Cerebrovascular disease in patients with pituitary tumors.
Several studies have shown that patients with acromegaly have increased mortality rates for cardiovascular disease and cerebrovascular disease (CVD). Similar associations have also been seen for patients with hypopituitarism or with non-functional pituitary adenomas. This review summarizes these data and discusses the relative importance of different risk factors for cardiovascular, especially CVD, mortality among patients with acromegaly or non-functional pituitary adenomas, and for those with hypopituitarism as a result of other causes.


Study of catalytic ozonation for tetracycline hydrochloride degradation in water by silicate ore supported Co3O4.
Tetracycline hydrochloride (TCH) degradation by cobalt modified silicate ore (CoSO) catalytic ozonation in aqueous solution was investigated. CoSO catalyst was synthesized by an impregnation method using Co(NO3)2 as the precursor and natural silicon ore (SO) as the support. The key catalyst preparation conditions (i.e., impregnation concentration, calcination temperature and time) were optimized. The activity and stability of CoSO catalyst and its catalytic ozonation mechanism for TCH degradation were studied. The results showed that Co3O4 was successfully coated on the silicon ore and the CoSO catalyst was highly efficient in catalytic ozonation for TCH degradation. The TCH removal by CoSO/O3 could reach 93.2%, while only 69.3% by SO/O3 and only 46.0% by O3 alone at 25 min. The reaction of TCH degradation followed pseudo-first order kinetics. TOC removal rate by CoSO/O3 was 2.0 times higher than that by SO/O3, and 3.5 times higher than that by O3 alone. The reaction conditions (TCH initial concentration, catalyst concentration, pH and temperature) for catalytic ozonation were systematically investigated. The possible mechanism for the CoSO catalytic ozonation process was proposed, where hydroxyl radical oxidation mainly accounted for the substantial TCH degradation. Furthermore, CoSO showed great durability and stability after seven reaction cycles.


[Soluble tumor necrosis factor related apoptosis inducing ligand (sTRAIL) and clinical outcome of HBV infection in human].
To explore the role of sTRAIL in the pathogenesis of HBV infection in human being. sTRAIL in 153 patients' sera was examined with ELISA. Correlations between sTRAIL and liver functional parameters were analysed. The levels of sTRAIL in patients with various clinical types of hepatitis B as well as primary hepatocellular carcinoma were all higher than that in normal persons and became almost normal in recovering stage cases. In acute and chronic HBV infection, sTRAIL level was negatively correlated with ALT, AST and total bilirubin levels, and positively correlated with serum albumin. The results indicated that higher level of sTRAIL expression is correlated with liver damage, and apoptosis induced by sTRAIL is one of the mechanisms of liver damage in HBV infection.


Association of increased lytic effector cell function with high estrogen receptor levels in tumor-bearing patients with breast cancer.
Tumor-bearing patients with breast cancer were assayed for their natural killer (NK) cell activity and for the function of activated cytotoxic T-cells, as assessed by lectin-dependent cellular cytotoxicity (LDCC). Tumor-bearing patients with breast cancer had a significant increase in NK activity and in LDCC, as compared with healthy control individuals. Although the enhanced NK cell activity and LDCC were closely associated with high levels (greater than 31 fmol/mg) of estrogen receptor (ER) content in the primary tumor, no other clinical or histologic correlation between the increase in either parameter of cytotoxic effector cell function could be found. Thus, ER levels greater than 31 fmol/mg might be associated with increased cytotoxic effector cell function in tumor-bearing patients with breast cancer.


The significance of HPA axis disturbance in panic disorder.
Agoraphobic and panic disorder patients underwent 1-mg Dexamethasone Suppression Tests (DST) before, during, and after an 8-week trial of diazepam, alprazolam, or placebo. Previously described, never-ill controls underwent similar testing. At baseline, 21 of 82 (25.6%) panic disorder and 5 of 38 (13.2%) controls were nonsuppressors. This difference grew more marked with multiple testing over a 2-month period; 18 of 44 (40.9%) panic disorder patients were nonsuppressors on at least 1 of 3 tests compared with only 5 of 35 (14.3%) controls (p = 0.006). DST results were related to severity, but not to the presence or absence, of depressive syndromes. Control for plasma dexamethasone levels left highly significant differences in postdexamethasone cortisol across diagnostic groups. Neither DST results nor plasma dexamethasone levels changed in concert with clinical change, and type of treatment had little differential effect on these measures. Nor did DST results predict subsequent course when active treatment was extended by 6 months. However, DST results during the initial 8 weeks of treatment were strongly related to relapse when medications were tapered, even though this occurred 6 months after the last DST.


Experimental bagassosis: role of infection.
The pathological lesions of bagassosis have been reproduced in guinea pigs given bagasse fibers along with low doses of actinomycete spores. In the early stages, interstitial infiltration with lymphocytes and macrophages as seen in humans was noted. Later, small interstitial bagasse granulomas composed of foreign body giant cells, fibroblasts, and lymphocytes developed, some of which had a laminated appearance. Lymph node changes consistent with an immunological reaction were observed. Actinomycetes alone showed occasional areas of pneumonitis and bagasse alone small granulomas consisting of foreign body giant cells and bagasse fibers. Finally, the combined effect of dust and actinomycetes produced interstitial fibrosis composed of thick reticulin fibers and occasional collagen fibers, which persisted to the end of the experiment. Bagasse alone and actinomycetes alone produced only thin reticulin fibers. It has been suggested that bagassosis is due to the synergistic action of bagasse fibers and Micropolyspora faeni and that in the pathogenesis of the syndrome an immunological component may be involved.


A rapid technique for alkaline phosphatase enzyme activity in tissues.
A rapid method is described for serial determination of alkaline phosphatase enzyme activity in the rat kidney and the developing avian vertebra by using an improved paraffin embedding process and a slide staining rack. Tissue samples fixed 12 to 24 h in 80% ethanol at 0 to 4 degrees C are dehydrated in absolute acetone at 0 to 4 degrees C, and then embedded in paraffin of 50 degrees C via benzene at room temperature. The alkaline phosphatase enzyme activity is essentially demonstrated with the method of GOMORI and TAKAMATSU but modified for the use of the slide staining rack. With the new technique, the enzyme activity is completely preserved and reproducible for years in the paraffin embedded tissues. The good quality of the sections enables quantitative evaluations by video scanning.


Preliminary analysis of hybrid laparoscopic procedure for resection of gastric submucosal tumors.
to evaluate the feasibility, safety and benefits of minimally invasive surgery for resection of gastric submucosal tumor (GSMT). we conducted a retrospective study of medical records of patients undergoing endoscopy-assisted laparoscopic resection of gastric submucosal tumors (prospectively collected) from 2011 to 2014. We evaluated clinical data, surgical approach, clinicopathological characteristics of the GSMT (size, location, histopathological and immunohistochemical exams), outcome and patients follow-up. we evaluated six patients, 50% male, mean age 52±18 years and common symptoms of heartburn and gastric fullness. All patients underwent hybrid procedure without anatomical impairment of the organ. The average length of stay was 3.5 days and the average size of the tumors was 2.0±0.8cm, five of them (83%) in the proximal third of the stomach. The surgical specimens pathological and immunohistochemistry examination revealed one case of ectopic pancreas (17%), one grade 2 neuroendocrine tumor (17%), one lipoma (17%), one GIST (17%) and two leiomyomas (32%). There were no episodes of tumor rupture or intraoperative complications and no conversion to open surgery. During the postoperative follow-up period, none of the patients had recurrence, metastasis, fistula or stenosis. the results showed that endoscopy-assisted laparoscopic resection is feasible and safe for patients with GSMT. Endoscopy proved to be essential in the location of lesions and as intraoperative support, especially when attempting to preserve the pylorus and cardia during surgery. avaliar a viabilidade, segurança e vantagens da cirurgia minimamente invasiva para ressecção de tumores submucosos gástricos (TUSG). estudo retrospectivo dos prontuários de pacientes submetidos à ressecção videolaparoscópica assistida por endoscopia digestiva alta para tumores submucosos gástricos (coletados prospectivamente) de 2011 a 2014. Os fatores avaliados foram dados clínicos, abordagem cirúrgica, características clinicopatológicas dos TUSG (tamanho, localização, exame anatomopatológico e imuno-histoquímico), resultados e acompanhamento dos pacientes. foram avaliados seis pacientes, 50% do sexo masculino, com média de idade 52±18 anos e sintomas comuns de pirose e plenitude gástrica. Todos os pacientes foram submetidos ao procedimento híbrido e sem comprometimento anatômico do órgão. O tempo médio de internação foi 3,5 dias e o tamanho médio dos tumores foi 2,0±0,8cm, cinco deles (83%) no terço proximal do estômago. Os exames anatomopatológicos e imuno-histoquímicos das peças cirúrgicas demonstraram um caso de pâncreas ectópico (17%), um tumor neuroendócrino grau 2 (17%), um lipoma (17%), um GIST (17%) e dois leiomiomas (32%). Não houve episódios de ruptura do tumor nem complicações intraoperatórias e nenhuma conversão para cirurgia aberta. Durante o período de acompanhamento pós-operatório nenhum dos pacientes apresentou recidiva, metástase, fístula ou estenose. os resultados obtidos mostraram que a ressecção laparoscópica assistida por endoscopia é viável e segura para pacientes com TUSG. A endoscopia mostrou-se fundamental na localização das lesões e suporte intraoperatório, principalmente na tentativa de preservar a cárdia e o piloro durante a cirurgia.


Differential synthesis of lens proteins in the presence of m7G(5')pppG and cleavage product m7GMP in an embryonic chick lens cell lysate.
The effect of m7GMP release from m7GMP-containing mRNA cap sequence m7GpppG by the embryonic chick lens m7GpppN-pyrophosphatase activity on the synthesis of lens proteins was examined in a newly developed homologous translation system derived from 15-day embryonic chick lenses. The synthesis of total lens polypeptides and delta-crystallin polypeptides, the major translation product, was inhibited 84% and 88%, respectively, by 0.5 mM m7GpppG; m7GMP (0.5 mM) inhibited total synthesis by 63% but was 33% less inhibitory toward delta-crystallin synthesis; GpppG and GMP were not inhibitors, m7GpppG inhibited met-tRNAfmet incorporation into 80S initiation complexes.


Endometrial Adenocarcinoma in SurePath™ Cervical Samples: Cytological Features Revisited.
The cytomorphological criteria of malignant endometrial lesions in cervical samples are less well described than those of cervical lesions. We wished to investigate if there were features in SurePath™ liquid-based cytology samples that would facilitate more accurate differentiation between benign and malignant endometrial cells. This was a two-phase study, with a review of all SurePath™ samples reported as endometrial adenocarcinoma (n = 42) evaluating 12 cytological features in the first phase. In phase 2 (test set), all initial cases plus an additional 83 cases were reviewed using these 12 cytological features to predict the outcome. Out of 12 cytological features evaluated in phase 1 (training set), nuclear chromatin pattern, apoptotic bodies and tingible body macrophages were found to be the most significant features determining malignant histological outcome. These 12 cytological features were re-evaluated in phase 2 (n = 125). Of 125 cases, 54 had a benign and 71 had a malignant or premalignant histological outcome, with a positive predictive value of 56.8%. Granular nuclear chromatin, tingible body macrophages and apoptosis in the background are the most significant factors in determining whether endometrial cells present in cervical samples represent malignancy or are benign. Using these features, relatively accurate predictions of endometrial pathology can be made.


Endometriosis-associated infertility treated by long-term gonadotropin-releasing hormone agonist administration and assisted fertilization.
Two patients with long-lasting infertility associated with moderate and severe symptomatic endometriosis were treated with long-term GnRH-agonist suppression of ovarian function. Both patients were relieved of their endometriosis-related abdominal pains during the first treatment month. After an additional treatment period of 3 to 5 months, assisted fertilization was performed, resulting in an ongoing pregnancy for both patients.


Gender and geographic differences in the prevalence of autism spectrum disorders in children: analysis of data from the national disability registry of Taiwan.
The prevalence of autism spectrum disorders (ASD) in the world has increased dramatically in the recent decades. However, data at the national level are limited, and geographic differences are seldom evaluated. According to the law, the local governments in Taiwan began to certify disabled residents and provide various services in 1980, and the central government maintains a registry of certified cases. The registry started to enroll cases of ASD in 1990, providing a unique opportunity for studying ASD at the national level. Because the government discourages the certification under 3 years of age, we limited our analyses to those who were at least 3 years old. Using the registry data from 2004 to 2010, we calculated the prevalence of ASD by age, gender, and geographic area and assessed the changes over time. From 2004 to 2010, the registered cases between 3 and 17 years old increased from 3995 to 8072 annually, and the prevalence generally increased every year in all age groups (p<0.01). In each year there were more boy cases than girl cases, and the prevalence rate ratio ranged from 5.64:1 to 6.06:1 (p<0.01 in all years), with an increasing trend over time (p<0.01). A higher prevalence was observed in the urban areas over the years, and the prevalence rate ratio ranged from 2.24:1 to 2.72:1 (p<0.01 in all years), with a decreasing trend over time (p<0.01).


Impact of connecting tuberculosis directly observed therapy short-course with smoking cessation on health-related quality of life.
With evolving evidence of association between tuberculosis (TB) and tobacco smoking, recommendations for the inclusion of tobacco cessation interventions in TB care are becoming increasingly important and more widely disseminated. Connecting TB and tobacco cessation interventions has been strongly advocated as this may yield better outcomes. However, no study has documented the impact of such connection on health-related quality of life (HRQoL). The objective of this study was to document the impact of an integrated TB directly observed therapy short-course (DOTS) plus smoking cessation intervention (SCI) on HRQoL. This was a multi-centered non-randomized controlled study involving 120 TB patients who were current smokers at the time of TB diagnosis in Malaysia. Patients were assigned to either of two groups: the usual TB-DOTS plus SCI (SCIDOTS group) or the usual TB-DOTS only (DOTS group). The effect of the novel strategy on HRQoL was measured using EQ-5D questionnaire. Two-way repeated measure ANOVA was used to examine the effects. When compared, participants who received the integrated intervention had a better HRQoL than those who received the usual TB care. The SCIDOTS group had a significantly greater increase in EQ-5D utility score than the DOTS group during 6 months follow-up (mean ± SD = 0.98 ± 0.08 vs. 0.91 ± 0.14, p = 0.006). Similarly, the mean scores for EQ-VAS showed a consistently similar trend as the EQ-5D indices, with the scores increasing over the course of TB treatment. Furthermore, for the EQ-VAS, there were significant main effects for group [F (1, 84) = 4.91, p = 0.029, η2 = 0.06], time [F (2, 168) = 139.50, p = < 0.001, η2 = 0.62] and group x time interaction [F (2, 168) = 13.89, p = < 0.001, η2 = 0.14]. This study supports the evidence that an integrated TB-tobacco treatment strategy could potentially improve overall quality of life outcomes among TB patients who are smokers.


Attosecond coherent manipulation of electrons in tunneling microscopy.
Nanoelectronic devices operating in the quantum regime require coherent manipulation and control over electrons at atomic length and time scales. We demonstrate coherent control over electrons in a tunnel junction of a scanning tunneling microscope by means of precise tuning of the carrier-envelope phase of two-cycle long (<6-femtosecond) optical pulses. We explore photon and field-driven tunneling, two different regimes of interaction of optical pulses with the tunnel junction, and demonstrate a transition from one regime to the other. Our results show that it is possible to induce, track, and control electronic current at atomic scales with subfemtosecond resolution, providing a route to develop petahertz coherent nanoelectronics and microscopy.


Root canal systems in mandibular first premolars with C-shaped root configurations. Part I: Microcomputed tomography mapping of the radicular groove and associated root canal cross-sections.
The purpose of this study was to investigate the morphology of the radicular grooves and root canal cross-sections in mandibular first premolars that exhibit a C-shaped root. Eighty-six mandibular first premolars with C-shaped roots were scanned from the coronal to anatomical apex using microCT80. The location, length, and depth of the radicular grooves were measured. The cross-sectional morphology of root canal systems was evaluated at 11 levels. Results were subject to the Kruskal-Wallis test. Of the 86 C-shaped roots, a total of 93 radicular grooves were noted. Most of the grooves (78.5%) were located on the mesiolingual surface of the root. The C-shaped canal could vary considerably in shape at different levels, and the incidence of two canals at the middle and apical was 21% and 80%, respectively. This study shows that radicular grooves may present relevant morphologic variations in the root canal system when the C-shaped root is present.


Palladium-catalyzed allylic C-H amination of alkenes with N-fluorodibenzenesulfonimide: water plays an important role.
A new palladium-catalyzed highly regioselective allylic C-H amination of alkenes with NFSI in the presence of a catalytic amount of water was developed and successfully expanded to Selectfluor-mediated palladium-catalyzed aminations of alkenes with N-tosylcarbamates in water at room temperature.


Co-Expression of Coxsackievirus/Adenovirus Receptors and Desmoglein 2 in Lung Adenocarcinoma: A Comprehensive Analysis of Bioinformatics and Tissue Microarrays.
Coxsackievirus/adenovirus receptors (CARs) and desmoglein-2 (DSG2) are similar molecules to adenovirus-based vectors in the cell membrane. They have been found to be associated with lung epithelial cell tumorigenesis and can be useful markers in predicting survival outcome in lung adenocarcinoma (LUAD). A gene ontology enrichment analysis disclosed that DSG2 was highly correlated with CAR. Survival analysis was then performed on 262 samples from the Cancer Genome Atlas, forming "Stage 1A" or "Stage 1B". We therefore analyzed a tissue microarray (TMA) comprised of 108 lung samples and an immunohistochemical assay. Computer counting software was used to calculate the H-score of the immune intensity. Cox regression and Kaplan-Meier analyses were used to determine the prognostic value. CAR and DSG2 genes are highly co-expressed in early stage LUAD and associated with significantly poorer survival (p = 0.0046). TMA also showed that CAR/DSG2 expressions were altered in lung cancer tissue. CAR in the TMA was correlated with proliferation, apoptosis, and epithelial-mesenchymal transition (EMT), while DSG2 was associated with proliferation only. The Kaplan-Meier survival analysis revealed that CAR, DSG2, or a co-expression of CAR/DSG2 was associated with poorer overall survival. The co-expression of CAR/DSG2 predicted a worse overall survival in LUAD. CAR combined with DSG2 expression can predict prognosis.


[The effect of Clostridium difficile infection on length of hospital stay. A cohort study].
Clostridium difficile is responsible for a spectrum of diseases known as "Clostridium difficile infection" (CDI). It is currently the leading cause of nosocomial diarrhea in developed countries. This infection has been associated with both increased hospital stay and mortality, and to a greater likelihood of readmission. In our country these undesirable effects have not yet been characterized. Our objective was to quantify the increase in hospital stay attributable to infection by C.difficile. A retrospective cohort study matched by age, sex and admission date, was conducted in a tertiary care university hospital during an outbreak of nosocomial transmission of CDI. The cohort study included 38 infected, and 76 non-infected patients. Patients who developed CDI showed a higher proportion of malnutrition at admission (OR=10.3; 3.6 to 29.6), were exposed to a wider range of antibiotics (mean difference=1.5; 0.7-2.2), had a higher mortality (31.6% vs. 6.6% of controls, P<.001), and a longer hospital stay (median 31.5 days versus 5.5 days for controls, P<.001). After adjustment, infection by C.difficile was associated with an increase in hospital stay of 4 days (P<.001). C.difficile infection has important consequences on the length of hospital stay, and therefore on health costs.


Orocutaneous Fistula Formation in Free Flap Reconstruction for Oral Squamous Cell Carcinoma.
The aim of this study is to identify the risk factors associated with orocutaneous fistula (OCF) formation after free flap reconstruction for oral squamous cell carcinoma (SCC). Patients undergoing free flap reconstruction for oral SCC were retrospectively enrolled. The relationship between clinicopathologic variables and OCF formation was analyzed by univariate and multivariate analyses. A total of 87 OCFs occurred in 856 patients. Univariate analysis revealed cachexia, tumor at the tongue/floor of the mouth (TFOM), T4 stage, preoperative hemoglobin level, pull-through procedure, preoperative albumin level, and surgical site infection were associated with the formation of OCF. Multivariate analysis confirmed the independence of cachexia, TFOM, T4 stage, and surgical site infection in predicting OCF development. Conventional wound care could achieve successful fistula closure in 82.4% of the patients with a median time of 28 days. OCF formation was common after free flap reconstruction. The presence of cachexia, TFOM tumor site, T4 stage, and surgical site infection significantly increased the risk of OCF formation. Although it required a long period, conventional wound care can obtain satisfactory outcomes in OCF management.


Sequence analysis of a proteolyzed site in Drosophila choline acetyltransferase.
The amino terminal sequence of the 13-kilodalton (kD) polypeptide present in purified Drosophila acetyl-CoA: choline-O-acetyltransferase (EC 22.214.171.124) was determined, and its position in the sequence of the intact enzyme was located. Enzyme polypeptides for sequencing were obtained from native enzyme protein by denaturation, followed by fractionation on reverse-phase HPLC. The 13-, 54-, and 67-kD polypeptides recovered from the separation were subjected to amino terminal sequencing. Only the 13-kD fragment yielded a sequence. The 67- and 54-kD polypeptides appeared completely blocked to gas-phase Edman sequencing. The location of the amino terminal sequence from the 13-kD polypeptide in the cDNA-deduced enzyme sequence indicated that this fragment represents the carboxyl portion of the 67-kD enzyme, with the 54-kD polypeptide providing the amino terminal portion. The proteolysis that gave rise to the 13-kD polypeptide occurred at the carboxyl side of a monobasic lysine residue. An earlier comparison of the enzyme from Drosophila and pigs indicated that the cleaved lysine may be a conserved residue in the porcine enzyme. The cleaved enzyme region characterized in this study does not coincide with the regions of high homology found in the two enzymes, but hydrophilicity profiles generated for this area showed similarities.


Relationship between internal derangement of the temporomandibular joint and dentofacial morphology in women with anterior open bite.
Anterior open bite is known to be associated with internal derangement of the temporomandibular joint (TMJ). This study examined the relationships between internal derangement and dentofacial morphology in women with anterior open bite. Fifty-one women with anterior open bite were enrolled in this study. The sample was divided into 3 groups based on magnetic resonance imaging of bilateral TMJs: normal disk position, disk displacement with reduction, and disk displacement without reduction. One-way analysis of variance was used to compare the 3 groups with respect to the cephalometric variables, and Duncan's multiple comparisons were performed at the 95% confidence level to identify the differences among the 3 groups. Internal derangement of the TMJ was much more prevalent in subjects with a more posteriorly rotated mandibular ramus, a smaller mandible, and a greater tendency for a skeletal Class II pattern, although all subjects had an anterior open bite. These patterns were more severe as the internal derangement progressed to disk displacement without reduction. Some cephalometric characteristics, such as a decrease in posterior facial height, decrease in ramus height, and backward rotation and retruded position of the mandible, are associated with TMJ internal derangement in women with anterior open bite.


Whole blood optical biosensor.
The future of rapid point-of-care diagnostics depends on the development of cheap, noncomplex, and easily integrated systems to analyze biological samples directly from the patient (e.g. blood, urine, and saliva). A key concern in diagnostic biosensing is signal differentiation between non-specifically bound material and the specific capture of target molecules. This is a particular challenge for optical detection devices in analyzing complex biological samples. Here we demonstrate a porous silicon (PSi) label-free optical biosensor that has intrinsic size-exclusion filtering capabilities which enhances signal differentiation. We present the first demonstration of highly repeatable, specific detection of immunoglobulin G (IgG) in serum and whole blood samples over a typical physiological range using the PSi material as both a biosensor substrate and filter.


Hyaluronidase isoforms from developing embryos of the camel tick Hyalomma dromedarii.
Changes in hyaluronidase activity in the camel tick Hyalomma dromedarii were followed throughout embryogenesis. Peak activity of the enzyme on days 21 and 24 during development was accompanied with a complete organization of larvae before hatching on day 27. During purification of hyaluronidase to homogeneity, ion exchange chromatography lead to four forms (HAase1, 2, 3 and 4). HAase2 and HAase4 with highest purity and specific activities after chromatography on Sephacryl S-200. The apparent molecular masses of HAase2 and HAase4 were 25 and 40 kDa, respectively. HAase2 and HAase4 had the same pH optimum of 3.6 and Km values of 0.3 and 0.34 mg/mL hyaluronic acid, respectively. Cleaving activities of HAase2 and HAase4 were demonstrated in the order: hyaluronic acid>chondroitin sulphate A>chondroitin sulphate C>chondroitin sulphate mixed>chondroitin sulphate B>heparin, low M.Wt>heparin. HAase2 and HAase4 had the same temperature optimum (40 degrees C) with heat stability up to 40 degrees C. H. dromedarii HAase2 and HAase4 had broad plateau of NaCl requirement with optimum activity recorded at 0.15 and 0.3 M NaCl, respectively. HAase2 and HAase4 were inhibited by Ca2+, Fe3+, Co2+ and Hg2+ and enhanced by Mg2+ and Mn2+.


Establishing proof of concept for sonolucent cranioplasty and point of care ultrasound imaging after posterior fossa decompression for Chiari malformation.
Evaluation after posterior fossa decompression for Chiari malformation can require repeated imaging, particularly with persistent symptoms. Typically, CT or MRI is used. However, CT carries radiation risk and MRI is costly. Ultrasound is an inexpensive, radiation-free, point-of-care modality that has, thus far, been limited by intact skull and traditional cranioplasty materials. Ultrasound also allows for imaging in different head positions and body postures, which may lend insight into cause for persistent symptoms despite adequate decompression on traditional neutral static CT or MRI. We evaluate safety and feasibility of ultrasound as a post-operative imaging modality in patients reconstructed with sonolucent cranioplasty during posterior fossa decompression for Chiari malformation. Outcomes were analyzed for 26 consecutive patients treated with a Chiari-specific sonolucent cranioplasty. This included infection, need for revision, CSF leak, and pseudomeningocele. Ultrasound was performed point-of-care in the outpatient clinic by the neurosurgery team to assess feasibility. In eight months mean follow up, there were no surgical site infections or revisions with this novel sonolucent cranioplasty. Posterior fossa anatomy was discernable via transcutaneous ultrasound obtained point-of-care in the clinic setting at follow up visits. We demonstrate proof of concept for ultrasound as a post-operative imaging modality after posterior fossa decompression for Chiari malformation. With further investigation, ultrasound may prove to serve as an alternative to CT and MRI in this patient population, or as an adjunct to provide positional and dynamic information. Use of sonolucent cranioplasty is safe. This technique deserves further study.


Merremia tridentata as a supplementary feed to the grass Panicum maximum for young West African Dwarf sheep.
The provision ad libitum of the browse plant Merremia tridentata as a free-choice supplement to the grass Panicum maximum led to a significant increase in the total food intake of groups of five West African Dwarf sheep, although the increase in weight gain was not significant. The protein content of M. tridentata was higher than that of the grass and its tannin content was not sufficient to render it unpalatable.


Global trends in research of glutamate in epilepsy during past two decades: A bibliometric analysis.
Epilepsy affects more than 70 million people in the world. It is characterized by recurrent spontaneous seizures, and it is related to many neurological, cognitive, and psychosocial consequences. Glutamate neurotransmitter dysfunction has essential functions in the pathophysiology of epilepsy. In this work, bibliometric analysis was conducted to explore the trends, frontiers, and hotspots of the global scientific output of glutamate in epilepsy research in the past 20 years. The Science Citation Index Expanded of the Web of Science Core Collection (WoSCC) was searched to obtain information on publications and records published between 2002 and 2021. VOSviewer and CiteSpace were used to conduct bibliometric and visual analyses on the overall distribution of annual output, major countries, active institutions, journals, authors, commonly cited literature, and keywords. The impact and quality of the papers were assessed using the global citation score (GCS). Four thousand eight hundred ninety-one publications were retrieved in total. During the past two decades, the number of publications (Np) associated with glutamate in epilepsy has risen yearly. The United States has published the most papers; its H-index and number of citations are also the highest. The League of European Research Universities (LERU) was the most productive institution. In 2016, the total score of the paper written by Zhang Y was 854, ranking first. The keywords that appear most frequently are "epilepsy," "glutamate," "temporal lobe epilepsy (TLE)," "hippocampus," and "seizures." This study showed that although the publications related to epileptic glutamate fluctuated slightly, the Np increased overall. The United States is a great creator and influential country in this field. The first three authors are Eid, T., Aronica, E., and Smolders, I. "spectrum," "animal model," "inflammation," "mutation," "dysfunction," and "prefrontal cortex" are increasing research hotspots. By recognizing the most critical indicators (researchers, countries, research institutes, and journals of glutamate release in epilepsy research), the research hotspot of glutamate in epilepsy could help countries, scholars, and policymakers in this field enhance their understanding of the role of glutamate in epilepsy and make decisions.


Bis-exo-2-norbornylboron triflate for stereospecific enolization of 3,3,3-trifluoropropionates.
The first boron-mediated enolization-aldolization of 3,3,3-trifluoropropionates has been reported. The preparation and application of bis-exo-bicyclo[2.2.1]heptan-2-ylboron triflate as a superior reagent for diastereospecific enolization has also been described.


Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with multiple synchronous carcinoid tumors.
The spectrum of pulmonary neuroendocrine cell proliferation ranges from reactive hyperplasia to small cell carcinoma and includes diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. A case is reported and features of this disease are described according to the published evidence. The entity was first included in the WHO classification of tumors in 1999 and is considered a preneoplastic condition for carcinoid tumors. Patients generally report slowly progressive dyspnea and cough, and have airflow obstruction, multiple pulmonary nodules and/or radiological signs of air trapping, although asymptomatic cases with normal pulmonary function have been described. Histologically, it is characterized by neuroendocrine cell proliferation in the airway epithelium, in most cases beyond the basal membrane forming tumorlets and carcinoid tumors that are frequently multiple. The prognosis is favorable in most cases.


A mesoscale model of G1/S phase transition in liver regeneration.
The liver regenerates and maintains its function and size after injury by counterbalancing cell death with compensatory cell division. During liver regeneration, injured sites release cytokines, which stimulate normally quiescent hepatocytes to re-enter cell division cycle. Using a mesoscale approach, we have implemented the first mathematical model that describes cytokine-induced dedifferentiation of hepatocytes and the subsequent initiation of DNA synthesis (G0/G1 and G1/S phase transitions of the cell cycle). The model accurately reproduces experimentally measured kinetics of various signaling intermediates and DNA synthesis in hepatocytes for varying degrees of liver damage, in both wild type and knockout backgrounds. Liver regeneration is known to be a robust process, as liver mass reconstitution still occurs in various knockout mice (albeit with different kinetics). We analyze the robustness of the model using methods of control analysis. Moreover, we discuss the system's bandpass filtering properties and delays, which arise from feedbacks and nested feed-forward loops.


Clinical study on the treatment of primary trigeminal neuralgia by robot-assisted percutaneous balloon compression.
C-arm-guided percutaneous puncture balloon compression alone has risk factors of puncture failure, complications, and poor prognosis. Robot-assisted PBC can effectively increase the one-time puncture success rate and improve the safety of the procedure. However, evidence on the superiority of robot-assisted PBC over C-arm-guided PBC alone remains relatively limited. Retrospective analysis The clinical data of 60 patients with trigeminal neuralgia aged 60 years or older in the Department of Neurosurgery of the Fourth Hospital of Harbin Medical University from January 2021 to October 2021. There were 29 males and 31 females, and the patients' ages ranged from 60 to 79 years, with an average of 71.63 ± 5.12 years. Two groups were divided according to the surgical method, the C-arm guidance-only group (30 cases, n = 30) and the robot-assisted group (30 cases, n = 30). The success rate of first puncture, total operation time, number of "pear-shaped" balloons, number of C-arm x-ray scans, and immediate postoperative relief rate were recorded in both groups, and follow-up was performed to evaluate the postoperative results and complications. The overall evaluation of postoperative results and complications was performed. Intraoperative balloon compression was successfully completed in all 60 patients, and the first puncture success rate was higher in the robot-assisted group than in the simple C-arm group, with a significant difference between the two groups (P < 0.001). In terms of intraoperative balloon morphology, the number of "pear-shaped" balloons was higher in the PBC than in the C-arm-only PBC group, with a significant difference between the two groups (P < 0.005). The degree of immediate postoperative remission in the robotic group was 0 VAS score, which was not statistically significant in both groups (P > 0.05). By the final follow-up, the mean VAS score of the robot-assisted group was lower than that of the simple C-arm group, and both were statistically significant (P < 0.05); complications of masticatory muscle weakness or abnormal facial sensation occurred in both groups after surgery, but the number of cases in the robot-assisted group was less than that of the simple C-arm group. Robot-assisted PBC is better than PBC with a C-arm x-ray machine in terms of first puncture success rate, number of intraoperative balloon "pear-shaped" cases, number of C-arm x-ray scans and short-term efficacy.


A multivariate blood metabolite algorithm stably predicts risk and resilience to major depressive disorder in the general population.
Socioeconomic pressures, sex, and physical health status strongly influence the development of major depressive disorder (MDD) and mask other contributing factors in small cohorts. Resilient individuals overcome adversity without the onset of psychological symptoms, but resilience, as for susceptibility, has a complex and multifaceted molecular basis. The scale and depth of the UK Biobank affords an opportunity to identify resilience biomarkers in rigorously matched, at-risk individuals. Here, we evaluated whether blood metabolites could prospectively classify and indicate a biological basis for susceptibility or resilience to MDD. Using the UK Biobank, we employed random forests, a supervised, interpretable machine learning statistical method to determine the relative importance of sociodemographic, psychosocial, anthropometric, and physiological factors that govern the risk of prospective MDD onset (total n = 15,710). We then used propensity scores to rigorously match individuals with a history of MDD (n = 491) against a resilient subset of individuals without an MDD diagnosis (retrospectively or during follow-up; n = 491) using an array of key social, demographic, and disease-associated drivers of depression risk. 381 blood metabolites and clinical chemistry variables and 4 urine metabolites were integrated to generate a multivariate random forest-based algorithm using 10-fold cross-validation to predict prospective MDD risk and resilience. In unmatched individuals, a first case of MDD, with a median time-to-diagnosis of 72 years, can be predicted using random forest classification probabilities with an area under the receiver operator characteristic curve (ROC AUC) of 0.89. Prospective resilience/susceptibility to MDD was then predicted with a ROC AUC of 0.72 (x˜ = 3.2 years follow-up) and 0.68 (x˜ = 7.2 years follow-up). Increased pyruvate was identified as a key biomarker of resilience to MDD and was validated retrospectively in the TwinsUK cohort. Blood metabolites prospectively associate with substantially reduced MDD risk. Therapeutic targeting of these metabolites may provide a framework for MDD risk stratification and reduction. New York Academy of Sciences' Interstellar Programme Award; Novo Fonden; Lincoln Kingsgate award; Clarendon Fund; Newton-Abraham studentship (University of Oxford). The funders had no role in the development of the present study.


Levonorgestrel-releasing intrauterine system vs. systemic medication or blank control for women with dysmenorrhea: Systematic review and meta-analysis of randomized controlled trials.
To compare efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) with systemic medication or blank control in the treatment of dysmenorrhea. PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI) and Wanfang Data were searched to collect randomized controlled trials (RCTs) comparing LNG-IUS with systemic medication or blank control among women diagnosed with primary dysmenorrhea or secondary dysmenorrhea (adenomyosis or endometriosis) from inception to 2020.04. Der Simonian-Laird random-effect model was used to pool data. Seventy-one RCTs (6551 patients) were included. Overall bias risk was medium. Sixty-two articles enrolled patients with adenomyosis; LNG-IUS significantly reduced the visual analogue scale (VAS) score compared with the systemic medication group among adenomyosis women at 3 months (standardized mean difference (SMD) = -0.81, 95% confidence interval (CI) -1.22 to -0.40); 6 months (SMD = -1.25, 95%CI: -1.58 to -0.92); 9 months (SMD = -1.23, 95%CI: -1.63 to -0.83); 12 months (SMD = -1.66, 95%CI: -2.14 to -1.18). No difference was found in the incidence of irregular vaginal bleeding (16 RCTs; RR = 0.91, 95%CI: 0.62-1.33, P = 0.63, I 2 = 4%) and other adverse outcomes. Sensitivity analysis regarding randomization methods was robust. Nine RCTs enrolled endometriosis women. Pooling results showed no significant difference between LNG-IUS and systemic medication treatment in terms of VAS at 6 months (SMD = -0.27, 95% CI: -0.97-0.43). Moreover, LNG-IUS was associated with higher risk of irregular vaginal bleeding (26.8% vs. 0). LNG-IUS was associated with a reduced severity of dysmenorrhea compared with systemic medication; it was also beneficial for better control of menstrual blood loss and fewer adverse outcomes. Owing to small sample sizes, further well-designed RCTs are warranted to confirm these findings and long-term effects of LNG-IUS in the treatment of dysmenorrhea. https://www.crd.york.ac.uk/prospero/, identifier: CRD42021228343.


Convergence insufficiency in Chinese high school students.
The frequency of convergence insufficiency was determined in a sample of Chinese high school students. The associations between the frequency of convergence insufficiency, gender, refractive error and accommodative insufficiency were investigated. This was a single-site, prospective cross-sectional study. In total, 928 eligible teenagers (mean age 15.9 ± 0.8) from a local high school in Guangzhou, Guangdong Province, China participated in this study. Refraction and binocular vision tests were performed on all eligible participants. The following three signs were used to classify participants: sign 1, exophoria at near at least 4▵ greater than at far; sign 2, receded near point of convergence (≥ 6 cm break point); and sign 3, insufficient near positive fusional vergence (that is, failing Sheard's criterion or ≤ 15▵ break point). Diagnostic groups of convergence insufficiency classification were defined as follows: (1) 3-Sign convergence insufficiency (all three signs present); (2) 2-Sign convergence insufficiency (sign 1 plus sign 2 or 3); (3) 1-Sign convergence insufficiency (sign 1 only); and (4) no convergence insufficiency (that is, participants not classified into one of the above groups). The number and frequency of individuals with 3-Sign, 2-Sign, and 1-Sign convergence insufficiency as well as no convergence insufficiency group were 25 (2.7 per cent), 119 (12.8 per cent), 303 (32.6 per cent) and 481 (51.8 per cent), respectively. Gender (χ2 = 36.6, df = 3, p < 0.001), refractive error grouping (χ2 = 37.7, df = 9, p < 0.001) and accommodative insufficiency (χ2 = 15.4, df = 3, p = 0.002) were all significantly associated with convergence insufficiency. Male gender, hyperopia, or accommodative insufficiency were more likely to be classified with 3-Sign convergence insufficiency. The frequency of accommodative insufficiency was 9.5 per cent (88 of 928 participants). Compared to the data from school- and clinic-based populations in the USA and South Africa, the data from this sample of Chinese high school students showed a lower frequency of 3-Sign convergence insufficiency (2.7 per cent). Convergence insufficiency was associated with refractive error, gender and accommodative insufficiency.


Gastroenteritis outbreak associated with unpasteurized tempeh, North Carolina, USA.
During an investigation of an outbreak of gastroenteritis caused by Salmonella enterica serovar Paratyphi B variant L(+) tartrate(+), we identified unpasteurized tempeh as a novel food vehicle and Rhizopus spp. starter culture as the source of the contamination. Safe handling of uncooked, unpasteurized tempeh should be emphasized for prevention of foodborne illnesses.


Hypertension care cascade in Chile: a serial cross-sectional study of national health surveys 2003-2010-2017.
Trend data on hypertension prevalence and attainment indicators at each step of the care cascade (awareness, treatment, control) are required in Chile. This study aims to quantify trends (2003-2017) in prevalence and in the proportion of individuals with hypertension attaining each step of the care cascade among adults aged 17 years or older, and to assess the impact of lowering the blood pressure (BP) thresholds used to define elevated BP on these indicators. We used data from 2003, 2010, and 2017 Chilean national health surveys. Each year we assessed levels of (1) mean systolic (SBP) and diastolic (DBP) blood pressure, (2) hypertension prevalence (BP ≥ 140/90 mmHg or use of antihypertensive treatment), and (3) awareness, treatment, and control. Logistic regression on pooled data was used to assess trends in binary outcomes; linear regression was used to assess trends in continuous SBP and DBP. We compared levels of hypertension prevalence using two sources to ascertain antihypertensive treatment (self-reported versus medicine inventory). The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines were used to re-define hypertension using lower thresholds (BP ≥ 130/80 mmHg). Hypertension prevalence was 34.0, 32.0 and 30.8% in 2003, 2010 and 2017, respectively. Levels of treated- and controlled-hypertension were significantly higher in 2017 than in 2003 (65% versus 41% for treatment, P < 0.001; 34% versus 14% for control, P < 0.001), while levels of awareness were stable (66% versus 59%, P = 0.130). Awareness, treatment, and control levels were higher among females in 2003, 2010, and 2017 (P < 0.001). Mean SBP and DBP decreased over the 15-year period, except for SBP among females on treatment. Adopting the 2017 ACC/AHA guidelines would increase hypertension prevalence by 17 and 55% in absolute and relative terms, respectively. Chile has experienced a positive population-wide lowering in blood pressure distribution which may be explained partly by a significant rise in levels of treated- and controlled-hypertension since 2003. Lowering the thresholds used to define elevated BP would substantially increase the financial public health challenge of further improving attainment levels at each step of the care cascade. Innovative and collaborative strategies are needed to improve hypertension management, especially among males.


Six month postoperative hemodynamics of the Hancock heterograft and the Björk-Shiley prosthesis: results of a Veterans Administration cooperative prospective randomized trial.
In a Veterans Administration Cooperative Study involving 13 medical centers, 575 patients undergoing single valve replacement were prospectively randomized to receive either the standard Björk-Shiley prosthesis or the Hancock porcine heterograft (with a modified orifice for sizes 23 and smaller). The hemodynamic data in the 268 patients who underwent cardiac catheterization an average of 6 months (range 3 to 12) postoperatively are reported. Statistical analyses were performed on valve sizes 23, 25 and 27 in the aortic position, and 29, 31 and 33 in the mitral position. A wide variation was observed in mean pressure gradient and calculated orifice area in both valve types within all sizes in both the aortic and the mitral positions. In the aortic position, the Björk-Shiley prosthesis tended to have a lower pressure gradient and larger calculated orifice area than the Hancock heterograft, but the differences in gradient between the two valve types were significant only in the larger-sized valves. The difference in calculated area between the two valve types was not significant within each valve size. In the mitral position, there were no differences in gradient and calculated orifice area between the two types of prostheses. The postoperative cardiac index, regurgitant volume, pulmonary artery systolic and mean pressures, left ventricular end-diastolic pressure, left ventricular ejection fraction and left ventricular end-diastolic volume index did not differ in patients receiving the Björk-Shiley prosthesis from values in patients receiving the Hancock heterograft. Hence, the overall hemodynamic performance of both types of valves is remarkably similar. The choice between these two prostheses should, therefore, be governed not by the hemodynamic performance, but by other factors such as valve durability, risk of anticoagulation and incidence of valve-related complications.


Immunoglobulin gene expression in umbilical cord blood-derived CD34⁺ hematopoietic stem/progenitor cells.
Recently, immunoglobulin (Ig) expression was reported in a variety of non-B lineage cells, including myeloid cells. We assessed whether hematopoietic stem/progenitor cells (HSC/HPCs) can express Ig. With Gene Expression Omnibus (GEO) microarray database analysis, we found that IGHM was expressed with the highest frequency and level in umbilical cord blood CD34(+) HSC/HPCs, followed by IGK@, IGHE, IGHD, IGHG1, and IGHA1, while IGL@ was nearly not expressed. Ig expression was further confirmed by molecular experiments and immunofluorescence. Moreover, HSC/HPCs-derived Ig displayed restricted/biased usages and VHDJH rearrangement patterns. These results suggest that Igs, especially IgM, may have a role in CD34(+) HSC/HPCs function.


[The effects of subgingival irrigation with antimicrobial agents on periodontal disease].
This report evaluates the role of local pharmacotherapy by subgingival irrigation to enhance clinical and microbiological periodontal status. This kind of chemical therapy is not a substitute to scaling and root planing, but possibly could increase its beneficial effects.


An improved biofilter to control the dissolved organic nitrogen concentration during drinking water treatment.
Dissolved organic nitrogen (DON) is a key precursor of numerous disinfection by-products (DBPs), especially nitrogenous DBPs (N-DBPs) formed during disinfection in drinking water treatment. To effectively control DBPs, reduction of the DON concentration before the disinfection process is critical. Traditional biofilters can increase the DON concentration in the effluent, so an improved biofilter is needed. In this study, an improved biofilter was set up with two-layer columns using activated carbon and quartz sand under different influent patterns. Compared with the single-layer filter, the two-layer biofilter controlled the DON concentration more efficiently. The two-point influent biofilter controlled the DON concentration more effectively than the single-point influent biofilter. The improved biofilter resulted in an environment (including matrix, DO, and pH) suitable for microbial growth. Along the depth of the biofilter column, the environment affected the microbial biomass and microbial activity and thus affected the DON concentration.


Wavy Whiskers in Wakes: Explaining the Trail-Tracking Capabilities of Whisker Arrays on Seal Muzzles.
Seals can detect prey up to 180 m away using only their flow-sensing whiskers. The unique undulating morphology of Phocid seal whiskers reduces vortex-induced vibrations (VIVs), rendering seals highly sensitive to biologically relevant flow stimuli. In this work, digital models of harbor and grey seal whiskers are extracted using 3D scanning and a mathematical framework that accurately recreates their undulating geometry is proposed. Through fluid-structure interaction studies and experimental investigations involving a whisker array mounted on 3D-printed microelectromechanical systems sensors, the vibration characteristics of the whisker array and the interaction between neighboring whiskers in steady flows and fish-wake-like vortices are explained for the first time. Results reveal that the downstream vortices intensity and resulting VIVs are consistently lower for grey than harbor seal whiskers and a smooth cylinder, suggesting that the grey seal whisker geometry can be an ideal template for the biomimetic design of VIV-resistant underwater structures. In addition, neighboring whiskers in an array influence one another by resulting in greater flow vorticity fluctuation and distribution area, thus causing increased vibrations than an isolated whisker, which indicates the possibility of a signal-strengthening effect in whisker arrays.


Preoperative prediction of late cancer-specific deaths in patients with rectal and rectosigmoid carcinoma.
The possibility of predicting late cancer-specific deaths from (a) the preoperative serum levels of three tumour markers, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and an antigen defined by the C-50 antibody (CA-50), from (b) one clinical factor of independent prognostic relevance, polypoid tumour growth, and from (c) Dukes' stage was evaluated in 276 patients with rectal carcinoma operated upon with curative intent ("potentially curable"), and in the 251 of those patients who were considered to be "potentially cured" after surgery. Using the Cox regression model, the preoperative serum levels of the tumour markers strongly predicted the cancer-specific mortality within the first year after surgery. This ability of S-CEA and S-CA-50 diminished for the mortality during the second year after surgery, and virtually disappeared thereafter. The ability of S-TPA to predict cancer-specific deaths did not change as dramatically with time as that of the other two markers, particularly in the group of "potentially cured" patients. Patients with polypoid tumour growth had a good prognosis which did not appear to change with time. Similarly, the prognostic information provided by Dukes' staging system was valid at all studied time intervals after surgery, although it declined after the second year. The importance of these results in relation to the selection of patients for adjuvant treatment is discussed.


Pharmacological characterization of benzodiazepine receptors in the brain.
Receptors in rat brain membranes which specifically bind 3H-diazepam were characterized pharmacologically using reference substances representing several pharmacological classes of drugs. Of 28 benzodiazepines tested, several "classical" ones (diazepam, clonazepam, lorazepam, oxazepam, nitrazepam, flurazepam, bromazepam and chlorazepate) with known clinical efficacy, as well as three newer "triazolo" benzodiazepines (estazolam, U 35,005, U 31,957), one new "imidazolo" benzodiazepine, U 31,219, and one new 2-carbamoylmethylene-benzodiazepine, displaced 3H-diazepam binding at low concentrations (Ki=1--60 nM). For these benzodiazepines there was a stastically significant correlation between Ki values for displacement and ED50 (or MED) values in several pharmacological tests predictive of anxiolytic activity in man. More than 100 nonbenzodiazepines, representing 22 distinct pharmacological classes as well as 14 presumed neurotransmitters in the CNS, including 4 peptides, were much weaker as 3H-diazepam displacers (K2 greater than 0.1 nM). These results suggest that in vitro 3H-diazepam binding represents the physiologically relevant binding to hitherto unknown receptors in the CNS.


Hydrogen transfer by NADPH-dependent reductases in elongation of very-long-chain saturated and polyunsaturated fatty-acyl-CoA in swine cerebral microsomes.
The hydrogen transfer from NADPH was studied in the elongation of arachidoyl-CoA (20:0-CoA) and arachidonoyl-CoA (20:4-CoA) in swine cerebral microsomes. Previously, we showed that four deuterium atoms (2H) were transferred stereospecifically from (4S)-[4-2H1]NADPH in the elongation of 20:0-CoA to 24:0 (Yoshida, S., Takeshita, M. and Kawaguchi, A. (1984) Biochem. Biophys. Res. Commun. 124, 322-328), and that three deuterium atoms were transferred from 2H2O in the elongation of 20:4-CoA to 22:4. The deuteride transfer from (4S)-[4-2H1]NADPH was observed in the elongation of 20:4-CoA to 24:4, by the technique of mass fragmentography using the chemical ionization method, and, in this case, two 2H were transferred to 24:4. No deuteride was transferred from (4R)-[4-2H1]NADPH in the elongation of 20:0-CoA and 20:4-CoA. Moreover, the condensation product (3-keto-fatty-acyl-CoA) which was formed in the elongation without NADPH could be reduced by the addition of NADPH and sodium hydrosulfite, for the elongation of 16:0-CoA and 20:4-CoA, while the condensation product from 20:0-CoA could be reduced only by NADPH, but not by hydrosulfite. The hydrosulfite did not produce the final elongation products from 20:0-CoA, 16:0-CoA or 20:4-CoA. These results suggested that the hydride was transferred from NADPH stereospecifically only in the elongation of 20:0-CoA in the step of 3-ketoacyl-CoA reduction by the reductase which might be different from that for the elongation of 16:0-CoA and 20:4-CoA in which the proton exchange might occur via a water proton in the reduction of 3-ketoacyl-CoA. Accordingly, the hydride transfer might occur from NADPH in the step of 2,3-enoyl reduction in the elongation of 20:0-, 16:0- and 20:4-CoA.


Knowledge, attitude, and practice toward regenerative endodontics and factors affecting its practice among dental practitioners in Ajmer city: A cross-sectional study.
Regenerative methods, which regenerate the damaged structures, are one of the treatment methods in endodntics. This conservative approach helps to generate cells that may produce the lost structure. Thus, the aim of this study was to explore the knowledge, attitude, and practice among dental practitioners toward regenerative endodontics and factors affecting their knowledge, attitude, and practice. It was a cross-sectional questionnaire study conducted in the month of June-August 2018 in Ajmer city. Permission to conduct the study was obtained from JLN Medical College and Hospital, Department of Dentistry. A total of 100 clinics were visited and face-to-face interview schedule was conducted. A total of 123 dental practitioners were interviewed. A 26 item questionnaire was generated to measure knowledge, attitude, and practice of dental professionals regarding regenerative endodontics. 63% of study participants had poor knowledge scores. Majority of study participants 83 (67%) had poor attitude scores. On applying Pearson's correlation, it was determined that the knowledge regarding regenerative endodontics was significantly (P ≤ 0.001) ** correlated to the attitude among study participants. On applying Chi-square test, it was assessed that the knowledge and practice among study participants were significantly (P = 0.041*) and (P = 0.001**) associated with gender of study participants. From above results, it is concluded that study participants have poor knowledge, attitude, and practice regarding regenerative endodontics. The knowledge regarding regenerative endodontics was significantly associated with the attitude of study participants. Participants with Masters of Dental Surgery (MDS) degree had a significant effect on the knowledge regarding the regenerative endodontics. Endodontic specialty has a significant effect on the attitude of study subjects.


Pharmacologic reduction of angiographic vasospasm in experimental subarachnoid hemorrhage: systematic review and meta-analysis.
Animal models have been developed to simulate angiographic vasospasm secondary to subarachnoid hemorrhage (SAH) and to test pharmacologic treatments. Our aim was to evaluate the effect of pharmacologic treatments that have been tested in humans and in preclinical studies to determine if animal models inform results reported in humans. A systematic review and meta-analysis of SAH studies was performed. We investigated predictors of translation from animals to humans with multivariate logistic regression. Pharmacologic reduction of vasospasm was effective in mice, rats, rabbits, dogs, nonhuman primates (standard mean difference of -1.74; 95% confidence interval -2.04 to -1.44) and humans. Animal studies were generally of poor methodologic quality and there was evidence of publication bias. Subgroup analysis by drug and species showed that statins, tissue plasminogen activator, erythropoietin, endothelin receptor antagonists, calcium channel antagonists, fasudil, and tirilazad were effective whereas magnesium was not. Only evaluation of vasospasm >3 days after SAH was independently associated with successful translation. We conclude that reduction of vasospasm is effective in animals and humans and that evaluation of vasospasm >3 days after SAH may be preferable for preclinical models.


The stability of transcription factor PfSPL1 participates in the response to phytoplasma stress in Paulownia fortunei.
The current understanding of the pathogenesis of phytoplasma is still very limited and challenging. Here, ceRNA regulatory network and degradome sequencing identified a PfmiR156f-PfSPL regulatory module in Paulownia fortunei infected by phytoplasma, and RLM-5'RACE and dual luciferase analyses verified the relationship. The PfmiR156 cleavage site was located at 1104 nt and 1177 nt of PfSPL1 and PfSPL10, respectively. MG132 and epoxomicin, two 26S proteasome inhibitors, significantly increased the accumulation of PfSPL1. PfSPL1 was also the attack target of phytoplasma effectors (Pawb 3/9/16/37/51) after the phytoplasma invaded Paulownia. Moreover, molecular docking implied that the effectors may interact with the conserved SBP domain of the target protein PfSPL1. Basically, these results indicated that the stability of PfSPL1 was regulated by PfmiR156 cleavage activity and/or the 26S proteasome pathway at the post-translation level. The PfSPL1, which is a transcription factor, was also the one of the targets of multiple effectors attacking Paulownia. This study provides a good scope to understand the paulownia phytoplasma infecting mechanism.


Spontaneous calcaneal fracture after deep heel burns with diabetes.
Two patients with diabetes mellitus sustained spontaneous calcaneus fracture after deep heel burns. Both cases had avulsion type fracture of the os calcis. The authors discuss the incidence and possible etiology with literature review.


Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.
There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration. The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo. CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment. Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites. This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.


Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment.
The polycomb complex protein BMI-1 (BMI-1) is a putative oncogene reported to be overexpressed in multiple myeloma (MM). Silencing of BMI-1 was shown to impair the growth and survival of MM cells. However, therapeutic agents specifically targeting BMI-1 were not available so far. Here, we investigated PTC-209, a novel small molecule inhibitor of BMI-1, for its activity in MM. BMI-1 expression was analysed in human MM cell lines and primary MM cells by using publically available gene expression profiling (GEP) data. The anti-MM activity of PTC-209 was investigated by viability testing, cell cycle analysis, annexin V and 7-AAD staining, quantification of cleaved poly(ADP-ribose) polymerase (PARP), JC-1 as well as colony formation assays. Deregulation of central myeloma growth and survival genes was studied by quantitative PCR and flow cytometry, respectively. In addition, the impact of PTC-209 on in vitro osteoclast, osteoblast and tube formation was analysed. We confirmed overexpression of BMI-1 in MM patients by using publically available GEP datasets. Of note, BMI-1 expression was further increased at relapse which translated into significantly shorter overall survival in relapsed/refractory patients treated with bortezomib or dexamethasone. Treatment with PTC-209 significantly decreased viable cell numbers in human MM cell lines, induced a G1 cell cycle arrest, promoted apoptosis and demonstrated synergistic activity with pomalidomide and carfilzomib. The anti-MM activity of PTC-209 was accompanied by a significant decrease of cyclin D1 (CCND1) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) expression as well as upregulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) and cyclin-dependent kinase inhibitor 1B (CDKN1B). We also observed upregulation of NOXA (up to 3.6 ± 1.2-fold induction, P = 0.009) and subsequent downregulation of myeloid cell leukemia 1 (MCL-1) protein levels, which likely mediates the apoptotic effects of PTC-209. Importantly, the anti-MM activity was upheld in the presence of stromal support or myeloma growth factors insulin-like growth factor 1 (IGF-1) and interleukin 6 (IL-6). In the MM microenvironment, PTC-209 impaired tube formation, impaired osteoclast development and decreased osteoblast formation in a dose-dependent manner (P < 0.01 at 1 μM, respectively). The latter might be attributed to an induction of DKK1 and was reversed by concurrent anti-DKK1 antibody treatment. We confirmed overexpression of BMI-1 in MM highlighting its role as an attractive drug target and reveal therapeutic targeting of BMI-1 by PTC-209 as a promising novel therapeutic intervention for MM.


A systematic review of the clinical effectiveness of emergency endovascular therapy using mechanical thrombectomy in acute ischaemic stroke: implications for service delivery.
Twelve randomised controlled trials (RCTs) comparing mechanical thrombectomy against traditional treatment options for patients experiencing acute ischaemic stroke (AIS) have been published. To evaluate whether this technology is more effective and/or safer than traditional treatment options and to assess the potential for implementation of this technology as a treatment strategy for acute ischaemic stroke in Ireland. RCTs published up to February 2017 were included. Meta-analysis was performed for two primary (mortality at 90 days, mRS at 90 days) and four secondary outcomes. Cumulative meta-analysis was used to investigate the point at which a consistent treatment effect was observed for outcomes that had a statistically significant pooled effect. Mechanical thrombectomy was associated with higher likelihood of being independent (mRS, p < 0.01; Barthel index, p < 0.01) at 90 days post-AIS (p < 0.001). Cumulative meta-analysis demonstrated a consistent treatment effect in favour of mechanical thrombectomy after each trial was added to the analysis. There was no evidence of a difference in mortality rates (p = 0.21) or rates of SICH (p = 0.71) between patients randomised to intervention and control arms. Although the intervention appears to be associated with higher rates of any cerebral haemorrhage (p < 0.01) and recurrent ischaemic stroke (p = 0.03), considerable uncertainty remains as to these treatment effects. The trials published most recently have acted as a 'watershed' for mechanical thrombectomy, and while there are significant caveats, the data suggests that mechanical thrombectomy needs to be factored into the planning and delivery of services for the management of patients with acute ischaemic stroke in Ireland.


High expression of GCLC is associated with malignant melanoma of low oxidative phenotype and predicts a better prognosis.
Reactive oxygen species (ROS) are strongly implicated in melanoma development, and treatment with antioxidants has shown efficacy in suppressing malignant transition and progression. Here, we investigated the significance of the glutamate-L: -cysteine ligase catalytic subunit (GCLC) expression, a key regulator of glutathione synthesis, for malignant melanoma. A large set of melanoma cell lines (n = 36) was analyzed, and higher GCLC levels were associated with lower presence of intracellular ROS and interestingly also lower rates of cell proliferation. Moreover, treatment with the antioxidant N-acetylcysteine efficiently reduced the growth speed of several investigated malignant cells. In addition GCLC expression was significantly linked to a prominent set of cellular antioxidants, accounting for the observed lower basal levels of oxidative stress and higher antioxidative capacity. Key attributes defining the malignant phenotype of melanoma cells including survival, invasiveness, and switch from E-cadherin to N-cadherin expression were more prominent in cells with lower GCLC expression. Our findings were further corroborated by observations in Rag2(-/-)γc(-/-)mice, in which melanoma cells with lower GCLC expression depicted a dramatically stronger tumor growth. Furthermore, prognostic significance of GCLC expression was investigated in patients (n = 28) with advanced malignant melanoma. High tumor immunoreactivity for GCLC was a significant determinant for better 5-year overall survival. Conclusively, we show for the first time that GCLC may serve a dual role, as a surrogate marker for cellular redox state as well as malignant potential of melanoma cells. These promising results regarding its prognostic significance as well as its potential as a pharmacological target require further in-depth investigations.


Origins of the American Board of Thoracic Surgery.
With the establishment of its own certifying board in 1948, thoracic surgery finally began to be accepted as a full-fledged medical specialty. A founding member of the American Board of Thoracic Surgery traces its historical and medical roots and recalls the philosophical turmoil of its early days.


Tracheobronchial injuries after blunt chest trauma in children--hidden pathology.
Blunt thoracic injuries in children are unique because the pliability of the chest wall allows transmission of massive external force directly into the mediastinum. Children presenting after blunt chest trauma may have complete disruption of the airway with little external sign of injury. Without prompt diagnosis and appropriate treatment, the risk for progressive respiratory failure is high. Four children with tracheobronchial injuries were referred to a pediatric trauma center from 1994 to 1997. All children, age 18 months to 13 years, suffered unusual crush injuries. All diagnoses were based on unresolved pneumothorax or pneumomediastinum. Bronchoscopy identified the location of injury as posterior trachea (n = 1) and right mainstem bronchus (n = 2). A tertiary bronchial injury (n = 1) was missed by initial tracheogram and subsequent bronchoscopy but identified during surgical exploration. All children survived after thoracotomy and primary repair of the injury. Tracheobronchial disruption is a rare, life-threatening injury. Suspicion should be high when pneumomediastinum and pneumothorax are refractory to adequate pleural drainage. Flexible bronchoscopy with intubation distal to the injury may be necessary to prevent loss of the airway. Advance preparation should include setups for bronchoscopy, thoracotomy, and cardiopulmonary bypass. Patient survival depends on preparation and prompt surgical intervention.


Transiently increased serotonin has modest or no effects on bone mass accrual in growing female C57BL6/J or growing male and female Lrp5A214V mice.
Serotonin (5HT) is a chemical messenger with biologic activities affecting multiple organs. Within the skeletal system, studies in mice and humans suggest blood 5HT levels affect bone, with elevations impairing and reductions enhancing bone accrual. Other studies, however, have not supported this hypothesis. Recently, administering 5HT to a Piezo1 mutant mouse strain with hyposerotonemia, intestinal dysmotility, and a doubling of femoral trabecular bone mass at 2 months of age, was reported to return the animals' intestinal motility and bone mass to normal. However, whether the 5HT directly affected bone metabolism or indirectly affected metabolism by improving intestinal function was not determined. Therefore, we administered 5HT to mice with normal intestinal function. We randomized female C57BL6/J mice and male and female mice that have increased bone mass due to a missense mutation in the WNT co-receptor LRP5 (Lrp5A214V) to receive 5HT or vehicle via daily IP injection from 4 weeks to 8 weeks of age. We did not observe consistent significant changes for distal femur trabecular, midshaft femur cortical, or vertebral body trabecular bone mass between 5HT treated and vehicle treated mice of either genotype. These data are compatible with other studies that have not observed a correlation between blood 5HT level and bone mass.


Modelling of the near-field of metallic nanoparticle gratings: localized surface plasmon resonance and SERS applications.
We numerically study the influence of the shape of gold nanostructures on the spectral position of their localized surface plasmon resonance and on Surface Enhanced Raman Scattering efficiency. Calculations are performed using a Finite-Difference Time-Domain (FDTD) method, whose accuracy for dispersive media is enhanced through the use of a Drude-Lorentz model. The relevance of this method is then pointed out by comparing the calculations with experimental data for both the plasmon resonance and the Raman signal enhancement. The influence of a thin layer of water is also investigated.


Conserved functions of RNA-binding proteins in muscle.
Animals require different types of muscle for survival, for example for circulation, motility, reproduction and digestion. Much emphasis in the muscle field has been placed on understanding how transcriptional regulation generates diverse types of muscle during development. Recent work indicates that alternative splicing and RNA regulation are as critical to muscle development, and altered function of RNA-binding proteins causes muscle disease. Although hundreds of genes predicted to bind RNA are expressed in muscles, many fewer have been functionally characterized. We present a cross-species view summarizing what is known about RNA-binding protein function in muscle, from worms and flies to zebrafish, mice and humans. In particular, we focus on alternative splicing regulated by the CELF, MBNL and RBFOX families of proteins. We discuss the systemic nature of diseases associated with loss of RNA-binding proteins in muscle, focusing on mis-regulation of CELF and MBNL in myotonic dystrophy. These examples illustrate the conservation of RNA-binding protein function and the marked utility of genetic model systems in understanding mechanisms of RNA regulation.


Expression of a structural domain of the beta 2 subunit essential for alpha M beta 2 ligand recognition.
The beta2 leukocyte integrins comprise a group of closely related adhesion receptors that mediate critical events during normal and inflammatory immune responses. Central to the understanding of beta2 integrin function is the basis of ligand recognition. Results from our laboratory and others indicate the presence of multiple ligand contact points in both the alpha and beta subunit. As an approach to identify and characterize regulatory domains of the beta2 subunit, we have generated two different subdomains of the beta2 subunit for expression on the surface of mammalian cells through a phosphatidyl-inositol glycan anchor. The first subdomain contains the putative beta2 MIDAS motif implicated in ligand binding [beta2(LB)], whereas the second beta2 subdomain contains the cysteine-rich region [beta2(CR)]. Cells expressing alphaM and beta2 constructs singly or cotransfected transiently in COS-7 cells were tested for the ability to bind to immobilized iC3b. Cells bearing the recombinant alphaMbeta2(LB) were capable of adhering to iC3b in a manner similar to that observed with the complete alphaMbeta2 heterodimer. In contrast, cells expressing alphaMbeta2(CR) failed to adhere to immobilized iC3b. Moreover, cells bearing singly transfected alpha or beta chains alone failed to adhere to immobilized iC3b. These results indicate that along with alphaM, the beta2(LB) subdomain contains the sufficient components within the beta2 subunit essential for ligand recognition. These findings support the hypothesis that the beta2 subunit cooperates with site(s) within the alphaM subunit in a receptor/cation/ligand complex resulting in high-affinity ligand interaction.


Purification and some characteristics of nitric oxide reductase-containing vesicles from Paracoccus denitrificans.
Nitric oxide reductase of Paracoccus denitrificans was purified, with the use of 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate (CHAPSO) detergent, as membrane vesicles of apparent Mr = 2-3 x 10(6). Fifty percent of the protein was a peptide of Mr = 34,000. Further fractionation with sodium dodecyl sulfate (SDS) resulted in vesicles in which the peptide constituted 90-95% of the protein. This peptide, which is rich in Ala, Gly, Ser, Asx, and Glx, is considered to be the peptide of nitric oxide reductase. The CHAPSO- and SDS-fractionated preparations lost activity at 4 degrees C, pH 7.4, with half-times, respectively, of about 6 days and 4 h. Specific activities at 32 degrees C, pH 7.4, of about 0.33 mumol of NO x min-1 x mg-1 were realized after fractionation with CHAPSO in a phenazine methosulfate/ascorbate-based assay. The Km(NO) was less than or equal to 17 microM at pH 7.4. Rates decreased substantially below pH 5 and above pH 7.6. The preparations were free or almost free of cytochromes, exhibited otherwise no absorption bands in the visible region, contained no redox metals except for very small amounts of iron, were not inhibited by EDTA or some other common inhibitors of redox-metal enzymes, and were not observed to catalyze the reduction of nitrate, nitrite, or N2O. An absorption band at 274 nm in both the CHAPSO- and SDS-fractionated preparations was attributed to the presence of a solvent-soluble chromophore. N-Bromosuccinimide (NBS) inactivated the enzyme and bleached the chromophore both in the enzyme preparation and, after its purification, in 95% ethanol. NBS-inactivated enzyme could be reconstituted with purified chromophore, which alone seemed to have no nitric oxide reductase activity, but not with purified chromophore that had been reacted with NBS. Spectral changes interpretable as due to changes in redox state were not observed when enzyme was exposed to NO or certain reducing agents.


[Podocytopathie and transdifferentiation of the podocytes in human glomerulonephritis. An immunomorphological study].
Transdifferentiation is characterized by a loss of normal epitopes by differentiated cells, accompanied by the acquisition of new epitopes and new functions. Podocytes are differentiated epithelial cells that cover and adhere to the outer surface of the glomerular basement membrane (GBM). The podocyte/GBM complex contributes to the selective filter function of the glomerular tuft. We have shown that, in various human glomerulonephritides, "dysregulated" podocytes acquire the potential to proliferate and multiply, undergo profound morphologic changes, detach from the GBM, and show phenotypic changes indicative of transdifferentiation. In the course of these events they lose their original epitopes and acquire macrophagic markers.


Risk of SARS-CoV-2 transmission to medical staff and patients from an exposure to a COVID-19-positive ophthalmologist.
To evaluate the risk of transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after exposure to a COVID-19+ physician in a retina clinic. A retrospective observational study. Records of 142 patients and 11 staff members from a single retina clinic that were exposed to a COVID-19+ ophthalmologist were reviewed. All 153 individuals were placed in quarantine for 14 days. They were contacted after the quarantine period to inquire about symptoms consistent with COVID-19, and the results of diagnostic test for SARS-CoV-2 when performed. All patients (n = 142) were contacted successfully. The mean age was 72.8 ± 13.6 years; 54.2% (n = 77) were females. Twenty-three patients (16.2%) were exposed during an ophthalmic exam, 111 (78.2%) during intraocular injection, 4 (2.8%) underwent exam and injection, 3 (2.1%) underwent surgery, and one patient (0.7%) had laser photocoagulation. Half of the patients (50%; n = 71) were in contact with the COVID-19+ physician while he was symptomatic. Forty-four patients (31%) wore a mask on the day of their visit. 11.3% (n = 16) of the patients, and all involved staff had been tested for the virus and all were negative. One patient (0.7%) reported transient cough and sore throat, and the remaining 141 (99.3%) patients and 11 (100%) staff did not develop symptoms. Low risk for SARS-CoV-2 transmission in the ophthalmic setting was observed when universal safety measures such as social distancing, meticulous hand hygiene, enlarged breath shields, and mask wear during procedures were taken.


eHealth in Europe - Status and Challenges.
To present European reflections on the concept of eHealth and emerging challenges related to further development of eHealth in Europe. A survey with 10 questions was distributed to representatives of the national member associations of the European Federation of Medical Informatics (EFMI). The results document a shift from a constricting ICT-orientation to development of the entire health system where eHealth strategies, organizational change, and appropriate technological infrastructure are singled out as important aspects. There are urgent needs to ensure that eHealth strategies and policies for further design and deployment of eHealth applications support sociable services and innovations in health care.


Arthroscopic Bankart Repair for the Management of Anterior Shoulder Instability: Indications and Outcomes.
Arthroscopic Bankart repair is commonly utilized for shoulder stabilization in patients with anterior shoulder instability with minimum glenoid bone loss. The purpose of this review is to provide the indications, surgical technique, complications, and recent outcomes in arthroscopic Bankart repair for shoulder instability. Improvements in arthroscopic techniques have led to better patient outcomes, as well as an improved understanding of the pathoanatomy of instability. More recent studies have shown that one of the potential failures of primary arthroscopic repair may be due to unaddressed bone loss. This underscores the importance of evaluating glenoid bone loss and proper patient selection for this procedure to ensure successful outcome. When indicated, arthroscopic stabilization is the treatment of choice for many surgeons due to its lower morbidity and low overall complication rate. Future work must focus on longer-term outcomes in patients undergoing arthroscopic Bankart repair, as well as the clinical outcomes of new fixation techniques, augmentation techniques, and the effect of glenoid bone loss in outcome.


Assessing the capacity to diagnose human African trypanosomiasis among health care personnel from Chama and Mambwe districts of eastern Zambia.
Human African Trypanosomiasis (HAT) is a neglected tropical disease affecting poor rural communities living in tsetse-infested regions of sub-Saharan Africa. In Zambia, sporadic cases of HAT have been reported mainly in the old foci along the tsetse-infested Luangwa river valley in north-eastern part of the country. In such places where malaria is the major endemic febrile disease, with possibilities of co-infections of HAT and malaria and where the levels of alertness to the presence of HAT among health care personnel (HCP) is low, there is a high chance of misdiagnosing HAT for malaria because of their similarities in clinical presentation. This study, conducted in Zambia's tsetse-infested rural health centres (RHCs) of Chama and Mambwe districts, was designed to investigate the staffing levels, the HCP levels of alertness to the occurrence of HAT and their capacity to detect the disease. Structured questionnaires were used to collect information pertaining to HAT alertness and the capacity to detect the disease from 101 HCP in a cross sectional study of 23 RHCs drawn from Zambia's Chama and Mambwe districts between April and July 2013. The data collected were analyzed using Stata/SE version 11.0. Participants from both Chama and Mambwe district RHCs reported similar very low levels of qualified HCP and laboratory technicians, and that they had similar basic tools for HAT diagnosis. Although not statistically significant, respondents from Chama (~89%) tended to be more aware about the occurrence of HAT compared to their Mambwe counterparts (~78%). Whereas ~40% of the HCP from Chama district (n = 52) claimed to have encountered at least one case of HAT, only ~4% of their Mambwe counterparts (n = 49) had similar experiences (P = 0.000). Health care personnel in RHCs from Chama tended to be more alert to the occurrence of HAT than the HCP from Mambwe district. The extremely low levels of categorized HCP, general absence of functional laboratories, coupled with absence of national HAT surveillance and control programs, are among some of the serious challenges that Zambia's Chama and Mambwe districts face to control/eliminate HAT.


Case report: Aborted sudden cardiac death as a first presentation of severe mitral annulus disjunction-a case series and review of the literature.
Mitral annulus disjunction (MAD) is defined as a systolic displacement between the ventricular myocardium and the posterior mitral annulus supporting the posterior mitral leaflet. This structural abnormality is associated with the loss of mechanical annular function manifested as an abnormal systolic excursion of the leaflet hinge point into the left atrium but with maintained electrical function, separating the left atrium and ventricle electrophysiologically. The mitro-aortic fibrous continuity limits MAD anteriorly, between the aortic cusps and the anterior leaflet of the mitral valve. Consequently, MAD has been observed only at the insertion of the posterior leaflet. It can extend preferentially at the central posterior scallop. The first diagnostic modality aiding the diagnosis is transthoracic echocardiography (TTE), although in some cases adjunctive cardiac imaging modality might be suggested. MAD carries a strong association with malignant ventricular arrhythmogenesis and a profound predisposition for sudden cardiac death (SCD). In this context, a thorough investigation of this morphological and functional abnormality is vital in estimating the risk assessment and stratification for optimal management and elimination of the risk of the patient for SCD. Based on the current scientific data and literature, we will discuss the diagnosis, clinical implications, risk stratification, and therapeutic management of MAD.


Investigation of the support constraint effect and failure instability law of tunnels constructed using the New Austrian tunneling method.
The application of a reasonable numerical calculation method is the key to accurately analyzing tunnel rock-support interactions. In this paper, we address the support constraint effect of tunnels and analyze the influence of related factors based on the confinement convergence method. Rupturable support models are developed using FLAC3D to intuitively show the numerical calculation results of tunnels. The results imply that the virtual supporting force generated by the support constraint effect should be considered in two-dimensional rock tunnel model calculations, and that the supporting force of the support should be increased by 2-3% of the maximum supporting force. Boundary effects should be considered in the three-dimensional tunnel model calculations, in which the influence range of the model boundary effect is nearly 1.5 times the tunnel span. A comparison of the field monitoring data and numerical calculations of the Baoshan tunnel project shows that the numerical results that consider the support constraint effect are in better agreement with the actual project situation. The rupturable support models can also reflect the stress and failure evolution law of supports, and provide support for the accurate evaluation of tunnel engineering stability.


The influence of gene-environment interactions on the development of alcoholism and drug dependence.
Alcoholism and drug dependence are common psychiatric disorders with a heritability of about 50%; therefore genetic and environmental influences are equally important. Early-life stress is a predictor of adolescent problem drinking/drug use and alcohol/drug dependence in adulthood, but moderating factors governing the availability of alcohol/drug are important. The risk-resilience balance for addiction may be due in part to the interaction between genetic variation and environment stressors (G × E); this has been confirmed by twin studies of inferred genetic risk. Measured genotype studies to detect G × E effects have used a range of alcohol consumption and diagnostic phenotypes and stressors ranging from early-life to adulthood past year life events. In this article, the current state of the field is critically reviewed and suggestions are put forth for future research.


Physical fitness and maternal body composition indices during pregnancy and postpartum: the GESTAFIT project.
We explored the association of physical fitness (PF) during pregnancy with maternal body composition indices along pregnancy and postpartum period. The study comprised 159 pregnant women (32.9 ± 4.7 years old). Assessments were carried out at the 16th and 34th gestational weeks (g.w.) and six weeks postpartum. Cardiorespiratory fitness (CRF), muscular strength (absolute and relative values) and flexibility were measured. Body composition indices were obtained by using dual-energy X-ray absorptiometry at postpartum. The results, after adjusting for potential covariates at the 16th g.w., indicated that greater CRF was associated with lower postpartum indices total fat mass, android and gynoid fat mass (all, p < 0.05). Greater absolute upper-body muscular strength was associated with greater pre-pregnancy body mass index (BMI), gestational weight gain (GWG); and postpartum indices body weight, BMI, lean mass, fat free mass, fat mass, gynoid fat mass, T-score and Z-score bone mineral density (BMD) (all, p < 0.05). Greater upper-body flexibility was associated with lower pre-pregnancy BMI; and postpartum indices body weight, BMI, lean mass, fat free mass, fat mass, android fat mass and gynoid fat mass, and with greater GWG (all, p < 0.05). At the 34th g.w., greater CRF was additionally associated with greater postpartum T-score and Z-score BMD (both, p < 0.05). In conclusion, this study reveals that greater PF levels, especially during early pregnancy, may promote a better body composition in the postpartum period. Therefore, clinicians and health promoters should encourage women to maintain or improve PF levels from early pregnancy.


Slow-binding inhibition of NAD+ glycohydrolase by arabino analogues of beta-NAD.
Modifications at the 2'-position of the nicotinamide-ribosyl moiety influence dramatically the nature of the interactions of the modified beta-NAD+ with calf spleen NAD+ glycohydrolase (EC 220.127.116.11), an enzyme that cleaves the nicotinamide-ribose bound in NAD(P)+. Nicotinamide arabinoside adenine dinucleotide (ara-NAD+) and nicotinamide 2'-deoxy-2'-fluoroarabinoside adenine dinucleotide (araF-NAD+) are not hydrolyzed at measurable rates and are the first documented examples of reversible slow binding inhibitors of this class of enzyme. The kinetic data obtained are consistent with both slow kon and koff rate constants in the formation of an enzyme-inhibitor complex, i.e. the association rate constants are about 10(4) and 10(6) slower than diffusion rates, respectively, for araF-NAD+ and ara-NAD+, and the half-life of the complex is about 3-10 min for both analogues. The kinetic model does not account for a slow turnover of an ADP-ribosyl-enzyme intermediary complex. AraF-NAD+ is one of the most potent inhibitors described for NAD+ glycohydrolase.


WOMAC-pf as a measure of physical function in patients with Parkinson's disease and late-onset sequels of poliomyelitis: unidimensionality and item behaviour.
To assess psychometric properties of the Western Ontario and MacMasters Universities Osteoarthritis Index (WOMAC)-pf, an osteoarthritis (OA)-specific questionnaire used to establish the level of physical functioning in patients with late-onset sequels of poliomyelitis (LOSP) and Parkinson's disease (PD). Unidimensionality (using principal component analyses [PCA] and Rasch analyses) was separately established for three diagnostic groups: OA (n = 288), LOSP (n = 168) and PD (n = 200). Additionally, differential item functioning (DIF) among the three diagnostic groups was assessed using ordinal regression (Polytomous Universal Model) analyses. Baseline data were used from an ongoing cohort study of these three patient populations. Unidimensionality was adequate, with all items loading on the first principal component. The Rasch analyses revealed that item fit was generally good. Uniform and non-uniform DIF were found to be present among the three diagnostic groups in three and one of the 17 physical functioning subscale (WOMAC-pf) items, respectively. The WOMAC-pf is a unidimensional measure of physical functioning in patients with LOSP and PD, in addition to its established use in OA. [ • Disability in physical functioning related to mobility(walking, stair climbing, etc.) is a common feature of many chronic diseases, including osteoarthritis, late-onset sequels of poliomyelitis and Parkinson's disease.• In this study, the Western Ontario and MacMasters Universities Osteoarthritis Index-pf was shown to bea useful and adequate tool to assess physical functioning in these patient groups.• The study highlighted that, despite differences in diagnosis,history and course of the disease, patients with different conditions experience similar disabilities in their physical functioning.]


[DISTENDED FETAL BLADDER].
Distended fetal bladder, also known as fetal megacystis, usually points to lower urinary tract obstruction (LUTO) which is most commonly caused by posterior urethral valves (PUV) in the male fetus. We present a short case-series of fetal megacystis without oligohydramnion where primary vesicoureteral reflux (VUR) was the leading aetiology. These cases also displayed a high rate of kidney dysplasia with early-onset renal dysfunction. By contrast, late-onset diagnosis of isolated megacystis, i.e without significant renal parenchymal or upper urinary tract abnormalities, had a surprisingly benign postnatal course with spontaneous resolution after birth. Our case series also display the associated risk for extra-renal malformations and specifically neuro-cognitive developmental abnormalities which should be sought on genetic and imaging evaluation.