate the therapeutic effects in vivo. Orthogonal test results revealed that the mass ratio of egg yolk phosphatidylcholine to cholesterol was the key factor to effectively trap OMT in LIP. Optimal OMT-LIP showed multivesicular structure with entrapment efficiency of 73.4 ± 4.1%, particle size of 178.1 ± 2.9 nm, and ζ-potential of -13.30 ± 2.34 mV. OMT-LIP manifested excellent stability in vitro and presented significantly longer sustained release compared to OMT solution in phosphate-buffered saline (pH 7.4). OMT-LIP conspicuously increased OMT accumulation in the degenerative disc, attenuated NP cell apoptosis, reduced the expression of matrix metalloproteinases 3/9 and interleukin-6, and decreased degradation of type II collagen. In in vivo study, X-ray demonstrated that OMT-LIP inhibited IVDD. OMT-LIP may be a useful treatment to alleviate disc inflammation and IVDD.


Phase-constrained data extrapolation method for reduction of truncation artifacts.
The authors present an improvement to a sigma-filter extrapolation method for the reconstruction of magnetic resonance (MR) images from symmetric discrete Fourier data. By making use of the phase information in the image data, the proposed method can overcome the data inconsistency problem of the original method for handling MR image data with large phase variations, such as those obtained in gradient-echo pulse sequences. Reconstruction results show that its performance is comparable with that of the modified complex sigma-filter method proposed previously to handle the inconsistency problem. However, the new approach has the advantage of reducing computation time by a factor of two with use of a sigma filter applied to real instead of complex images. It is expected that this method will be more practical for use in clinical MR imaging systems.


Corruption and its relation to prevalence and death due to noncommunicable diseases and risk factors: a global perspective.
To describe the relation between corruption indicators and statistics on noncommunicable diseases and their risk factors by continent. An ecological study was conducted to examine the relation of the GINI coefficient, the Country Policy and Institutional Assessment (CPIA), and the Corruption Perception Index (CPI) with noncommunicable diseases, using the Spearman's rank correlation test. There is a moderate and positive correlation between Corruption Perception Index and cause of death due to noncommunicable diseases and risk factors for these diseases (r = 0.532), prevalence of schizophrenia (r = 0.526), bipolar disorder (r = 0.520), and eating disorders (r = 0.677). There is a moderate negative association between the GINI index and cause of death due to noncommunicable diseases (r = -0.571) and smoking prevalence (r = -0.502), and between the Corruption Perception Index and mortality caused by cardiovascular diseases, cancer, diabetes, or chronic respiratory diseases between the exact ages of 30 and 70 years (r = -0.577) and malnutrition prevalence (r = -0.602). This study indicates a correlation between corruption and noncommunicable diseases and their risk factors. This suggests that the high prevalence of noncommunicable diseases and risk factors could be related with political practices that negatively impact the population. Further research should study the weight of these associations, to take action on the way corruption is impacting on the health of societies.


The BfT-GermVet monitoring program--aims and basics.
To determine the current status of antimicrobial susceptibility of bacterial pathogens from animals in Germany, the Bff-GermVet monitoring program was initiated as a complementary program to the German national monitoring program GERM-Vet conducted by the Federal Office of Consumer Protection and Food Safety (BVL). In the Bff-GermVet program, a total of 1,626 bacterial strains, obtained during a 27-month period (01/2004-03/2006) from 31 indications, was screened for susceptibility against 22 antimicrobial agents and two combinations of antimicrobial agents. Selected bacteria were additionally tested for their susceptibility against additional three combinations of antimicrobial agents and the corresponding single substances. This paper describes the overall aims and the structure of the program with particular reference to the sampling strategy, the methodology for susceptibility testing and the interpretive criteria used for evaluation of the results.


[A case of hepatosplenic gammadelta T cell lymphoma].
Hepatosplenic gammadelta T cell lymphoma represents rare, often aggressive type of malignant peripheral T-cell lymphoma, which is characterized by expressing T-cell-associated markers CD2, CD3 and gammadelta T-cell receptor, and nonactivated cytotoxic cell phenotype (TIA-1+, granzyme B-). The pathological findings of a liver biopsy specimen revealed the diffuse infiltration of lymphocytes in the sinusoids and the aspiration biopsy from spleen revealed the diffuse infiltration of lymphocytes in the red pulp, not shaped to the nodes, often resulted in the misdiagnosis. Recently, by analyzing the immunophenotype and TCR rearrangement from liver, spleen and bone marrow, a case of adult hepatosplenic gammadelta T cell lymphoma was diagnosed. In combination with references, It is belived that immunophenotype and TCR rearrangement are necessary means to diagnosis hepatosplenic gammadelta T cell lymphoma.


Implications of the current tuberculosis treatment landscape for future regimen change.
The current tuberculosis (TB) treatment landscape has been studied extensively, but researchers rarely consider how it creates challenges or opportunities for future regimen change. In 166 stakeholder interviews in the TB high-burden countries (HBCs), we investigated areas of first-line TB treatment and control that would affect, and be affected by, a future TB regimen change. Responses were compared with existing standardized data. Public sector regimens are converging towards a single standard, which facilitates comparison with a single control arm from clinical trials. However, final product design is challenging if the goal is fixed-dose combinations and patient kits, whose current widespread use addresses continuing weaknesses in drug management. Any product must address broad groups, as relatively low levels of drug susceptibility testing (DST) do not allow for individualized therapy. Finally, the protection of new drugs from the development of resistance will be challenging, as the implementation of directly observed therapy and public-private mix programs is incomplete, and substantial private sectors have been identified as early adopters of these drugs. Health systems for TB treatment and control must be improved not only to allow better implementation of current treatments but also to set the stage for implementation of new, improved TB regimens.


Therapeutic effects of combined treatment with ribavirin and tiazofurin on experimental autoimmune encephalomyelitis development: clinical and histopathological evaluation.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) and the helpful tool in preclinical testing of various substances considered for treatment of this human CNS disease. Ribavirin (R) and tiazofurin (T) are purine nucleoside analogues, with the broad spectrum of anti-viral, anti-tumoral and anti-inflammatory properties. We proposed that combined treatment with RT, administrated during the effector phase of EAE, would attenuate disease severity, both clinically and pathologically. Ribavirin was given daily at a dosage of 30 mg/kg and tiazofurin was given at a dosage of 10 mg/kg every other day for 15 days. We detected amelioration of clinical signs and faster recovery in the RT group compared to the control group. Immunohistochemical analyses revealed that RT treatment decrease the number of T cells, macrophages and microglia. In the controls, we detected reactive type of microglia, while in the RT group we noticed ramified/resting form. Demyelination areas and axonal damage were not recorded in the RT group, in contrast to the control group where multiple areas of demyelination zones and axonal loss were found. RT combination treatment suppresses ongoing EAE, prevents demyelination and axonal loss, and therefore may well be the potential therapy for the treatment of MS.


The yeast molecular chaperone, Hsp104, influences transthyretin aggregate formation.
Patients with the fatal disorder Transthyretin Amyloidosis (ATTR) experience polyneuropathy through the progressive destruction of peripheral nervous tissue. In these patients, the transthyretin (TTR) protein dissociates from its functional tetrameric structure, misfolds, and aggregates into extracellular amyloid deposits that are associated with disease progression. These aggregates form large fibrillar structures as well as shorter oligomeric aggregates that are suspected to be cytotoxic. Several studies have shown that these extracellular TTR aggregates enter the cell and accumulate intracellularly, which is associated with increased proteostasis response. However, there are limited experimental models to study how proteostasis influences internalized TTR aggregates. Here, we use a humanized yeast system to recapitulate intracellular TTR aggregating protein in vivo. The yeast molecular chaperone Hsp104 is a disaggregase that has been shown to fragment amyloidogenic aggregates associated with certain yeast prions and reduce protein aggregation associated with human neurogenerative diseases. In yeast, we found that TTR forms both SDS-resistant oligomers and SDS-sensitive large molecular weight complexes. In actively dividing cultures, Hsp104 has no impact on oligomeric or large aggregate populations, yet overexpression of Hsp104 is loosely associated with an increase in overall aggregate size. Interestingly, a potentiating mutation in the middle domain of Hsp104 consistently results in an increase in overall TTR aggregate size. These data suggest a novel approach to aggregate management, where the Hsp104 variant shifts aggregate populations away from toxic oligomeric species to more inert larger aggregates. In aged cultures Hsp104 overexpression has no impact on TTR aggregation profiles suggesting that these chaperone approaches to shift aggregate populations are not effective with age, possibly due to proteostasis decline.


Acute variceal bleeding portends poor outcomes in patients with acute-on-chronic liver failure: a propensity score matched study from the APASL ACLF Research Consortium (AARC).
Limited data exist regarding outcomes of acute variceal bleeding (AVB) in patients with acute-on-chronic liver failure (ACLF), especially in those with hepatic failure. We evaluated the outcomes of AVB in patients with ACLF in a multinational cohort of APASL ACLF Research Consortium (AARC). Prospectively maintained data from AARC database on patients with ACLF who developed AVB (ACLF-AVB) was analysed. This data included demographic profile, severity of liver disease, and rebleeding and mortality in 6 weeks. These outcomes were compared with a propensity score matched (PSM) cohort of ACLF matched for severity of liver disease (MELD, AARC score) without AVB (ACLF without AVB). Of the 4434 ACLF patients, the outcomes in ACLF-AVB (n = 72) [mean age-46 ± 10.4 years, 93% males, 66% with alcoholic liver disease, 65% with alcoholic hepatitis, AARC score: 10.1 ± 2.2, MELD score: 34 (IQR: 27-40)] were compared with a PSM cohort selected in a ratio of 1:2 (n = 143) [mean age-44.9 ± 12.5 years, 82.5% males, 48% alcoholic liver disease, 55.7% alcoholic hepatitis, AARC score: 9.4 ± 1.5, MELD score: 32 (IQR: 24-40)] of ACLF-without AVB. Despite PSM, ACLF patients with AVB had a higher baseline HVPG than without AVB (25.00 [IQR: 23.00-28.00] vs. 17.00 [15.00-21.75] mmHg; p = 0.045). The 6-week mortality in ACLF patients with or without AVB was 70.8% and 53.8%, respectively (p = 0.025). The 6-week rebleeding rate was 23% in ACLF-AVB. Presence of ascites [hazard ratio (HR) 2.2 (95% CI 1.03-9.8), p = 0.026], AVB [HR 1.9 (95% CI 1.2-2.5, p = 0.03)], and MELD score [HR 1.7 (95% CI 1.1-2.1), p = 0.001] independently predicted mortality in the overall ACLF cohort. Development of AVB confers poor outcomes in patients with ACLF with a high 6-week mortality. Elevated HVPG at baseline represents a potential risk factor for future AVB in ACLF.