Subdivisions of the dopamine-containing A8-A9-A10 complex identified by their differential mesostriatal innervation of striosomes and extrastriosomal matrix.
The mesostriatal projections from the dopamine-containing cells groups A8, A9 and A10 have been studied in the cat in relation to the histochemical compartments known to exist in the striatum. In order to do this, we made stereotaxic injections in the substantia nigra of either [3H]proline-[3H]leucine, [35S]methionine, wheat germ agglutinin-horseradish peroxidase, or the two last tracers combined, and compared the location of anterograde labeling in the striatum to the locations of striosomes and extrastriosomal matrix identified by their low or high content, respectively, of the enzyme acetylcholinesterase. A discrete innervation of dorsolateral striosomes by a caudal densocellular subdivision of the substantia nigra pars compacta was found. This densocellular zone of the pars compacta was readily identifiable in sections stained for tyrosine hydroxylase-like immunoreactivity and corresponded to the uniquely acetylcholinesterase-poor zone detected in the substantia nigra pars compacta in serially adjacent sections stained for this enzyme. Selective anterograde labeling of the extrastriosomal matrix occurred in cases with injection sites centered in cell group A8. Tracer deposits in cell group A10 also elicited a preferential labeling of the extrastriosomal matrix, but this innervation was sparse compared to the prominent labeling of fibers in the ventral striatum. An almost exclusive innervation of caudal and ventral striosomes of the head of the caudate nucleus occurred after a deposit of tracer in the pars lateralis of the substantia nigra. Mixed labeling of striosomes and matrix occurred with injection sites centered in the rostral, cell-sparse part of the pars compacta of the substantia nigra. Clusters of tyrosine hydroxylase-immunoreactive neurons within this zone, most likely representing finger-like extensions of the caudal densocellular zone of the pars compacta, might have accounted for part of the striosomal labeling in these cases. We conclude that different subdivisions of the A8-A9-A10 dopamine-containing cell complex of the cat's mesencephalon project preferentially to striosomes or to extrastriosomal matrix. On this basis we suggest that there may be different functional channels in the mesostriatal projection, including, from cell group A8, a channel providing dopaminergic modulation of sensorimotor processing in the striatal matrix, and, from the densocellular zone of the substantia nigra pars compacta, a channel leading to limbic-related mechanisms represented in the striosomal system.


Mortality analysis of burns in a developing country: a CAMEROONIAN experience.
Burns are a serious public health problem worldwide accounting for an estimated 265,000 deaths annually from fires alone. The vast majority (96%) of deaths from fire-related burns occur in low- and middle-income countries and burns are one of the leading causes of disability-adjusted life-years (DALYs) in the developing world. Most burn centres are situated in large cities and are inadequate for the high incidence of injuries. An 8 year review of 440 patients in the Douala General Hospital, showed that the majority of patients burned were males (n = 281, 68.9%), the mean age was 25.2 ± 17.77 years with an admission rate of 69.5% (306 patients). The modal and median age were 31.0 years and 25.0 years respectively, interquartile range (0.4-82). Majority of burns (n = 237, 53.9%) had burn surface area ≥ 10%, most burns were 2nd degree (n = 215, 48.9) and the commonest burn agents were flames (n = 170, 37.3%), electricity (n = 119, 26.3%) and water (n = 114, 25.2%). The paucity of data on burn mortality in Cameroon motivated this study and is aimed at determining the mortality rate, causes and factors associated with death of burnt patients in the burn unit of the Douala General Hospital (DGH). It was a retrospective observational study carried out from the 1st of January 2008 to the 31st of December 2015 in the Burn Unit of the Douala General Hospital. An adapted questionnaire was used to collect demographic data, burn agents, burn depth; diagnostic delay, burn surface area, complications, comorbidity, mortality and its causes. Data was transferred to Microsoft Excel 2015 and the Statistical Package for Social Sciences (SPSS) version 20.0 for data analysis. During this 8 year period, 440 patients were studied and the mortality rate was 23.4% (103 patients). The fatal burn agents were, flames (n = 69, 67.0%), electricity (n = 15, 14.6%), water (n = 12, 11.6%), contact (n = 4, 3.9%), Oil (n = 2, 1.9%) and chemicals (n = 1, 1.0%). The causes of death were shock (n = 36, 35.0%), sepsis (n = 25, 24.3%), acute respiratory distress (n = 25, 24.3%), acute renal failure (n = 6, 5.8%), severe anaemia (n = 4, 3.9%) and unrecorded causes (n = 7, 6.7%). A quarter of all patients died mostly from flame burns and to a lesser extent, electricity and scalds. Increase in burn depth and burn surface area worsened the prognosis. Shock (the commonest cause of death), sepsis, acute respiratory distress, acute renal failure and wound infection were significantly associated with mortality.


Predicting Quadruple Semitendinosus Graft Size for Anterior Cruciate Ligament Reconstruction by Patient Anthropometric Variables: A Cohort Study of 280 Cases.
Pre-operative identification of patients with inadequate hamstring graft for anterior cruciate ligament reconstruction is still a subject of interest. The purpose of this study is to correlate dimension of a harvested dimensions graft with patient physical anthropometric variables. This cohort study included 280 patients (male = 226, female = 54) scheduled for primary anterior cruciate ligament (ACL) reconstruction. Interrelationships between quadruple semitendinosus (ST) graft and anthropometric parameters (age, sex, height, weight, and BMI) were assessed using Pearson Correlation test and regression analysis. Difference among gender was analysed using Mann Whitney and t test. The observed graft diameter was also compared with the literature using Bland - Altman plot. Mean age of cohort was 29 years (range, 17-50 years), mean height was 1.69m (range, 1.6-1.9m), mean weight was 75 kg (range, 50-116kg) and mean BMI was 26kg/m2 (range 16.65-40.40kg/m2). Mean quadruple length of harvested ST graft was 7cm (7.1±0.6 cm, range, 5.6-8.8cm) and mean diameter was 8mm (8.2±0.8mm, range, 6.5-10mm). Only height and weight were significantly correlated with graft length and diameter in both sex (p value <0.05). Female, compared to male, had significantly smaller (p<0.0001) and thinner graft (p<0.0001). There was a strong agreement between the literature and our observed graft diameter, but with an overestimated graft diameter in 18.5% of the cases. Among anthropometric parameter, only height and weight had moderate positive correlation with graft diameter. Males had longer and wider ST graft in contrast to age-matched female group.


On the distribution and inventories of radionuclides in dated sediments around the Swedish coast.
The activity concentrations and distribution of 137Cs, 238Pu, 239+240Pu, 241Am, and 210Pb was determined by the analysis of six sediment cores from the Baltic Sea and Kattegat. The chronology of the sediment cores has been used to evaluate the origin and time trend of the radionuclide sources in these sediments. The sediment cores were dated with a 210Pb model and the results were validated with fallout peaks, assumed to originate from the global nuclear weapons testing and the Chernobyl accident. Source identification, using the isotopic and radionuclide activity ratios, showed that the Chernobyl accident is the main source of 137Cs in the Baltic Sea; for 239+240Pu and 241Am the dominant source was shown to be fallout from nuclear weapons tests. For 238Pu and 241Am the Chernobyl accident had a significant impact on the direct fallout into the Baltic Proper, with up to a 65% contribution in the sediment slices dated to 1986. In these sediment slices the maximum activity ratios of 238Pu/239+240Pu and 241Am/239+240Pu were 0.314 ± 0.008 and 1.29 ± 0.06, respectively. The ratios clearly deviate from the corresponding ratios for global nuclear weapons fallout (around 0.028 and 0.54, respectively). Calculated inventories were 63-175 Bq·m-2 for 239+240Pu, 2.8-7.8 for 238Pu Bq·m-2 and 0.92-44.4 kBq·m-2 for 137Cs. Different fallout patterns for 137Cs and plutonium isotopes from the Chernobyl accident were confirmed through depth profiles analyses. The maximum inventory of 137Cs was observed in the Bothnian Sea, while Chernobyl-derived plutonium was found to be mostly present in Northern Baltic Proper. The radionuclides distribution in the depth profiles shows how contaminated water affects the sediment as it passes sampling stations according to the current circulation pattern in the Baltic Sea. Additionally, the effect of increased activity concentrations from of river discharges in the most contaminated area in the Bothnian Sea was observed.


[Anxiety in children and adolescents with pervasive developmental disorder without mental retardation: review of literature].
Anxiety is highly prevalent in Pervasive Developmental Disorder (PDD) without mental retardation but is too often misdiagnosed. The authors suggest a critical review of current data of the PDD without mental retardation in children and adolescents, in order to summarize research published in this field. After describing specific features, this article tackles the issue of prevalence of anxiety among this population, then deals with present-time assessment and treatments of comorbid anxiety. This review was based on a systematic search of the main online databases (Science Direct, PsychInfo, Medline and Pubmed) in order to compile surveys published on Asperger syndrome and high-functioning autism-related anxiety among children and adolescents. This study focuses on papers published between 1995 and 2010, using strict diagnostic criteria for anxiety and PDD, and a controlled group, with the exception of pharmacological studies because none are controlled. We found seven studies assessing the prevalence of anxiety among children and adolescents with PDD, four assessment tools and 12 treatments. Anxiety disorders were shown in 42% of children and adolescents with PDD without mental retardation. This disorder is related to age and level of cognitive functioning and is likely to affect PDD without mental retardation as children and adolescents with anxiety disorder without PDD. This review highlights a major problem: assessment of anxiety in PDD without mental retardation. Actually, only two PDD adapted instruments have been found: the Autism Co-Morbidity Interview Present and Lifetime Version (ACI-PI) and the Stress Survey Schedule (SSS) for persons with autism. Such tools being methodologically limited, the diagnosis of anxiety disorder is all the more difficult to establish. Consequently, considering suitable treatment is not always proposed. Recent surveys show how profitable pharmacological treatment and behavioral intervention like Cognitive-Behavior Therapy (CBT) or psychosocial treatments are. However, important methodological limitations are evoked: there is no control study assessing the efficiency of a pharmacological treatment in Asperger syndrome and high-functioning autism. Besides, the research on how profitable cognitive and behavioral treatment is, gives heterogeneous results. Finally, social skills' training does not treat anxiety disorder directly, but skills abilities that are the most important disabilities in PDD without mental retardation. Therefore, authors advocate adapting treatment in order to treat anxiety disorder. The research revealed an important need to create new assessment instruments suitable to PDD without mental retardation in order to facilitate the co-morbidity diagnosis. This survey also underlines the necessity to develop controlled research testing the efficiency of such treatments as pharmacological ones, cognitive and behavioral therapies as well as social skills training.


Improved Cardiac Proton Magnetic Resonance Spectroscopy at 3 T Using High Permittivity Pads.
The aim of this study was to determine whether high permittivity (HP) pads can be used to increase the signal-to-noise ratio (SNR) of cardiac proton magnetic resonance spectroscopy at 3 T, allowing faster data acquisition. The institutional review board approved the study protocol, and written informed consent was obtained from all participants. In 22 healthy volunteers, water-suppressed localized spectra were acquired in the interventricular septum without and with HP pads. The SNR and myocardial triglyceride content (MTGC) were measured without and with the HP pads, and the results were compared with a paired sample Student t test. Application of HP pads increased mean (SD) SNR from 27.9 (15.6) to 42.3 (24.4) (P < 0.0001), a mean gain of 60%. The acquisition time can thereby be reduced from just under 5 minutes to just under 2 minutes while maintaining the same SNR. The mean (SD) MTGC was 0.39% (0.17%) without pads and 0.38% (0.15%) with pads (P = 0.83) for the healthy volunteers, showing that no bias is introduced by using the pads. No difference in spectral linewidth was measured (P = 0.80), the values being 17.4 (4.9) Hz without and 17.1 (3.2) Hz with pads. Both transmit and receive maps showed increases in sensitivity due to the presence of the HP pads. High permittivity pads improve cardiac proton magnetic resonance spectroscopy at 3 T by increasing the SNR on average by 60%, which can be used to reduce data acquisition time significantly, allowing fast assessment of MTGC without compromising spectral quality. The SNR increase arises primarily from the increase in receive sensitivity of the phased array, which is more closely coupled to the body via the HP pads. In addition, the transmit efficiency is also increased, allowing shorter or lower power radiofrequency pulses.


Evidence for a causal role by mouse mammary tumour-like virus in human breast cancer.
We have reviewed the evidence relevant to mouse mammary tumour viruses (MMTV) and human breast cancer. The prevalence of MMTV- like gene sequences is 15-fold higher in human breast cancer than in normal human breast tissue controls and is present in up to 40% of human breast cancers. MMTV-like gene sequences can be identified in benign breast tissues 1-11 years before the development of positive MMTV-like breast cancer in the same women. The prevalence of MMTV antibodies in sera from women with breast cancer is 5-fold higher than in normal women. MMTV can infect human breast epithelial cells and integrate at random into the human genome located in those cells. MMTV-like gene sequences are present in human milk from normal lactating women and with increased prevalence in milk from women at risk of breast cancer. MMTV-like virus associated human breast cancer has strikingly similar features to MMTV-associated mouse mammary tumours. These features include almost identical nucleotide sequences and structure of the MMTV genome, histology, superantigen expression, MMTV infection of B and T lymphocytes and hormone dependence. MMTV-like gene sequences have also been identified in dogs, cats, monkeys, mice and rats. Saliva has been identified as the most plausible means of transmission from human to human and possibly from dogs to humans. The evidence meets the classic causal criteria. A causal role for MMTV-like viruses in human breast cancer is highly likely.


Effect of multi-component school-based program on body mass index, cardiovascular and diabetes risks in a multi-ethnic study.
Mexico occupies one of the first places worldwide in childhood obesity. Its Mestizo and Indigenous communities present different levels of westernization which have triggered different epidemiological diseases. We assessed the effects of a multi-component school-based intervention program on obesity, cardiovascular and diabetes risk factors. A physical activity, health education and parent involvement (PAHEPI) program was developed and applied in six urban (Mestizo ethnic group) and indigenous (Seri and Yaqui ethnic groups) primary schools for 12 weeks. A total of 320 children aged 4-12 years participated in intervention program; 203 under Treatment 1 (PAHEPI program) and 117, only from Mestizo groups, under Treatment 2 (PAHEPI+ school meals). For Body Mass Index (BMI), cardiovascular and diabetes factors, pairwise comparisons of values at baseline and after treatments were done using Wilcoxon signed rank test. Generalized linear models were applied to assess the intervention effect by age, sex and nutritional status in relation to ethnicity and treatment. We observed improvements on BMI in children with overweight-obesity and in triglycerides in the three ethnic groups. The Mestizo ethnic group showed the largest improvements under Treatment 2. While Seris showed improvements only in cardiovascular risk factors, Yaquis also showed improvements in diabetes risk factors, though not in BMI. This study showed that the same intervention may have positive but different effects in different ethnic groups depending on their lifestyle and their emerging epidemiological disease. Including this type of intervention as part of the school curriculum would allow to adapt to ethnic group in order to contribute more efficiently to child welfare. This study was retrospectively registered under the identifier NCT03768245 .


Pictograms are more effective than verbal descriptors in Spanish for bloating and distension.
There is no translation for bloating in Spanish, and distension is very technical. To evaluate pictograms for assessing bloating/distension in patients with general gastroenterology (Study 1, n = 88) and in those with irritable bowel syndrome [IBS] (Study 2: n = 144), and to correlate them with verbal descriptors (VDs) and physician's diagnosis (PDx). Patients answered the Rome III Questionnaire with VDs and pictograms, and were consulted by two gastroenterology fellows (PDx). Correlations were conducted with Cohen's kappa, and ROC curves were used to contrast pictograms and VDs with PDx. "Inflammation" was the most frequent VDs, while distension was commonly interpreted as a sensation ("inflammation") and/or increased abdominal girth. In patients not reporting bloating/distension with VDs, pictograms detected these symptoms in (Study 1 and Study 2) 82.2 and 89.6% of patients. In addition, pictograms showed a positive agreement with PDx, kappa: 0.63 (p < 0.0001) and 0.8 (p < 0.0001); and a negative agreement with VD, kappa: -0.45 (p = 0.05) and -0.1 (p = 0.2), respectively, in studies 1 and 2. Pictograms were more sensitive and specific than VDs (Study 1: ROC = 0.90 (95% CI: 0.80-0.96), p < 0.0001 versus 0.74 (0.62-0.88), p < 0.0001; Study 2: 0.99 (0.98-1.00), p = 0.004 versus 0.32 (0.10-0.54), p = 0.294). Pictograms are more effective than Spanish VDs for bloating/distension in patients consulting for gastroenterology problems and those with IBS, supporting their usefulness in the clinic and research studies.


The impact of missense mutation in PIGA associated to paroxysmal nocturnal hemoglobinuria and multiple congenital anomalies-hypotonia-seizures syndrome 2: A computational study.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The disease is caused by the deficiency of two glycosylphosphatidylinositols (GPI)-anchored proteins (CD55 and CD59) in the hemopoietic stem cells. The deficiency of GPI-anchored proteins has been associated with the somatic mutations in phosphatidylinositol glycan class A (PIGA). However, the mutations that do not cause PNH is associated with the multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2). To best of our knowledge, no computational study has been performed to explore at an atomistic level the impact of PIGA missense mutations on the structure and dynamics of the protein. Therefore, we focused our study to provide molecular insights into the changes in protein structural dynamics upon mutation. In the initial step, screening for the most pathogenic mutations from the pool of publicly available mutations was performed. Further, to get a better understanding, pathogenic mutations were mapped to the modeled structure and the resulting protein was subjected to 100 ns molecular dynamics simulation. The residues close to C- and N-terminal regions of the protein were found to exhibit greater flexibility upon mutation. Our study suggests that four mutations are highly effective in altering the structural conformation and stability of the PIGA protein. Among them, mutant G48D was found to alter protein's structural dynamics to the greatest extent, both on a local and a global scale.


Inheritance of allozyme variants in bishop pine (Pinus muricuta D. Don).
Isozyme phenotypes are described for 45 structural loci and 1 modifier locus in bishop pine (Pinus muricata D. Don,) and segregation data are presented for a subset of 31 polymorphic loci from 19 enzyme systems. All polymorphic loci had alleles that segregated within single-locus Mendelian expectations, although one pair of alleles at each of three loci showed significant segregation distortion. The consistency of resolution and segregation at many loci in bishop pine makes electrophoretic analyses feasible for many purposes in this species.


Staging laparoscopy using ALA-mediated photodynamic diagnosis improves the detection of peritoneal metastases in advanced gastric cancer.
This study evaluated the usefulness of photodynamic diagnosis (PDD) using oral 5-aminolevulinic acid (ALA) for the detection of peritoneal metastases in advanced gastric cancer. First, the numbers of peritoneal metastatic nodules that were visible under conventional white light (WL) and ALA-induced fluorescence (ALA-F) were quantified in a mouse model of peritoneal metastasis to compare the tumor detection rate. Next, staging laparoscopy (SL) using ALA-PDD was performed in 13 advanced gastric cancer patients with serosa-invading tumors, and the detection sensitivity of ALA-PDD was compared to the observations using WL. The tumor detection rate using ALA-F was significantly higher than the detection rate using WL (72% vs. 39%, respectively, P < 0.0001). Peritoneal metastases were detected in five patients using SL with ALA-PDD, and liver metastases were detected in one patient. These metastases were confirmed using histological examination. Three metastatic lesions that were invisible under WL were detected under ALA-F. This study demonstrated that SL with ALA-PDD improved the detection sensitivity for peritoneal metastases. ALA-PDD may be an important technique for the preoperative staging of advanced gastric cancer, and ALA-PDD will provide useful information for the selection of therapeutic modality.


Discovery and optimization of a series of small-molecule allosteric inhibitors of MALT1 protease.
We describe a series of potent and highly selective small-molecule MALT1 inhibitors, optimized from a High-Throughput Screening hit. Advanced analogues such as compound 40 show high potency (IC50: 0.01 µM) in a biochemical assay measuring MALT1 enzymatic activity, as well as in cellular assays: Jurkat T cell activation (0.05 µM) and IL6/10 secretion (IC50: 0.10/0.06 µM) in the TMD8 B-cell lymphoma line. Compound 40 also inhibited cleavage of the MALT1 substrate RelB (IC50: 0.10 µM). Mechanistic enzymology results suggest that these compounds bind to the known allosteric site of the protease.


Association between bicycle helmet legislation, bicycle safety education, and use of bicycle helmets in children.
To determine the association between bicycle helmet legislation and bicycle safety education and the use of bicycle helmets by children under age 16 years. Anonymous questionnaire and direct observations of bicycle helmet use. Four predominantly white, upper-middle class suburbs of Cleveland, Ohio. All students in grades 1 through 7 attending public school on the day of the survey and children riding bicycles in a direct observational study. Beachwood had bicycle helmet legislation and safety education. Orange had only bicycle helmet legislation. Pepper Pike and Moreland Hills did not have bicycle helmet legislation or safety education. In Beachwood, 416 (67.6%) of 615 children who owned a bicycle reported always wearing their helmets, and 72 (85%) of 85 children directly observed were wearing bicycle helmets. In Orange, 103 (37.2%) of 277 children who owned bicycles reported always wearing helmets, whereas 41 (17.9%) of 229 children in Moreland Hills and 78 (21.5%) of 362 children in Pepper Pike reported always wearing helmets. Helmet use was significantly (P < .001) higher in Beachwood, with legislation and education, than in the other communities; helmet use was significantly (P < .001) higher in Orange, with legislation alone, than in Moreland Hills and Pepper Pike, with no programs. There was a dramatic association between reports of increased helmet use and bicycle helmet legislation plus education; the association was stronger than that found with legislation only.


Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function.
The androgen receptor (AR) is a nuclear hormone receptor superfamily member that conveys both trans repression and ligand-dependent trans-activation function. Activation of the AR by dihydrotestosterone (DHT) regulates diverse physiological functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation. The histone acetylases p300 and P/CAF directly acetylate the AR in vitro at a conserved KLKK motif. To determine the functional properties governed by AR acetylation, point mutations of the KLKK motif that abrogated acetylation were engineered and examined in vitro and in vivo. The AR acetylation site point mutants showed wild-type trans repression of NF-kappa B, AP-1, and Sp1 activity; wild-type sumoylation in vitro; wild-type ligand binding; and ligand-induced conformational changes. However, acetylation-deficient AR mutants were selectively defective in DHT-induced trans activation of androgen-responsive reporter genes and coactivation by SRC1, Ubc9, TIP60, and p300. The AR acetylation site mutant showed 10-fold increased binding of the N-CoR corepressor compared with the AR wild type in the presence of ligand. Furthermore, histone deacetylase 1 (HDAC1) bound the AR both in vivo and in cultured cells and HDAC1 binding to the AR was disengaged in a DHT-dependent manner. MEKK1 induced AR-dependent apoptosis in prostate cancer cells. The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved AR acetylation site contributes to a pathway governing prostate cancer cellular survival. As AR lysine residue mutations that abrogate acetylation correlate with enhanced binding of the N-CoR repressor in cultured cells, the conserved AR motif may directly or indirectly regulate ligand-dependent corepressor disengagement and, thereby, ligand-dependent trans activation.


Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy.
In earlier studies we reported the finding of a tumor-associated peptide that also occurred at high concentrations in early amniotic fluid. Determination of the N-terminal sequence of this peptide revealed that it is closely related or identical to the pancreatic secretory trypsin inhibitor. Therefore, the peptide is called tumor-associated trypsin inhibitor (TATI). The concentration of TATI was determined by radioimmunoassay in the urine of 148 patients with various forms of gynecologic malignancy and in a reference population consisting of 98 patients with non-malignant gynecologic disease, and also in 40 patients with severe infections or inflammatory disease. In the reference population, the median urinary concentration of TATI was 22 micrograms/g creatinine and the central 95% reference interval was 7-50 micrograms/g creatinine. Elevated urinary levels were observed in 53% of all patients with gynecologic cancer, in 63% of those with active disease and 26% of those in clinical remission. The highest urinary TATI level (11,000 micrograms/g creatinine) was over 200 times the upper limit of the reference range. Patients with cervical cancer had the highest frequency of elevated values. Increased excretion of TATI was also observed in patients with severe bronchopulmonary infections and pancreatitis. Although increased excretion of TATI is not cancer-specific, the distinction by elevated levels of TATI between malignant and nonmalignant gynecologic disease is better than by most other putative tumor markers, and the increased excretion of TATI in patients with active disease can be important for the understanding of tumor biology.


Follicular helper T cells in immunity and systemic autoimmunity.
Follicular helper T (T(FH)) cells are essential for B-cell maturation and immunoglobulin production after immunization with thymus-dependent antigens. Nevertheless, the development and function of T(FH) cells have been less clearly defined than classic CD4(+) effector T-cell subsets, including T-helper-1 (T(H)1), T(H)2 and T(H)17 cells. As such, our understanding of the genesis of T(FH) cells in humans and their role in the development of autoimmunity remains incomplete. However, evidence from animal models of systemic lupus erythematosus (SLE) and patients with systemic autoimmune diseases suggests that these cells are necessary for pathogenic autoantibody production, in a manner analogous to their role in promotion of B-cell maturation during normal immune responses. In this Review, I discuss the findings that have increased our knowledge of T(FH)-cell development and function in normal and aberrant immune responses. Such information might improve our understanding of autoimmune diseases, such as SLE, and highlights the potential of T(FH) cells as therapeutic targets in these diseases.


Genetic variations in adiponectin levels and dietary patterns on metabolic health among children with normal weight versus obesity: the BCAMS study.
Adiponectin represents an important link between adipose tissue dysfunction and cardiometabolic risk in obesity; however, there is a lack of data on the effects of adiponectin-related genetic variations and gene-diet interactions on metabolic disorders in children. We aimed to investigate possible interactions between adiponectin-related genetic variants and habitual dietary patterns on metabolic health among children with normal weight versus overweight/obesity, and whether these effects in childhood longitudinally contribute to metabolic risk at follow-up. In total, 3,317 Chinese children aged 6-18 at baseline and 339 participants at 10-year follow-up from the Beijing Child and Adolescent Metabolic Syndrome study cohort were included. Baseline lifestyle factors, plasma adiponectin levels, and six adiponectin-related genetic variants resulting from GWAS in East Asians (loci in/near ADIPOQ, CDH13, WDR11FGF, CMIP, and PEPD) were assessed for their associations with the metabolic disorders. Being metabolically unhealthy was defined by exhibiting any metabolic syndrome component. Among the six loci, ADIPOQ rs6773957 (OR 1.26, 95% CI:1.07-1.47, P = 0.004) and adiponectin receptor CDH13 rs4783244 (0.82, 0.69-0.96, P = 0.017) were correlated with metabolic risks independent of lifestyle factors in normal-weight children, but the associations were less obvious in those with overweight/obesity. A significant interaction between rs6773957 and diet (Pinteraction = 0.004) for metabolic health was observed in normal-weight children. The adiponectin-decreasing allele of rs6773957 was associated with greater metabolic risks in individuals with unfavorable diet patterns (P < 0.001), but not in those with healthy patterns (P > 0.1). A similar interaction effect was observed using longitudinal data (Pinteraction = 0.029). These findings highlight a novel gene-diet interaction on the susceptibility to cardiometabolic disorders, which has a long-term impact from childhood onward, particularly in those with normal weight. Personalized dietary advice in these individuals may be recommended as an early possible therapeutic measure to improve metabolic health.


Govert Bidloo (1649-1713) and the first description of lipomyelomeningocele.
Govert Bidloo was a Dutch anatomist and royal physician who lived during the sixteenth and seventeenth centuries. Most remembered for his anatomy text and feud with contemporary William Cowper, Bidloo's surgical text appears to describe the first case of what is now known as a lipomyelomeningocele. The authors review the life of Bidloo and his description of this pathologic entity. Govert Bidloo appears to have described a lipomyelomeningocele almost 200 years before the description often mentioned as the sentinel paper on this topic.


Trauma-induced vestibular dysfunction: Possible functional repair under α1-antitrypsin-rich conditions.
Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthotomy in wild-type mice and in mice overexpressing human AAT. A 2-week-long assessment of vestibular signs followed. All animals responded with peak vestibular dysfunction scores within 4 h after local trauma. While wild-type animals displayed partial or no recovery across 7 days post-injury, AAT-rich group exhibited early recovery: from behavioral score 9-out-of-9 at peak to 4.8 ± 0.44 (mean ± SD) within 8 h from injury, a time when wild-type mice scored 8.6 ± 0.54 (p < 0.0001), and from vestibular score 15-out-of-15 to 7.8 ± 2.2 within 24 h, when wild-type mice scored 13.0 ± 2.0 (p < 0.01). Thus, recovery and functional normalisation of an injured vestibular compartment is achievable without corticosteroid therapy; expedited tissue repair processes appear to result from elevated circulating AAT levels. This study lays the foundation for exploring the molecular and cellular mediators of AAT within the repair processes of the delicate microscopic structures of the vestibular end organ.


Candicidin in treatment of benign prostatic hypertrophy.
In a prospective, double-blind, placebo-controlled multicenter study, candicidin (a polyene macrolide) was investigated in the treatment of benign prostatic hypertrophy. Seventy-six patients were included in the study--34 in the candicidin group and 42 in the placebo group. Patients treated with 270 mg. of candicidin daily for 6 months had a significant decrease in residual urine, voided volume and bladder volume. No significant increases were found in flow rates. Symptoms improved significantly in both the candicidin and the placebo group, but no differences in improvement were found between the groups. The results of candicidin treatment are less satisfactory than those following surgery.


Physical-Chemical Crosslinked Electrospun Colocasia esculenta Tuber Protein-Chitosan-Poly(Ethylene Oxide) Nanofibers with Antibacterial Activity and Cytocompatibility.
Electrospun nanofibers based on Colocasia esculenta tuber (CET) protein are considered as a promising material for wound dressing applications. However, the use of these nanofibers in aqueous conditions has poor stability. The present study was performed to obtain insights into the crosslinked electrospun CET's protein-chitosan (CS)-poly(ethylene oxide) (PEO) nanofibers and to evaluate their potential for wound dressing applications. The electrospun nanofibers were crosslinked with glutaraldehyde (GA) vapor and heat treatment (HT) to enhance their physicochemical stability. The crosslinked nanofibers were characterized by protein profiles, morphology structures, thermal behavior, mechanical properties, and degradation behavior. Furthermore, the antibacterial properties and cytocompatibility were analyzed by antibacterial assessment and cell proliferation. The protein profiles of the electrospun CET's protein-CS-PEO nanofibers before and after HT crosslinking contained one major bioactive protein with a molecular weight of 14.4 kDa. Scanning electron microscopy images of the crosslinked nanofibers indicated preservation of the structure after immersion in phosphate buffered saline. The crosslinked nanofibers resulted in higher ultimate tensile strength and lower ultimate strain compared to the non-crosslinked nanofibers. GA vapor crosslinking showed higher water stability compared to HT crosslinking. The in vitro antibacterial activity of the crosslinked nanofibers showed a stronger bacteriostatic effect on Staphylococcus aureus than on Escherichia coli. Human skin fibroblast cell proliferation on crosslinked GA vapor and HT nanofibers with 1% (w/v) CS and 2% (w/v) CET's protein demonstrated the highest among all the other crosslinked nanofibers after seven days of cell culture. Cell proliferation and cell morphology results revealed that introducing higher CET's protein concentration on crosslinked nanofibers could increase cell proliferation of the crosslinked nanofibers. These results are promising for the potential use of the crosslinked electrospun CET's protein-CS-PEO nanofibers as bioactive wound dressing materials.


Pruritus as a presenting sign of acquired immunodeficiency syndrome.
A 65-year-old man with insulin-dependent diabetes developed intractable pruritus preceding weight loss and increasing fatiguability. Esophagogastroduodenoscopy revealed infection with Candida, cytomegalovirus, and Cryptosporidium. His T cell helper/suppressor ratio was inverted, and the serum human immunodeficiency virus (HIV) antibody was positive. Results of an extensive evaluation for internal malignancy were negative. Despite optimal care, the patient died 12 weeks after his initial hospitalization. We believe that HIV infection should be added to the list of underlying disorders that may present with pruritus.


[Rare diseases with clinical relevance-the Silver-Russell syndrome].
The Silver-Russell syndrome (SRS) is a rare imprinting disease associated with pre- and postnatal growth retardation, craniofacial features, and asymmetry. Genitourinary abnormalities are seen in up to 20% of affected individuals. Apart from structural renal anomalies, cryptorchidism and hypospadias occur frequently in boys, while girls often have anomalies similar to those in Mayer-Rokitansky-Küster-Hauser syndrome with congenital hypoplasia or aplasia of the uterus and upper part of the vagina. Frequently hypospadias repair and orchiopexy are difficult because of lack of buccal mucosa due to facial dysmorphism and intraabdominal position of the testicles, respectively. Anesthetic problems with SRS children can be profound and mostly concern a difficult airway due to facial dysmorphism. Especially the young, very thin SRS patients are prone to hypoglycemia and hypothermia and require close perioperative monitoring. Children with SRS and their families face challenges from birth to adulthood. In case of urogenital abnormalities, they should receive multidisciplinary care by pediatric urologists/surgeons and pediatric anesthesiologists in a center of expertise in rare diseases.


Comparative study of NK cell-mediated cytotoxicity using radioactive and flow cytometric cytotoxicity assays.
Cell-mediated cytotoxicity is a major effector pathway of the immune system. Thus far, radioactive assays have been widely used, but have significant disadvantages. Meanwhile, flow cytometric assays have been established but have not all been assessed simultaneously relative to the radioactive assays. Here, we have evaluated flow cytometric enumeration of surviving target cells, annexin-V binding and detection of activated caspase-3 and caspase-6 in direct comparison to the 51chromium (51Cr) release assay, and the JAM test. For assay evaluation NKL effector cells Fas-resistant K562 and Fas-sensitive Jurkat target cells were studied. Percent specific lysis measured for each E:T ratio was fitted to a sigmoid dose response curve. Both the flow cytometric and radioactive cytotoxicity assays showed equivalent background lysis (1-13%) but differed considerably with respect to maximum cytotoxicity (11-82% in K562 and 49-75% in Jurkat cells). Half maximum lysis ranged from 4:1 to 28:1 E:T ratios in K562 cells and from 1:3 to 24:1 in Jurkat cells, respectively. Flow cytometric enumeration of surviving target cells was the only assay which permitted detection of cytotoxicity at considerable lower E:T ratios (in K562 cells 1:4 to 2:1 and in Jurkat cells 1:4 to 1:1) than the conventional assays. Prolonged incubation over 24 h did not improve the sensitivity for flow cytometric enumeration of surviving target cells or the JAM test. The observed differences in the lysis of target cells are likely to reflect different sensitivity of cell death-associated changes which are measured by each assay. Thus, the particular choice of a cytotoxicity assay must be carefully adapted to the experimental situation under study.


Socioeconomic determinants of long sickness absence affected by work, family, and personal health-related characteristics: A longitudinal study of the Japanese civil servants.
Sickness absence is increasingly affecting society at different levels. This study explores how work, family, and personal health-related characteristics will contribute to socioeconomic status (SES) differences in future long sickness absence (7 days or more) with respect to sex differences. A total of 1562 civil servants worked for the Local Japanese government and were considered from 2003 to 2014 for this study. Logistic regression analyses were performed to examine whether there were employment-grade differences in long sickness absence after 11 years and whether such SES differences were associated with work, family, and personal health-related characteristics or sexes. Male low-grade employees had a significantly higher odds ratio (OR) for long sickness absence (age-adjusted OR = 1.75, 95% confidence interval (CI) [1.04-2.95]). However, after adjustment for work characteristics, the association of significance disappeared (OR = 1.65, [0.96-2.84]). Female low-grade employees had a significantly lower OR for long sickness absence after 11 years (OR = 0.26, [0.08-0.86]). Male employees working long hours and male and female employees in high job demand take less sickness absence. Meanwhile, male employees working short hours take longer sickness absence. This study showed that male employees at low grades take longer sickness absence than those at high grades; however, this was alleviated by work characteristics. Female employees at low grades take less sickness absence than those at high grades. Japanese female employees with low grades, male employees with long working hours, and both sexes with high job demands take less sickness absence, although they may be unhealthy because of work stress.


A case of galactorrhea during paroxetine treatment.
Paroxetine is one of the selective serotonin reuptake inhibitor antidepressant drugs. Galactorrhea can be seen during antidepressant treatments. There are a few reports in literature on paroxetine use and related prolactin level changes. We present a case that was receiving paroxetine in whom despite low blood levels of the drug, hyperprolactinemia, and galactorrhea was found. We present a case that was receiving paroxetine despite low drug blood levels, hyperprolactinemia, and galactorrhea was found in this article.


X-linked agammaglobulinemia--gene cloning and future prospects.
The btk gene has recently been identified as the causative gene in X-linked agammaglobulinemia (XLA). This has opened up many new possibilities for the treatment of this B-cell immunodeficiency. Christine Kinnon and colleagues review the high degree of sequence of homology of btk to the non-receptor tyrosine kinases and speculate on putative roles for this gene in B-cell development.


Involvement of brain serotonergic system in the antinociceptive action of acetylsalicylic acid in the rat.
The pain-threshold in the hot-plate test and serotonin (5-HT) receptor binding capacity in the cortex and pontine areas of rat brain were studied after intraperitoneal (ip) administration of acetyl salicylate of lysine equivalent to 400 mg/kg of acetylsalicylic acid (ASA). The antinociceptive activity of ASA was prevented by ip pre-treatment with Parachlorophenylalanine (PCPA) at the rate of 100 mg/kg/day for 4 days. PCPA pre-treatment increased the number of 5-HT receptors and abolished the ASA-induced reduction in 5-HT receptor binding capacity in the cortex but did not affect serum salicylate levels. These results provide support for the hypothesis that the antinociceptive action of ASA, at least in the hot-plate test, involves the central serotonergic system.


Biosynthesis, isolation, purification and seperation of Zearalenone, deoxynivalenol and 15-Acetyldeoxynivalenol.
Fusarium graminearum KF-376 isolate was found to be able to form simultaneously three toxic metabolites: zearalenone (FF-2), deoxynivalenol (DON) and 15-acetyldeoxynivalenol (15-AcDON). Toxins were extracted with methanol - water 3:1 (v/v) and purified by liquid chromatography on charcoal - Kieselgel 60 column (preliminary) and Aluminiumoxid 90 column. Final separation of the metabolites was achived on Kieselgel 60 - Aluminiumoxid 90 column.


[Ochratoxin a analyses of blood samples from workers at waste handling facilities].
Tasks such as manual sorting of domestic wastes for recyclable goods and the deposition of various materials may result in inhalation of mycotoxin-containing aerosols. Ochratoxin A (OTA) was analyzed in blood samples from workers employed at waste handling facilities in Southern Germany to assess the potential impact of this mycotoxin, and explore its use as a biomarker of exposure to bioaerosols. Results from this analysis are reported: OTA serum levels (median values) in subgroups of workers involved in waste deposition (n=76 'Deponierer') or in waste sorting (n=60 'Wertstoffsortierer') were 0.36 and 0.53 ng/ml, respectively. Both groups are natives of countries within the European Community (EU). In waste sorters who were born in other European (non-EU) countries (n=72) or elsewhere (n=12 from Asia, Africa), the OTA serum levels were 0.50 and 0.37 ng/ml, respectively. In controls (n=84 office clerks at the facilities; EU citizens) the median OTA value was 0.39 ng/ml. Comparing the different groups, and previously published data on median OTA levels in the general population (0.21 ng/ml) which result from dietary (background) exposure to OTA in Germany, our data point to an additional uptake of this mycotoxin by inhalation in workers with exposure to bioaerosols. The results support the view that apart from the pathogenic and allergological relevance of microbial emissions from garbage, secondary fungal metabolites, and thus toxicological aspects, deserve further attention.


MR-guided percutaneous ethanol injection for hepatocellular carcinoma in a 0.2T open MR system.
The purpose of this work is to describe our experience with single-session percutaneous ethanol injection (PEI) under the guidance of 0.2-T open MRI for hepatocellular carcinomas (HCC) that were not suitable for ablation under ultrasound (US) or computed tomography (CT) guidance. None of the lesions (N = 7) were detectable on US. MRI was chosen over CT as the guidance modality because the nodules were located in the hepatic dome (N = 4) or were invisible on noncontrast CT (N = 3). All of the nodules were targeted successfully, and apparently complete tumor necrosis was achieved in six nodules (86%). During a follow-up of one to 41 months, only one patient developed local recurrence four months after PEI. MR-guided PEI is feasible and effective for treating HCC when other imaging guidance methods are not appropriate.


Intrauterine exposure to hypertensive disorders of pregnancy and postnatal growth in extremely and very preterm infants.
There is growing evidence regarding the association between rapid growth during infancy and metabolic and cardiovascular diseases later in life. We aimed to evaluate postnatal growth trajectories in extremely and very preterm infants exposed to hypertensive disorders of pregnancy (HDP) in utero. This multicenter retrospective study used a nationwide database of preterm infants weighing ≤1,500 g born between 22 and 31 weeks of gestation between 2003 and 2015. The Z-scores for height and weight were evaluated at three time points (at birth, corrected age of 1.5 years, and chronological age of 3 years) in 5,144 infants (HDP, n = 1,188; non-HDP, n = 3,956). Univariate and multivariate regression analyses were performed to investigate the associations between HDP exposure and accelerated postnatal growth. Male and female infants in the HDP group showed increased mean Z-scores for height and weight, whereas those in the non-HDP group showed decreased mean Z-scores. Multivariate analyses showed that HDP were associated with accelerated postnatal growth (Δ Z-scores) in weight in both male and female infants (β coefficient [95% CI]; male 0.17 [0.05-0.30], female 0.27 [0.14-0.39]), but not in height (male 0.02 [-0.09 to 0.13], female 0.04 [-0.06 to 0.15]). An interaction analysis revealed no significant differences in the effects of HDP on postnatal growth between male and female infants. Intrauterine exposure to HDP contributes to accelerated postnatal weight growth in extremely and very preterm infants during early childhood. In addition, no sex differences were observed in postnatal growth.


Dealing with initial inconclusive serological results for chronic Chagas disease in clinical practice.
Most guidelines for Chagas disease recommend the performance of two serological tests in order to detect it. However, inconclusive results may arise from this strategy. The aim was to describe whether serological follow-up together with the patient's clinical characteristics could clarify the outcome of patients with initial inconclusive test results. In this retrospective case series, all results of Chagas disease serological tests and outpatient visits recorded from 2004 to 2008 were screened for inclusion. The inclusion criterion was clinical suspicion of chronic Chagas disease and the exclusion criteria were previous diagnosis of Chagas disease, suspicion of acute Chagas disease, and serological tests with no corresponding medical evaluation. A total of 1,732 patients were analyzed. Chronic Chagas disease prevalence was 21.1%. After the initial set of serological tests, 2.9% of patients had inconclusive test results. Most of these patients had definite diagnosis after clinical follow-up and the repetition of serological tests in a new blood sample. Loss to follow-up while partaking in the diagnostic investigation reached 17.7%. The prevalence of initial inconclusive serological tests for chronic Chagas disease is low. Clinical evaluations and follow-up clarify the definite diagnosis. Noncompliance to follow-up is a frequent problem. Strategies to reduce inconclusive results and noncompliance are discussed.


Tretinoin for the treatment of cutaneous graft-versus-host disease.
Chronic graft-versus-host disease (GVHD) of the skin is a common complication of allogeneic bone marrow transplantation. It can be resistant to common methods of systemic immunosuppression. We report successful treatment of a patient with progressive cutaneous GVHD that was resistant to cyclosporine and steroids after allogeneic marrow transplantation for acute myelogenous leukemia using topical tretinoin (Retin-A).


Immune response to Bordetella pertussis is associated with season and undernutrition in Senegalese children.
While vaccines elicit a protective response in most recipients, studies suggest that environmental and nutritional factors can influence the strength of the individual response to immunization and to subsequent natural infectious challenges. We conducted a longitudinal survey in Senegal to assess the individual response to B. pertussis, a respiratory disease against which Senegalese children are vaccinated before the age of one (Clinicaltrials.gov ID: NCT01545115). A cohort of 203 children aged 1-9 from four villages of the Senegal River Valley was followed-up for 14 months (October 2008-January 2010). During that period, four visits have been made to the villages to assess the immunological and nutritional status of these children and to determine risk factors involved in the modulation of their humoral immune response to B. pertussis toxin. A multivariate model has demonstrated that birth season and nutritional status appeared to modulate humoral response to pertussis toxin. Moreover, response to B. pertussis was dependent on age, village and time of visit. These results are consistent with the hypothesis that environmental and nutritional factors modulate children's response to pertussis following natural infection or vaccination.


Emergency Focused Assessment with Sonography in Blunt Trauma Abdomen.
Focused assessment with sonography in trauma (FAST) being a rapid noninvasive examination is used primarily to evaluate for the evidence of traumatic free fluid suggestive of injury in the peritoneal, pericardial, and pleural cavities. It is widely recognized as a mainstream emergency skill in the management of trauma. The aim of the study is to evaluate the accuracy of FAST in patients presenting with blunt abdominal trauma. Data were collected prospectively from FAST scans conducted in blunt trauma abdomen (BTA) patients. Positive and negative FAST scans were confirmed either with contrast-enhanced computed tomography (CECT) abdomen or with exploratory laparotomy, thus dividing it further into four groups, i.e., true-positive, false-positive, true-negative, and false-negative scans. After collecting the data, accuracy of FAST was calculated. In this study, a total of 104 patients were included. The mean age was 38.17 years. Most common cause of BTA was road traffic accident. The overall sensitivity, specificity, and accuracy of FAST were 69.8%, 92.1%, and 80.8%, respectively. This study showed that FAST is of paramount importance in patients who are hemodynamically unstable as it has a high positive predictive value. However, a FAST-negative result should always be confirmed by other modalities.


Direct detection of Epstein-Barr virus DNA from a single Reed-Sternberg cell of Hodgkin's disease by polymerase chain reaction.
Eleven cases of Hodgkin's disease (HD) were examined for the presence of the Epstein-Barr virus (EBV) genome, using the polymerase chain reaction (PCR) to detect EBV DNA in whole paraffin-embedded tissue specimens and in single cells picked out from the specimens with a micromanipulator. The EBV genome was detected in 5 of the 11 cases by conventional PCR. Single cell PCR demonstrated the EBV genome in Reed-Sternberg cells from all the EBV-positive cases, but not from any of the EBV-negative cases. Background lymphocytes and lysozyme-positive histiocytes from EBV-positive cases did not contain the EBV genome. These results indicate an etiological association of EBV with some cases of HD.


Trypsin-modified alkaline phosphatase. Formation of apoenzyme monomer and hybrid dimer.
The cleavage of an amino-terminal decapeptide from Escherichia coli alkaline phosphatase has been previously described (Roberts, C. H., and Chlebowski, J. F. (1984) J. Biol. Chem. 259, 729-733) by this laboratory. The modest reduction in specific activity of the modified enzyme is paralleled by an apparent alteration in the Zn(II) affinity at one of the three active center metal ion binding sites. In contrast to the behavior of the native enzyme, formation of the metal-free apoprotein results in an irreversible loss of catalytic activity; phosphohydrolase activity is not restored on addition of Zn(II) and Mg(II). Differential scanning calorimetry and velocity sedimentation data indicate that the apo form of the modified enzyme exists as a monomer form which, while capable of binding Zn(II) does not readily reassociate to active dimer. Processive cleavage of the amino termini of the dimer by trypsin results in the transient formation of a hybrid dimer consisting of cleaved and uncleaved subunits. This species can be directly observed and isolated by taking advantage of the differential chromatographic mobility of the native "isozymes" and the resulting products. Coupled with improved procedures for the preparation of the modified protein, these data indicate that the amino-terminal modification results in alterations in the subunit interface domain and provides a species (the hybrid dimer) for the investigation of the propagation of these effects.


Dietary wheat gluten induces astro- and microgliosis in the hypothalamus of male mice.
Gluten, which is found in cereals such as wheat, rye and barley, makes up a major dietary component in most western nations, and has been shown to promote body mass gain and peripheral inflammation in mice. In the current study, we investigated the impact of gluten on central inflammation that is typically associated with diet-induced obesity. While we found no effect of gluten when added to a low-fat diet (LFD), male mice fed high fat diet (HFD) enriched with gluten increased body mass and adiposity compared with mice fed HFD without gluten. We furthermore found that gluten, when added to the LFD, increases circulating C-reactive protein levels. Gluten regardless of whether it was added to LFD or HFD led to a profound increase in the number of microglia and astrocytes in the arcuate nucleus of the hypothalamus, as detected by immunohistochemistry for ionised calcium binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), respectively. In mice fed LFD, gluten mimicked the immunogenic effects of HFD exposure and when added to HFD led to a further increase in the number of immunoreactive cells. Taken together, our results confirm a moderate obesogenic effect of gluten when fed to mice exposed to HFD and for the first-time report gluten-induced astro- and microgliosis suggesting the development of hypothalamic injury in rodents.


Management of low back pain in primary care prior to multidisciplinary functional restoration: a retrospective study of 72 patients.
Chronic low back pain is a major socioeconomic health issue, due to the high direct (healthcare) and indirect (sick leave) costs. The aim of the present study was to describe the primary care management of low back pain patients prior to their inclusion in a multidisciplinary functional restoration network. A descriptive, retrospective, questionnaire-based survey of the general practitioners dealing with 72 low back pain patients. Patients had been monitored by their general practitioner for an average of four years, with a mean frequency of eight appointments per year per patient. Ninety-three percent and 60% of the patients had been referred to a rheumatologist and a surgeon, respectively. Ninety-eight percent had had lumbar radiographies, 80% had undergone a computed tomography scan and 64% had undergone magnetic resonance imaging. The most commonly prescribed medications were anti-inflammatories and first- or second-line analgesics. Thirty percent had already received morphine analgesics and 50% had taken antidepressants. Thirty-two percent had undergone lumbar surgery. Physiotherapy was frequently reported and, indeed, 6% of patients had participated in over 100 sessions. Total sick leave averaged 8.25 months over the study's follow-up period. The time interval before referral to a multidisciplinary care team is long and so GPs should be encouraged and helped to organize this process earlier. It is also essential to determine factors which predict progression to chronic LBP.


Efficient conversion of mannitol derived from brown seaweed to fructose for fermentation with a thraustochytrid.
Macroalgae are a promising biomass feedstock for energy and valuable chemicals. Mannitol and alginate are the major carbohydrates found in the microalga Laminaria japonica (Konbu). To convert mannitol to fructose for its utilization as a carbon source in mannitol non-assimilating bacteria, a psychrophile-based simple biocatalyst (PSCat) was constructed using a psychrophile as a host by expressing mesophilic enzymes, including mannitol 2-dehydrogenase for mannitol oxidation, and NADH oxidase and alkyl hydroxyperoxide reductase for NAD+ regeneration. PSCat was treated at 40 °C to inactivate the psychrophilic enzymes responsible for byproduct formation and to increase the membrane permeability of the substrate. PSCat efficiently converted mannitol to fructose with high conversion yield without additional input of NAD+. Konbu extract containing mannitol was converted to fructose with hydroperoxide scavenging, inhibiting the mannitol dehydrogenase activity. Auranthiochytrium sp. could grow well in the presence of fructose converted by PSCat. Thus, PSCat is a potential carbohydrate converter for mannitol non-assimilating microorganism.


Role of Endoscopy in Resection of Intracanalicular Vestibular Schwannoma via Middle Fossa Approach: Technical Nuances.
Surgical resection of vestibular schwannomas (VS) located within the internal auditory canal (IAC) is challenging, especially those located very laterally in the IAC. Various transcranial approaches have been described for resection of intracanalicular VS including retrosigmoid, translabyrinthine, and middle fossa approaches. Each approach has its indications, advantages, and limitations. The middle fossa approach (MFA) is considered by many authors as the gold standard approach for resection of small intracanalicular VS in young patients with serviceable hearing; however, there is often a limitation in complete visualization of the tumor. The authors present an illustrative case to highlight the technical nuances of complementary use of endoscopy in MFA for complete resection of intracanalicular VS located at the IAC fundus, preserving preoperative hearing status and mainting intact facial nerve function. In our experience, the combined use of the endoscope and the microspe as described here and illustrated in our case, improves visualization of the IAC and its contents, improving ressection and outcomes. MFA allows for a direct yet safe surgical corridor to small intracanalicular VS. The implementation of endoscopy with MFA, especially for VS located laterally in the IAC, allows for better opportunity for complete resection of the tumor with improved preservation of hearing and facial nerve function.


Distinct differences in the pattern of hemodynamic response to happy and angry facial expressions in infants--a near-infrared spectroscopic study.
Recognition of other people's facial expressions of emotion plays an important role in social communication in infants as well as adults. Evidence from behavioral studies has demonstrated that the ability to recognize facial expressions develops by 6 to 7 months of age. Although the regions of the infant brain involved in processing facial expressions have not been investigated, neuroimaging studies in adults have revealed that several areas including the superior temporal sulcus (STS) participate in the processing of facial expressions. To examine whether the temporal area overlying the STS is responsible for the processing of facial expressions in infants, near-infrared spectroscopy (NIRS) was used to measure the neural activity in the temporal area overlying the STS as infants looked at happy and angry faces. NIRS provides a non-invasive means of estimating cerebral blood flow in the human brain and does not require severe constraints of head-movement. According to the International 10-20 system for EEG electrode placement, the measurement area was located in the bilateral temporal area centered at positions T5 and T6, which correspond to the STS. The time-course of the average change in total-Hb concentration revealed a clear difference in the pattern of hemodynamic responses to happy and angry faces. The hemodynamic response increased gradually when infants looked at happy faces and was activated continuously even after the disappearance of the face. In contrast, the hemodynamic responses for angry faces increased during the presentation of angry faces, then decreased rapidly after the face disappeared. Moreover, the left temporal area was significantly activated relative to the baseline when infants looked at happy faces, while the right temporal area was significantly activated for angry faces. These findings suggest hemispheric differences in temporal areas during the processing of positive and negative facial expressions in infants.


Pregnancy complicated with pulmonary edema due to hyperthyroidism.
Hyperthyroidism is one of the most common causes of cardiac failure. Blood volume expands greatly during pregnancy, especially after the last part of the second trimester. Such expansion exacerbates the symptoms of heart failure and accelerates the development of pulmonary edema when abnormal thyroid function is not well controlled. Two cases of pregnancy complicated with congestive heart failure and pulmonary edema due to hyperthyroidism are reported here. Both patients did not receive treatment for hyperthyroidism during pregnancy, and both sought clinical help during the third trimester. The clinical problems were resolved by medical management before delivery.


Preliminary X-ray diffraction analysis of crystals of Bacillus thuringiensis toxin, a cell membrane disrupting protein.
Crystals suitable for high resolution X-ray diffraction analysis have been reproducibly grown of the 24,000 Mr protein insect toxin from Bacillus thuringiensis. This protein, which demonstrates substantial insecticidal activity by inserting into phospholipid membranes, crystallizes as long square needles from polyethylene glycol 4000 at neutral pH. The crystals are of space group P4(1) and have cell dimensions of a = b = 33 A and c = 235 A, which suggests to us a predominantly helical motif for the protein's structure.


Antioxidant and anti-inflammatory activities of Centratherum anthelminticum (L.) Kuntze seed oil in diabetic nephropathy via modulation of Nrf-2/HO-1 and NF-κB pathway.
Type 2 diabetes mellitus (T2DM) approximately constitutes 90% of the reported cases. 30-40% of diabetics eventually develop diabetic nephropathy (DN); accounting for one of the major causes of morbidity and mortality. Increased glucose autoxidation and non-enzymatic glycation of proteins in diabetic kidneys lead to the excessive generation of reactive oxygen species (ROS) that results in lipid peroxidation and activation of inflammatory mediators which overwhelms the scavenging capacity of the antioxidant defense system (Nrf2/Keap1/HO-1). Centratherum anthelminticum commonly called as kali zeeri (bitter cumin) and its seeds are well known for culinary purposes in Asia (Pakistan). It has reported anti-inflammatory, antioxidant, and anti-diabetic activities. The present study has attempted to explore the in-vivo anti-inflammatory, antioxidant and antihyperglycemic potential of the C. anthelminticum seed's fixed oil (FO) and its fractions in high fat-high fructose-streptozotocin (HF-HFr-STZ) induced T2DM rat model. The T2DM rat model was developed by giving a high-fat and high-fructose diet followed by a single intraperitoneal injection of streptozotocin (STZ 60 mg/kg) on 28th day of the trial. After 72 hours of this injection, rats showing fasting blood glucose (FBG) levels≥230 mg/dL were recruited into six groups. These groups were orally administered distilled water (1 mL/kg), Gliclazide (200 mg/kg), Centratherum anthelminticum seed (FO) and its hexane (HF), chloroform (CF) and ethanol (EF) soluble fractions (200 mg/kg each), respectively for 4 weeks (i.e. 28 days). Blood, serum, and kidney tissue samples of euthanized animals were used for biochemical, pro-inflammatory, and antioxidant markers (ELISA, qRT-PCR, and spectrophotometric assays) and histology, respectively. C. anthelminticum FO and its fractions reduced the lipid peroxidation, and improved the antioxidant parameters: enzymatic (SOD, CAT, and GPx), non-enzymatic (GSH), and mRNA expression of anti-inflammatory markers (Nrf-2, keap1, and HO-1). mRNA expression of inflammatory and apoptotic markers (TNF-α, IL-1β, COX-1, NF-κB, Bax, and Bcl-2) were attenuated along with improved kidney architecture. C. anthelminticum can mitigate inflammation and oxidative stress in early DN. The anti-nephropathic effect can be attributed to its ability to down-regulate NF-κB and by bringing the Nrf-2 expression levels to near normal.


Polymorphism within the distal RAD51 gene promoter is associated with colorectal cancer in a Polish population.
Colorectal cancer (CRC) is one of the most common cancers in developed countries. Annually, over one million of new cases in the world are recorded. Majority of CRCs occur sporadically with dominant phenotype of chromosomal instability (CIN). Permanent exposure to DNA damaging agents such as ionizing radiation result in DNA double-stranded breaks, which create favorable conditions for chromosomal aberration to arise. Homologous recombination repair (HRR) is the leading process engaged in maintaining of the genome integrity. RAD51 protein was recognized as crucial in HRR. Single nucleotide polymorphisms are the primary source of genetic variation which presence in the RAD51 promoter region can affect on its expression and consequently modulate HR efficiency. The aim of this study was to analyze the distribution of genotypes and allele frequencies of -4791A/T and -4601A/G RAD51 gene polymorphisms, followed by an assessment of their relationship with the risk of CRC. The study included 115 patients with confirmed CRC. Control group was consisted of 118 cancer-free individuals with a negative family history. The genotypes were identified by PCR-RFLP method. This study revealed statistically significant association between appearance of G/A genotype in position -4601 of RAD51 gene and CRC risk.


Sonographic Parameters Predicting the Outcome of Patients With Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Treated With Alpha1-Adrenoreceptor Antagonist.
To define prostate and bladder sono-morphologic parameters that best predict the outcome of benign prostatic hyperplasia (BPH) in men treated with alpha1-adrenoreceptor antagonist. Patients with BPH, candidates for medical treatment, were prospectively enrolled. Besides basic evaluation measures, all patients underwent transrectal ultrasonography. The main outcome was the response to treatment on the basis of International Prostatic Symptom Score, quality of life score, and maximum urine flow rate after taking daily oral dose of tamsulosin 0.4 mg for 6 months. The influences of baseline parameters on treatment response were statistically analyzed. A total of 166 patients completed the study. From these, 59 (35.5%) had ineffective treatment after 6 months. According to logistic regression analysis, baseline International Prostatic Symptom Score storage subscore, maximum urine flow rate, and transrectal ultrasonography-measured sono-morphologic parameters (bladder wall thickness [BWT], ultrasound estimated bladder weight [UEBW], and intravesical prostatic protrusion [IPP]) were the independent predictors of ineffective treatment (P < .05). Using receiver operating characteristics analysis, BWT, UEBW, and IPP had adequate area under the curve (0.939, 0.897, and 0.876, respectively). At cutoff values of 9.3 mm, 34.5 g, and 12.9 mm, the positive and negative predictive values for BWT, UEBW, and IPP were 83.6% and 92.4%; 78.2% and 85.6%; 80.3% and 90.5%; respectively. Combination of these sono-morphologic parameters increased their positive predictive value to 97.6%. Sonographic measurements of BWT, UEBW, and IPP might aid in determining patients with BPH at high risk of alpha1-adrenoreceptor antagonist monotherapy failure, in turn determining the initial need for additional medical therapy or surgical intervention.


Preservation of fecal glucocorticoid metabolites and immunoglobulin A through silica gel drying for field studies in horses.
Non-invasive methods enable stress evaluation through measuring fecal glucocorticoid metabolites (FGMs), and immunoglobulin A (IgA) in the feces avoiding stressful blood drawing or stressful restraining of animals in the field. However, FGMs and IgA are mostly analysed in freshly frozen samples, which is difficult when fresh samples cannot be frozen immediately or frozen samples cannot be stored or transported. Good results were also derived from air-dried fecal samples, which are hampered by unstable air humidity in the field. These difficulties may be overcome, when drying of samples could be induced with colorless silica gel (SiO2) granules in a secure set-up, such as an air tight tube. We determined the speed of drying 1.5 g of a fresh fecal sample from six horses on air and on silica gel. Furthermore, FGMs and IgA were analysed in differently stored subsamples from 12 horses: in frozen fecal samples, in air- or silica gel-dried samples stored for 1 day and for 7 days, and in wet fecal samples kept in a tube at room temperature for 7 days. FGM levels remained stable in feces dried on air or on silica gel for 7 days, whereas IgA quantities showed a significant loss. Under field conditions, when freezing or transporting the frozen samples is not possible and humidity hampers air drying, drying samples on silica gel in air tight tubes appears to be very helpful and reliable for analysing FGMs.


Effect of Integrated Gastroenterology Specialists in a Primary Care Setting: a Retrospective Cohort Study.
Gastrointestinal (GI) complaints are common in primary care practices. The patient-centered medical home (PCMH) may improve coordination and collaboration by facilitating coordination across healthcare settings and within the community, enhancing communication between providers, and focusing on quality of care delivery. To investigate the effect of integrated community gastroenterology specialists (ICS-GI) model within a large primary care practice. Retrospective cohort with propensity-matched historic controls. We identified 265 patients who had a visit with one of our ICS-GI specialists and matched them (1:2) to 530 similar patients seen prior to the implementation of the ICS-GI model. Frequency of diagnostic testing for GI indications, visits to our outpatient GI referral practice, emergency department and hospital utilization, and time to access of specialty care for the whole population and by GI condition group. Patients seen in our ICS-GI model had similar outpatient care utilization (OR = 1.0, 95% CI 0.7-1.4, p = 0.90), were more likely to have visits in primary care (OR OR=1.5, 95% CI 1.1-2.2, p = 0.02), and were less likely to have visits to our GI outpatient referral practice (OR = 0.3, 95% CI 0.2-0.7, p < 0.0001). Condition-specific analyses show that all GI conditions experienced decreased visits to the outpatient GI referral practice outside of patients with GI neoplasm. Populations did not differ in emergency department, hospital, or diagnostic utilization. We observed that an embedded specialist in primary care model is associated with improved care coordination without compromising patient safety. The PCMH could be extended to include subspecialty care.


Effects of astrocytes and microglia on neuroinflammation after spinal cord injury and related immunomodulatory strategies.
Spinal cord injury (SCI) is a catastrophic event which is still without adequate therapies. Neuroinflammation is the main pathogenesis of secondary damage post-SCI, leading to tissue loss and neurological dysfunction. Previous studies have shown that microglia and astrocytes are the major immune cells in the central nervous system (CNS) and play a crucial role in modulating neuroinflammatory responses. In this study, we mainly review the effects of neuroinflammation in SCI, focusing on the contributions of microglia and astrocytes and their cross-talk. Furthermore, we will also discuss therapeutic strategies on how to regulate their immunophenotype to suppress robust inflammation and facilitate injury prognosis.


A flexible paper based electrochemical portable biosensor towards recognition of ractopamine as animal feed additive: Low cost diagnostic tool towards food analysis using aptasensor technology.
Due to the costly and time-consuming traditional techniques, providing a low-cost, portability and flexibility diagnostic tool with the ability to monitor and detect various animal feed additive is highly demanded. Over the years, paper-based biosensors have emerged as point of care (POC) diagnostic, easy-to-use and miniaturized tools. However, they have been suffered from low sensitivity. Aptamer as appropriate bioreceptor can overcome the most common disadvantage of paper based sensor by increasing selectivity and sensitivity. In this study, a novel paper-based electrochemical aptasensor was successfully developed to detection of ractopamine (RAC). RAC concentration was evaluated using a designed three-electrode paper based biodevice system. Under the optimal experimental conditions, the engineered aptasensor provided good sensitivity and selectivity for the detection of RAC. Using proposed flexible sensor RAC was determined in the range of 0.001 µM to 100 mM which the lower limit of quantitation (LLOQ) was obtained as 0.01 µM. Finally, aptasensor was used to the monitoring of RAC in untreated human plasma specimens which LLOQ and linear range were 0.01 µM and 0.01 µM to 10 mM, respectively. We hope that the exploitation of aptamer in electrochemical paper based sensor will be able to broaden our understanding for developing the application of low-cost and portable biodevices for the sensitive and selective paper-based sensor to identify other chemical and biological compounds.


Hyperoside alleviates postmenopausal osteoporosis via regulating miR-19a-5p/IL-17A axis.
Postmenopausal osteoporosis (PMO) is a common osteoporosis. Hyperoside (Hyp), a natural flavonoid compound, has anti-osteoporotic effects, but the underlying mechanisms remain poorly understood. Inflammatory cytokine IL-17A is upregulated in PMO and plays vital roles in bone loss, but the upstream regulatory factors and mechanisms are still unknown. Twenty PMO patients and 20 healthy control subjects were included to analyze IL-17A expression changes and screen dys-regulated miRNAs in the peripheral blood of PMO patients. miR-19a-5p mimics and inhibitor were transfected into RAW264.7 osteoclasts, and injected into bilateral ovariectomized (OVX) mice to explore the regulatory effect of miR-19a-5p on IL-17A. OVX mice were randomly grouped and treated with different doses of Hyp to uncover the effective targets for the medicine in PMO disease. MiR-19a-5p was downregulated in PMO patients and the expression level was negatively correlated with that of IL-17A. miR-19a-5p could directly bind to the 3'UTR of IL-17A and regulate its expression. Both in vitro and in vivo studies demonstrated that miR-19a-5p mimics decreased the expression of IL-17A, RANK and Cathepsin K, while miR-19a-5p inhibitor significantly increased the expression of IL-17A, RANK, and Cathepsin K. Importantly, the Hyp could improve bone structure of OVX mice by enhancing miR-19a-5p-mediated IL-17A downregulation. Overall, these data demonstrated that miR-19a-5p/IL-17A axis might serve as novel therapeutic candidate for PMO. Hyp could relieve bone resorption by targeting the miR-19a-5p/IL-17A axis in OVX mice and exhibited prospective for the treatment of PMO.


Investigation on the ZBG-functionality of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase inhibitors.
A series of alternative Zn-binding groups were explored in the design of phenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors. Most of the synthesized compounds were less effective than the parent hydroxamic acid. However, the profile of activity shown by the analog bearing a hydroxyurea head group, makes this derivative promising for further investigation.


Necrotizing soft tissue infection of the chest wall.
Necrotizing soft tissue infection of the chest wall is a relatively rare but highly lethal surgical condition that has received little attention in the literature. The case of a 21-year-old female patient affected by this rare infection is reported. Our recent experience and literature data suggest that chest wall necrotizing soft tissue infection spreads rapidly and is highly lethal. High index of suspicion, early diagnosis, and aggressive approach are essential to its successful treatment.


Efficacy of an external urethral device in women with genuine stress urinary incontinence.
The efficacy of a new external anti-incontinence device in patients with a videourodynamic diagnosis of genuine stress incontinence (GSI) in an open longitudinal study is reported. Fourteen women with GSI underwent assessment before and after 3-4 weeks of device use. Assessment consisted of visual analog scores (VAS), quality of life (QOL) questionnaires, urine for culture and a 1 hour pad test. VAS scores showed a significant improvement for the symptom of stress incontinence (P<0.05). QOL scores improved significantly by 38% (P<0.05) and 29% (P<0.01) for the Incontinence Impact Questionnaire and Urogenital Distress Inventory, respectively. The mean pad weight decreased by 47% (P=0.056). Of the 9 women who had a positive pad test (>2 g) without the device, 5 were dry (<2 g) with the device (P<0.05). These preliminary data suggest that this device is effective in women with GSI.


Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms.
Constitutional aneuploidy occurs in at least 5% of recognised pregnancies, with apparent preferential involvement of the X chromosome and the smaller autosomes. Molecular cytogenetic investigations of cleavage-stage embryos have revealed anomalies affecting all sizes of chromosomes. The aim was to investigate the variety of anomalies arising during maternal meiosis I by analysis of unfertilised oocytes and polar bodies to gain insight into aneuploidy mechanisms. Sequential FISH analysis was carried out with specific probes derived from eight chromosomes, representing all sizes. Only imbalance due to a gain of a whole chromosome or chromatid, represented by extra signals, was counted to avoid artefact. Data were obtained on 236 eggs from 124 patients of average age 32.5 years (range 22-44). Ten patients (average 32.6 years) had abnormal eggs. The abnormality rate for oocytes and for polar bodies was close to 4% for each. Fourteen hyperploidies were found, seven involving additional single chromatids. The abnormalities affected chromosomes 13,16,18, 21 and X but not chromosomes 1, 9 or 12. The data provide evidence for several mechanisms leading to aneuploidy, including classical non-disjunction of whole univalents; pre-division of chromatids prior to anaphase I, leading to imbalance detected at metaphase II; gonadal mosaicism for a trisomic cell line and preferential involvement of the smaller chromosomes. Monosomy for the large autosomes is not uncommon in cleavage-stage embryos and may additionally arise from anaphase lag preferentially affecting such chromosomes.


Inhibition of nicotine-induced secretion from bovine chromaffin cells by the amidated C-terminal sequence of the opioid peptide amidorphin.
The nicotine-induced release of catecholamines and opioid peptides from bovine chromaffin cells is inhibited by the amidated opioid peptide amidorphin. The active site of this inhibitory activity is located at the peptide's C-Terminus, which is, in contrast to the N-terminal sequence TYR-GLY-GLY-PHE, not responsible for the opioidergic activity of opioid peptides. The noradrenaline-secretion induced by histamine, a non-cholinergic secretagogue, has not been inhibited by amidorphin.


Testing quality indicators and proposing benchmarks for physician-staffed emergency medical services: a prospective Nordic multicentre study.
A consensus study from 2017 developed 15 response-specific quality indicators (QIs) for physician-staffed emergency medical services (P-EMS). The aim of this study was to test these QIs for important characteristics in a real clinical setting. These characteristics were feasibility, rankability, variability, actionability and documentation. We further aimed to propose benchmarks for future quality measurements in P-EMS. In this prospective observational study, physician-staffed helicopter emergency services registered data for the 15 QIs. The feasibility of the QIs was assessed based on the comments of the recording physicians. The other four QI characteristics were assessed by the authors. Benchmarks were proposed based on the quartiles in the dataset. Nordic physician-staffed helicopter emergency medical services. 16 physician-staffed helicopter emergency services in Finland, Sweden, Denmark and Norway. The dataset consists of 5638 requests to the participating P-EMSs. There were 2814 requests resulting in completed responses with patient contact. All QIs were feasible to obtain. The variability of 14 out of 15 QIs was adequate. Rankability was adequate for all QIs. Actionability was assessed as being adequate for 10 QIs. Documentation was adequate for 14 QIs. Benchmarks for all QIs were proposed. All 15 QIs seem possible to use in everyday quality measurement and improvement. However, it seems reasonable to not analyse the QI 'Adverse Events' with a strictly quantitative approach because of a low rate of adverse events. Rather, this QI should be used to identify adverse events so that they can be analysed as sentinel events. The actionability of the QIs 'Able to respond immediately when alarmed', 'Time to arrival of P-EMS', 'Time to preferred destination', 'Provision of advanced treatment' and 'Significant logistical contribution' was assessed as being poor. Benchmarks for the QIs and a total quality score are proposed for future quality measurements.


Contralateral bone conducted sound wave propagation on the skull bones in fresh frozen cadaver.
The study aimed to investigate the efficient pathway for BC sound transmission by measuring vibrations on the opposite side of the skull bone, referred to as the mastoid position. The realistic contralateral transmission pathway of bone conduction (BC) vibrations is investigated through each osseous structure in the midlines of the fresh-frozen whole head. BC stimulation is applied to the mastoid using a bone vibrator, and acceleration responses are observed on the contralateral mastoid bone and seven midline points of skull bones using triaxial accelerometers. The study finds that the range showing the highest contralateral transmission efficiency of bone vibration is the intermediate frequency range with contralateral direction. Within this range, a significant amplitude of acceleration response is measured at the face-side points and the back and upper parts of the head. The thesis suggests that signal transmission from the specific midline to the mastoid can be more efficient than the conventional configuration of BC from the mastoid to the mastoid.


Robust cross-links in molluscan adhesive gels: testing for contributions from hydrophobic and electrostatic interactions.
The cross-linking interactions that provide cohesive strength to molluscan adhesive gels were investigated. Metal-based interactions have been shown to play an important role in the glue of the slug Arion subfuscus (Draparnaud), but other types of interactions may also contribute to the glue's strength and their role has not been investigated. This study shows that treatments that normally disrupt hydrophobic or electrostatic interactions have little to no effect on the slug glue. High salt concentrations and non-ionic detergent do not affect the solubility of the proteins in the glue or the ability of the glue proteins to stiffen gels. In contrast, metal chelation markedly disrupts the gel. Experiments with gel filtration chromatography identify a 40 kDa protein that is a central component of the cross-links in the glue. This 40 kDa protein forms robust macromolecular aggregations that are stable even in the presence of high concentrations of salt, non-ionic detergent, urea or metal chelators. Metal chelation during glue secretion, however, may block some of these cross-links. Such robust, non-specific interactions in an aqueous environment are highly unusual for hydrogels and reflect an intriguing cross-linking mechanism.


Histaminergic vasodilation of intracerebral arterioles in the rat.
Histamine from various sources is found in significant amounts around cerebral vessels and may play a significant role in controlling CBF. The effect of histamine on the intracerebral microcirculation has not been examined. We have used an in vitro technique for the isolation and cannulation of intracerebral arterioles from the rat to study the effect of histamine on the spontaneous tone developed by these vessels. Extraluminally administered histamine caused dose-dependent vasodilation of isolated intracerebral arterioles with a maximal dilation of 139 +/- 2.4% of control diameter. The dilation was blocked by the H2 receptor antagonist cimetidine, but was only incompletely attenuated by the H1 receptor blocker chlorpheniramine. Histamine effects a dilation of the spontaneous tone of intracerebral resistance vessels, which is mediated by H2 receptors.


Benign gastric ulcer as a cause of gastrocolic fistula. A report of 3 cases.
Three cases of gastrocolic fistula due to benign gastric ulcer seen during a 5-year period are presented. Although colonic or gastric malignancy is said to be the commonest cause of gastrocolic fistula, in the same period only 1 case due to colonic carcinoma was seen. The important role played by radiology in the diagnosis of gastrocolic fistula is emphasized and the clinical presentation is discussed, together with the possible role of analgesics in the aetiology.


Cutaneous complications associated with breast augmentation: A review.
Breast augmentation is one of the most popular and safe cosmetic procedures performed by plastic surgeons worldwide. Although breast implants are available in a number of different materials, silicone-filled implants remain the most common type. However, prior to the development of breast implants, various materials were injected into the soft tissues of the breasts to increase breast volume, which caused cutaneous complications and disfigurement. This review details the history of breast augmentation, the current methods used in augmentation surgery, and associated cutaneous complications.


How a B family DNA polymerase has been evolved to copy RNA.
We report here crystal structures of a reverse transcriptase RTX, which was evolved in vitro from the B family polymerase KOD, in complex with either a DNA duplex or an RNA-DNA hybrid. Compared with the apo, binary, and ternary complex structures of the original KOD polymerase, the 16 substitutions that result in the function of copying RNA to DNA do not change the overall protein structure. Only six substitutions occur at the substrate-binding surface, and the others change domain-domain interfaces in the polymerase to enable RNA-DNA hybrid binding and reverse transcription. Most notably, F587L at the Palm and Thumb interface stabilizes the open and apo conformation of the Thumb. The intrinsically flexible Thumb domain seems to play a major role in accommodating the RNA-DNA hybrid product distal to the active site. This is reminiscent of naturally occurring RNA-dependent DNA polymerases, including telomerase, which have a dramatically augmented Thumb domain, and of reverse transcriptase, which extends its Thumb with the RNase H domain.


Lung perfusion with protective solution relieves lung injury in corrections of Tetralogy of Fallot.
The aim of this study was to evaluate the protective effect of pulmonary perfusion with hypothermic protective solution on lung function after cardiopulmonary bypass in corrections of Tetralogy of Fallot. Sixty-four consecutive children with Tetralogy of Fallot were randomly divided into a control group (n = 30) and a protective group (n = 34). Hypothermic protective solution was infused to the main pulmonary artery in the protective group. Hemodynamics and lung functions were monitored. Concentrations of malondialdehyde, tumor necrosis factor-alpha, von Willebrand factor, and endothelin in plasma were measured. The interleukin-6 and interleukin-8 levels in bronchoalveolar lavage fluid were also determined. Lung biopsy specimens were obtained after weaning from cardiopulmonary bypass. Oxygenation values (oxygen index and alveolar-arterial O(2) gradient) were better preserved in the protective group than in the control group. The time of mechanical ventilation and length of intensive care unit stay were shorter in the protective group compared with the control group. The tumor necrosis factor-alpha and malondialdehyde levels in plasma increased in both groups after operations, and the rising extents were lower in the protective group than in the control group. The von Willebrand factor and endothelin levels in plasma increased more significantly in the control group than in the protective group. The concentrations of interleukin-6 and interleukin-8 in bronchoalveolar lavage fluid were lower in the protective group than in the control group. The examination of histopathology demonstrated capillary hyperemia and hemorrhage, intra-alveolar edema, leukocytes accumulation, mitochondria swelling and vacuolation, and gas-blood barrier broadening in the control group, whereas there were no significant changes in the protective group. The intercellular adhesion molecule-1 expression on lung vascular endothelial cells was stronger in the control group. Lung perfusion with hypothermic protective solution during cardiopulmonary bypass relieved lung injury in corrections of Tetralogy of Fallot. The inhibition of lung vascular endothelial cell injury may be the major mechanism of relieving cardiopulmonary bypass-induced lung injury.


Lymphokine-activated cell-associated antigen involved in broad-reactive killer cell-mediated cytotoxicity.
Spleen cells from rats which had been hyperimmunized with mouse lymphokine-activated killer (LAK) cells, were fused with the mouse myeloma cell line, P3 X 63 Ag8.653. Antibodies secreted by 1500 cultures were selected by their blocking effect on LAK cell-mediated cytotoxicity in the absence of complement. Two monoclonal antibodies (KBA4 and KBA6) greatly inhibited the cytotoxic activity of LAK cells, which were induced from mouse spleen cells by culture with recombinant human interleukin 2 (r-IL-2). These antibodies also blocked the cytotoxic activity of natural killer (NK) cells, but activated macrophages (A-M phi) were only slightly sensitive to them. However, no effect of the antibodies on the cytotoxic activity of cytotoxic T lymphocytes (CTL) was detected. These data suggest that the specific antigen, lymphokine-activated cell-associated (LAA) antigen, defined by these monoclonal antibodies may be associated with the recognition mechanisms of broad-reactive killer (BRK) cell-mediated cytotoxicity. The observation that low levels of LAA antigen are distributed in all lymphoid cells and that it was significantly enhanced by treatment of the cells with r-IL-2 suggests that the antigen may be involved in lymphocyte-activation mechanisms. We also found that the LAA antigen consists of two distinct polypeptides with Mr of 180,000 and 95,000 Da, which are similar to that of LFA 1 antigen. However, the biological characteristics of LAA antigen did not coincide with those of LFA 1. Therefore, KBA MAb may recognize a carbohydrate epitope distinct from that of LFA 1.


Family Members' Perspectives on Family and Social Support Available to Suicidal Patients, and Health Systems' Interactions and Responses to Suicide Cases in Alberta: Protocol for a Quantitative Research Study.
Suicide is a major cause of preventable death globally and a leading cause of death by injury in Canada. To support people who experience suicidal thoughts and behaviors and to ultimately prevent people from dying by suicide, it is important to understand individual and familial experiences with the health care system. We present the protocol for a study, the objective of which is to explore how people who died by suicide, and their family members, interacted with the health care system. This is a quantitative research study. Data will be collected through a self-administered paper-based or online survey of the family member of patients who died by suicide. The sample size was calculated to be 385 (margin of error ±3%). Data collection will start in October 2020 and results will be available by March 2021. We expect the results to shed light on the experiences of individuals who died by suicide and their family members with the health care system. The study has received ethical clearance from the Health Ethics Research Board of the University of Alberta (Pro00096342). Our study may inform practice, policy, and future research. The findings may shape how members of the health care system respond to people who are at risk of suicide and their families. PRR1-10.2196/19112.