Epidemiology meets toxicogenomics: Mining toxicologic evidence in support of an untargeted analysis of pesticides exposure and Parkinson's disease.
Pesticides have been widely used in agriculture for more than half a century. However, with thousands currently in use, most have not been adequately assessed for influence Parkinson's disease (PD). Here we aimed to assess biologic plausibility of 70 pesticides implicated with PD through an agnostic pesticide-wide association study using a data mining approach linking toxicology and toxicogenomics databases. We linked the 70 targeted pesticides to quantitative high-throughput screening assay findings from the Toxicology in the 21st Century (Tox21) program and pesticide-related genetic/disease information with the Comparative Toxicogenomics Database (CTD). We used the CTD to determine networks of genes each pesticide has been linked to and assess enrichment of relevant gene ontology (GO) annotations. With Tox21, we evaluated pesticide induced activity on a series of 43 nuclear receptor and stress response assays and two cytotoxicity assays. Overall, 59 % of the 70 pesticides had chemical-gene networks including at least one PD gene/gene product. In total, 41 % of the pesticides had chemical-gene networks enriched for ≥ 1 high-priority PD GO terms. For instance, 23 pesticides had chemical-gene networks enriched for response to oxidative stress, 21 for regulation of neuron death, and twelve for autophagy, including copper sulfate, endosulfan and chlorpyrifos. Of the pesticides tested against the Tox21 assays, 79 % showed activity on ≥ 1 assay and 11 were toxic to the two human cell lines. The set of PD-associated pesticides showed more activity than expected on assays testing for xenobiotic homeostasis, mitochondrial membrane permeability, and genotoxic stress. Overall, cross-database queries allowed us to connect a targeted set of pesticides implicated in PD via epidemiology to specific biologic targets relevant to PD etiology. This knowledge can be used to help prioritize targets for future experimental studies and improve our understanding of the role of pesticides in PD etiology.


Cerebrotendinous xanthomatosis.
Cerebrotendinous xanthomatosis (CTX) is a familial sterol storage disease based on an inborn error of metabolism involving bile acid synthesis. Predominant clinical features are a chronic progressive neurological syndrome, mental deterioration, bilateral cataract and xanthomas. The presence of xanthomas usually leads to the diagnosis, and the reverse is probably also true: without xanthomas the diagnosis will often not be made. CTX may therefore be less rare than commonly thought, and the incidence of xanthomas in CTX may be overestimated. Four cases without xanthomas among the presenting symptoms are described, and the relevance of xanthomas in CTX is discussed.


[Alterations in two enzymes: superoxide dismutase and glutathion peroxidase in developmental infantile psychosis (infantile autism) (author's transl)].
After they gave a classification of the different circumstances under which the infantile autism can exist, the authors expose the data of their researches on the intermediate metabolism of oxygen of those children. Superoxyde dismutase I and glutathion peroxydase activities seem to be abnormal in the erythrocytes whereas only superoxyde dismutase I activity appears to be abnormal in the platelets.


Team- and task-related knowledge in shared mental models in operating room teams: A survey study.
The operating room is a highly complex environment, where patient care is delivered by interprofessional teams. Unfortunately, issues with communication and teamwork occur, potentially leading to patient harm. A shared mental model is one prerequisite to function effectively as a team, and consists of task- and team-related knowledge. We aimed to explore potential differences in task- and team-related knowledge between the different professions working in the operating room. The assessed team-related knowledge consisted of knowledge regarding other professions' training and work activities, and of perceived traits of a high-performing and underperforming colleague. Task-related knowledge was assessed by mapping the perceived allocation of responsibilities for certain tasks, using a Likert-type scale. A single sample cross-sectional study. The study was performed in three hospitals in the Netherlands, one academic center and two regional teaching hospitals. 106 health care professionals participated, of four professions. Most respondents (77%) were certified professionals, the others were still in training. Participants generally were well informed about each other's training and work activities and nearly everyone mentioned the importance of adequate communication and teamwork. Discrepancies were also observed. The other professions knew on average the least about the profession of anesthesiologists and most about the profession of surgeons. When assessing the responsibilities regarding tasks we found consensus in well-defined and/or protocolized tasks, but variation in less clearly defined tasks. Team- and task-related knowledge in the operating room team is reasonably well developed, but irregularly, with potentially crucial differences in knowledge related to patient care. Awareness of these discrepancies is the first step in further optimization of team performance.


Pharmacological actions of a new TRH analogue, YM-14673, in rats subjected to cerebral ischemia and anoxia.
The cerebral protective actions of a new thyrotropin releasing hormone (TRH) analogue, YM-14673, [Na-[[(S)-4-oxo-2-azetidinyl-carbonyl]-L-histidyl-L-prolinamide] dihydrate), were compared with those of CDP-choline (cerebral metabolic enhancer) and naloxone in rats rats subjected to unilateral carotid artery ligation and anoxic exposure (Levine rats). Drugs were administered intraperitoneally or orally 20, 80, and 140 min after anoxia. YM-14673 (0.03 to 1 mg/kg i.p. and 0.3 to 10 mg/kg p.o.) decreased the incidence of neurological deficits, such as hemiplegia and convulsion followed by coma and death, for 48 h after ischemia and anoxia. Both the increase in the brain water content and the degeneration of neurons in the cerebral cortex and thalamus were prevented by YM-14673 at a dose of 0.1 mg/kg (i.p.). CDP-choline (400 mg/kg i.p.), which is currently used in the therapy of cerebral vascular diseases, and naloxone (3 mg/kg i.p.) also decreased the incidence of the neurological deficits. These results suggest that YM-14673 protects Levine rats against neurological deficits, presumably by attenuating the development of brain edema and preventing neuronal damage. This compound may be useful in the therapeutic treatment of cerebral vascular diseases.


Supertertiary protein structure affects an allosteric network.
The notion that protein function is allosterically regulated by structural or dynamic changes in proteins has been extensively investigated in several protein domains in isolation. In particular, PDZ domains have represented a paradigm for these studies, despite providing conflicting results. Furthermore, it is still unknown how the association between protein domains in supramodules, consitituting so-called supertertiary structures, affects allosteric networks. Here, we experimentally mapped the allosteric network in a PDZ:ligand complex, both in isolation and in the context of a supramodular structure, and show that allosteric networks in a PDZ domain are highly dependent on the supertertiary structure in which they are present. This striking sensitivity of allosteric networks to the presence of adjacent protein domains is likely a common property of supertertiary structures in proteins. Our findings have general implications for prediction of allosteric networks from primary and tertiary structures and for quantitative descriptions of allostery.


Estimating the association between burnout and electronic health record-related stress among advanced practice registered nurses.
Health information technology (HIT), such as electronic health records (EHRs), is a growing part of the clinical landscape. Recent studies among physicians suggest that HIT is associated with a higher prevalence of burnout. Few studies have investigated the workflow and practice-level predictors of burnout among advanced practice registered nurses (APRNs). Characterize HIT use and measure associations between EHR-related stress and burnout among APRNs. An electronic survey was administered to all APRNs licensed in Rhode Island, United States (N = 1197) in May-June 2017. The dependent variable was burnout, measured with the validated Mini z burnout survey. The main independent variables were three EHR-related stress measures: time spent on the EHR at home, daily frustration with the EHR, and time for documentation. Logistic regression was used to measure the association between EHR-related stress and burnout before and after adjusting for demographics, practice-level characteristics, and the other EHR-related stress measures. Of the 371 participants, 73 (19.8%) reported at least one symptom of burnout. Among participants with an EHR (N = 333), 165 (50.3%) agreed or strongly agreed that the EHR added to their daily frustration and 97 (32.8%) reported an insufficient amount of time for documentation. After adjustment, insufficient time for documentation (AOR = 3.72 (1.78-7.80)) and the EHR adding to daily frustration (AOR = 2.17 (1.02-4.65)) remained predictors of burnout. Results from the present study revealed several EHR-related environmental factors are associated with burnout among APRNs. Future studies may explore the impact of addressing these EHR-related factors to mitigate burnout among this population.


Stress and immunomodulation: the role of depression and neuroendocrine function.
Considerable evidence demonstrating a relationship between stress and immune function is accumulating, and a complex chain of biologic and psychologic processes are involved. An extensive network of central nervous system and endocrine system processes may be involved in the modulation of the immune system in response to stressors.


Sister chromatid exchange induced by chromium compounds in human lymphocytes.
The objective of this study was to study was to compare chromium (Cr), nickel-chromium (Ni-Cr), and control groups for sister chromatid exchange (SCE) in lymphocytes to obtain an understanding of the mutagenic effect of Cr(VI) in humans. Subjects totaled 91 persons from the 3 groups, including 14 Cr and 34 Ni-Cr electroplating workers and 43 control group members. Results showed that blood and urine Cr concentrations were highest among Cr workers (11.39 microg/l, 14.7 microg/g creatinine), next highest among Ni-Cr workers (5.28 microg/l, 6.2 microg/g creatinine), and lowest among the control group (2.36 microg/l, NA). After adjustment for smoking habits, SCE/cell values were 10.6, 9.4, and 8.3 for Cr workers, Ni-Cr workers, and controls, respectively. A synergetic effect was shown on HFC (high-frequency cells) percentages for Cr workers who also smoked. Odds ratios were 31.78 and 3.66 that Cr and Ni-Cr workers would have higher HFC percentages than the control group, respectively. The authors conclude that SCE in lymphocytes is useful for evaluation of the biological effects of environmental mutagens.


Serum tryptophan ratio and suicidal behavior in adolescents: a prospective study.
A lower ratio of tryptophan to other amino acids in serum (tryptophan ratio), established as an index of serotonin precursor available to the brain, has been shown to be associated with increased suicidal behavior in cross-sectional studies. The purpose of this study was to conduct the first prospective examination of the utility of the tryptophan ratio along with clinical variables in predicting suicidal behavior in high-risk and reference adolescents. Adolescents with alcohol use disorders (AUDs) and prior suicidal attempts (n=20), adolescents with AUDs without suicide attempts (n=20), and community controls with neither of these characteristics (n=20) were matched on demographic variables. These groups were not significantly different on the tryptophan ratio at baseline. Of 56 subjects who completed follow-up assessments, six had suicidal behavior in the follow-up period. The tryptophan ratio, along with demographic and clinical variables, was examined using Cox regression with a backward stepwise variable elimination procedure. In the final model, the tryptophan ratio and major depressive disorder both significantly contributed to the prediction of suicidal behavior. This finding suggests that the tryptophan ratio may improve the identification of adolescents at high risk for suicidal behavior.


Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier.
The Decipher test measures expression of 22 RNA biomarkers associated with aggressive prostate cancer used to improve risk stratification of patients to help guide management. To date, Decipher's genomic classification has not been extensively correlated with specific histologic growth patterns in prostatic adenocarcinoma. With a growing understanding of the clinical aggressiveness associated with cribriform growth pattern (CF), intraductal carcinoma (IDC), and percent Gleason pattern 4 (G4%), we sought to determine if their presence was associated with an increased genomic risk as measured by the Decipher assay. Clinical use of the Decipher assay was performed on the highest Gleason score (GS) tumor nodule of prostatectomy specimens from a prospective cohort of 48 patients, with GS varying from 7 through 9 to help guide clinical risk stratification. The tumors were reviewed for CF, IDC, and G4%, which were then compared to the Decipher score (0-1) and risk stratification (high vs not high). The presence of CF/IDC was significantly associated with Decipher risk score (P = .007), with a high-risk Decipher score in 22% vs 56% of patients without or with CF/IDC. On binary logistic regression analysis, G4% (odds ratio [OR] 1.04 per percent increase [95% confidence interval [CI], 1.02-1.06]; P = .0004) and CF predominant (OR, 9.60 [95%CI, 1.48-62.16]; P = .02) were significantly associated with a high-risk GC score. IDC did not reach significance (OR, 1.92 [95%CI, 0.65-5.67]; P = .24). Our findings add to an expanding knowledge base that supports G4% and CF/IDC as molecularly unique and clinically relevant features in prostatic adenocarcinoma. These histologic features should be standardly reported as they are associated with more aggressive prostate cancer. Future work should determine the independent information of these histologic findings that are relative to genomic assessment on long-term outcomes.


A case of venous stasis colitis possibly caused by eplerenone.
A 50-year-old man was referred to our hospital for colitis with abdominal pain and diarrhea that had persisted for more than 8 months. 9 months earlier, he had been treated for fulminant eosinophilic myocarditis. During steroid therapy, ulceration appeared in the esophagus, stomach and large intestine. The biopsy results showed cytomegalovirus (CMV) inclusion bodies, and the patient was diagnosed with CMV gastrocolitis and treated with ganciclovir. Colonoscopy 7 months earlier revealed ischemia-like segmental colitis 10 cm in length in the hepatic flexure without evidence of CMV infection. Colonoscopy after 1 month and 3 months showed no improvement. We suspected drug-induced focal ischemic colitis, and discontinued eplerenone. Colonoscopy 2 months after withdrawal of eplerenone showed improvement in colitis, and colonoscopy 8 months later showed ulcer healing. Venous disorders are cautioned as a known side effect of eplerenone, but this is the first report of venous stasis colitis thought to be caused by eplerenone.


Pancreatic endocrine tumours: evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p.
Two molecular pathways leading to cancer are known. Common-type cancers arise from the 'tumour suppressor' pathway, characterized by gross chromosomal changes and allelic losses (LOH) in an average of 25 per cent or more of randomly chosen chromosomal loci. The 'mutator pathway' has been recognized in a subset of cancers, characterized by widespread microsatellite DNA instability and rarity of chromosomal losses. The present study has investigated 20 pancreatic endocrine tumours (PETs) for loss of heterozygosity (LOH) at seven chromosomal loci (3p14, 7q31-32, 11q13, 13q14, 18q21, 17p13, and 17q21); microsatellite instability; and Ki-ras, N-ras, and p53 gene mutations. LOH was found in an average of 24 per cent of the chromosomal loci analysed. No tumour showed microsatellite instability. Ki-ras and p53 mutations were each found in one case. The frequency of losses was higher in malignant (40 per cent) than in benign (17 per cent) tumours (p = 0.009), and the specific chromosome 17p13 LOH was associated with extrapancreatic extension of disease (p = 0.007), high proliferative activity (p = 0.001), and absence of progesterone receptors (p = 0.01). A common deleted region on chromosome 17p13 and the rarity of p53 gene mutations suggest the existence of a novel tumour suppressor gene involved in the pathogenesis of PETs in this chromosomal area.


[Determination of the required volume of a sampling population in scientific and practical research].
Three stages in the determination of the sampling population volume are described. The significance of a correct definition of the confidence interval is stressed, as well as the adjustment of the calculated values of the sampling population volume during the investigation.


What is appropriate target delineation for MRI-based brachytherapy for medically inoperable endometrial cancer?
For medically inoperable endometrial cancer (MIEC), the volumetric target of image-guided brachytherapy (IGBT) techniques is not well established. We propose a high-risk CTV (HRCTV) concept and report associated rates of local control and toxicity. For all MIEC patients receiving definitive external beam radiotherapy (EBRT) followed by MRI-based IGBT at a single institution, BT dose was prescribed to HRCTV defined as GTV plus endometrial cavity with a planning goal of a summed EQD2 D90 of ≥85 Gy. Freedom from local progression (FFLP) and overall survival (OS) were estimated via Kaplan Meier method. Thirty two MIEC patients received EBRT followed by MRI-based IGBT between December 2015 and August 2020. Median follow up was 19.8 months. A total of 75% of patients had FIGO stage I/II disease, 56% endometrioid histology, and 50% grade 3 disease. OS was 73.6% (95% CI 57.8%-89.3%) at 12 months and 65.8% (95% CI 48.4%-83.2%) at 24 months. FFLP was 93.8% (95% CI 85.3%-100%) at 12 months and 88.8% (95% CI 86.6%-91.0%) at 24 months. 23 (72%) patients experienced no RT-related toxicity, while 2 of 32 patients (6%) experienced late grade 3+ toxicities (grade 3 refractory vomiting; grade 5 GI bleed secondary to RT-induced proctitis). Patients with MIEC receiving definitive EBRT followed by MRI-based IGBT prescribed to the MRI-defined HRCTV demonstrated favorable long-term local control with an acceptable toxicity profile.


Role of regulatory T cells in spinal cord injury.
Spinal cord injury is an intricate process involving a series of multi-temporal and multi-component pathological events, among which inflammatory response is the core. Thus, it is crucial to find a way to prevent the damaging effects of the inflammatory response. The research has found that Treg cells can suppress the activation, proliferation, and effector functions of many parenchymal cells by multiple mechanisms. This review discusses how Treg cells regulate the inflammatory cells to promote spinal cord recovery. These parenchymal cells include macrophages/microglia, oligodendrocytes, astrocytes, and others. In addition, we discuss the adverse role of Treg cells, the status of treatment, and the prospects of cell-based therapies after spinal cord injury. In conclusion, this review provides an overview of the regulatory role of Treg cells in spinal cord injury. We hope to offer new insights into the treatment of spinal cord injury.


The tight junction protein complex undergoes rapid and continuous molecular remodeling at steady state.
The tight junction defines epithelial organization. Structurally, the tight junction is comprised of transmembrane and membrane-associated proteins that are thought to assemble into stable complexes to determine function. In this study, we measure tight junction protein dynamics in live confluent Madin-Darby canine kidney monolayers using fluorescence recovery after photobleaching and related methods. Mathematical modeling shows that the majority of claudin-1 (76 +/- 5%) is stably localized at the tight junction. In contrast, the majority of occludin (71 +/- 3%) diffuses rapidly within the tight junction with a diffusion constant of 0.011 microm(2)s(-1). Zonula occludens-1 molecules are also highly dynamic in this region, but, rather than diffusing within the plane of the membrane, 69 +/- 5% exchange between membrane and intracellular pools in an energy-dependent manner. These data demonstrate that the tight junction undergoes constant remodeling and suggest that this dynamic behavior may contribute to tight junction assembly and regulation.


International migration, sex ratios, and the socioeconomic outcomes of nonmigrant Mexican women.
This article assesses whether international migration from Mexico affects the marital, fertility, schooling, and employment outcomes of the Mexican women who remain behind by exploiting variation over time as well as across Mexican states in the demographic imbalance between men and women. I construct a gauge of the relative supply of men for women of different age groups based on state-level male and female population counts and the empirically observed propensity of men of specific ages to marry women of specific ages. Using Mexican census data from 1960 through 2000, I estimate a series of models in which the dependent variable is the intercensus change in an average outcome for Mexican women measured by state and for specific age groups, and the key explanatory variable is the change in the relative supply of men to women in that state/age group. I find that the declining relative supply of males positively and significantly affects the proportion of women who have never been married as well as the proportion of women who have never had a child. In addition, states experiencing the largest declines in the relative supply of men also experience relatively large increases in female educational attainment and female employment rates. However, I find little evidence that women who do marry match to men who are younger or less educated than themselves.


Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).
Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only. We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12). Expression levels of individual mRNAs and soluble serum biomarkers were compared by non-parametric Mann-Whitney test. The analysis also included Spearman rank correlation tests and multiple regression analysis. For co-correlated genes, the factor analysis was performed. The total serum levels of apoptotic biomarker M30 were significantly elevated in PCOS patients with liver steatosis as compared to non-PCOS NAFLD controls (P < 0.02), pointing that androgen-dependent proapoptotic PCOS environment that may directly contribute to NAFLD progression in these patients. Similarly, hyperandrogenism may explain the observed PCOS-specific decrease (P < 0.04) in adipose LDLR mRNA expression that may be connected to the proneness of PCOS patients to NAFLD. The levels of mRNA encoding angiogenesis-associated GSK-3B interacting protein ninein were also significantly increased in the adipose tissue of NAFLD patients with PCOS (P < 0.007). Furthermore, the levels of resistin positively correlated with expression levels of LDLR and prothrombin time (PT). An androgen-dependent proapoptotic PCOS environment may directly contribute to NAFLD progression in these patients. Hyperandrogenism may explain an observed decrease in adipose LDLR mRNA expression. An inflammation-associated increase in the release of resistin into circulation might contribute to the prothrombotic state observed under conditions associated with insulin resistance, including PCOS. The studies of larger cohorts of NAFLD with and without PCOS patients are needed to further assess these potential interactions.


Short-term effects of sibutramine on mineral status and selected biochemical parameters in obese women.
The aim of this study was to assess the effect of sibutramine on mineral status and selected biochemical parameters in obese women. The study was conducted on 24 patients who received 15 mg daily doses of sibutramine for 12 weeks, and on 20 patients who received placebo. At the baseline, after the sixth and twelfth weeks of treatment, body weight and blood pressure were measured, the BMI was calculated, and samples of blood and of first morning urine were collected. Serum lipid profiles, glucose levels, and nitric oxide levels were determined. The iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), and magnesium (Mg) present in the serum and urine samples were assessed. The erythrocyte hemolysate of the patients was use to assay the activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). No changes were observed in BMI, blood pressure, or nitric oxide during the study. After 12 weeks of treatment, a decrease was observed in total cholesterol, LDL cholesterol, triglyceride, glucose, and ferritin levels. GSH-Px and SOD activity increased after 12 weeks of sibutramine treatment. The Mg and Cu increases was observed in serum after the sixth and twelfth weeks of treatment. It was found that the Zn level decreased in serum after the twelfth week. The elimination of Ca, Mg, Fe, Zn, and Cu in urine also declined in the twelfth week. No differences were found in the women taking the placebo. In conclusion, we found that sibutramine had a positive effect on lipid and glucose status in obese women. However, the drug disturbed the balance of minerals, especially Zn and Mg, in the subjects.


Potential for increasing conspicuity of short-T1 lesions in the brain using magnetisation transfer imaging.
We investigated the feasibility of using T1-weighted magnetisation transfer sequences to generate tissue contrast and increase the conspicuity of short-T1 areas within the brain. We imaged two normal volunteers with and without saturating off-resonance radiofrequency irradiation at a range of repetition times (TR 200-760 ms). T1 values and magnetisation transfer ratios for white matter and deep grey matter were calculated. We studied eight patients with intracranial lesions showing short-T1 areas, using mildly T1-weighted sequences with and without magnetisation transfer contrast. Lesion numbers, areas and signal intensities were measured and lesion-to-background contrast was calculated. Comparison was made with conventional T1-weighted spin-echo images. In the normal volunteers, contrast between the thalamus, caudate and lentiform nuclei and white matter showed striking visual differences, with magnetisation transfer weighing, with decreasing TR. In all patients, short-T1 lesions were seen more clearly on magnetisation transfer-weighted images, with significant increase in lesion number, area and contrast, when compared with conventional T1-weighted scans.


Hydatid cyst of the rib with intramedullary involvement.
Osseous localization is uncommon for a hydatid cyst. We present a case of a hydatid cyst with rib involvement spreading through the bone marrow in a 62-year old woman.


Spermine stimulates the threonyl-tRNA formation in rat liver.
The effects of spermine have been studied on the aminoacylation reaction catalyzed by rat liver threonyl-tRNA synthetase. Spermine can not replace Mg2+ in this reaction. However, a stimulatory and synergistic effect was observed on the threonyl-tRNA formation, in the presence of spermine and suboptimal concentration of Mg2+. Other divalent cations like Ba2+, Ca2+, Mn2+ and Co2+ can substitute Mg2+ in the threonyl-tRNA formation, but in all these cases spermine had no significant effect. Spermine prevented the inhibitory effects caused by excess of ATP or tRNA on the aminoacylation reaction. Association constants were determined by equilibrium dialysis for the tRNA-spermine complex (Ka = 3.7 x 10(3) M-1) and by differential spectrophotometry for the ATP-spermine complex (Ka = 7.8 x 10(3) M-1). No enzyme-spermine complex could be detected by equilibrium dialysis. Some roles have been ascribed for the polyamine spermine in the stimulation of the threonyl-tRNA formation. ATP-spermine and tRNA-spermine can not function as substrates for the threonyl-tRNA synthetase, since Mg2+ is indispensable. The stimulatory effect by spermine is important considering the physiological concentration of Mg2+ in the tissues. Probably in vivo spermine would have a relevant role lowering the real Mg2+ concentration required in the aminoacylation reaction.


Perceptions of breast health awareness in Black British women.
Breast cancer is a global concern. Published studies indicate that 43% of Black and ethnic minority women interviewed have reported that they did not practice breast awareness because they did not know the relevant breast changes that occur in breast cancer. Black women are also more likely to receive a diagnosis of breast cancer when it is in an advanced stage. This pilot study aimed to address the views of Black British women on breast health awareness and breast health screening practices. In this qualitative study I used semi-structured interviews were used to investigate breast health perceptions, practices and education in a pilot sample of ten women. Women held numerous perceptions of breast cancer which ranged from no knowledge to well informed through receiving extensive education. Two out of ten women were relatively uneducated with regard to breast self examination (BSE). The remaining eight women participated in a variety of screening routines which varied from undertaking BSE everyday to once every few months. Women's experience of breast health education was also variable. One woman, younger woman, had not received any health education advice in relation to breast health awareness or BSE. The remaining nine women had received some health advice following visit to their General Practitioners, Medical consultant, media information or as a result of participating in mammographic screening. Black British women require health education that focuses on breast cancer and its associated risk factors, technique of BSE, and national breast cancer screening recommendations.


Assessing the accuracy of colposcopy at predicting the outcome of abnormal cytology in pregnancy.
To determine the accuracy of colposcopic and cytological assessment at predicting final histological diagnosis in women referred with abnormal cervical smears during pregnancy; to use this data as a basis for a follow up protocol for pregnant patients referred with abnormal cervical cytology. Retrospective analysis of women referred to Queens Medical Centre, Nottingham, UK with abnormal cytology whilst pregnant between 1994 and 2003. Forty-nine patients in total were included in the study. Colposcopic assessment in the antenatal period had a concordance with final histological diagnosis in 60% of patients and a concordance of 68% when undertaken in the post-natal period. Cytological concordance was lower at 58%. In only six percent of patients was a cervical biopsy undertaken and there were no complications as a result. There was a fall in colposcopically assessed high-grade cervical intraepithelial neoplasia between the antenatal and post-natal period. No cases of invasive cancers were diagnosed antenatally. A policy of conservative management of pregnant patients during the antenatal period is supported by this data. A suggested protocol of one colposcopic assessment at the time of the index abnormal smear followed by a post-partum colposcopy, and appropriate treatment is suggested.


Systematic mapping review of orthognathic surgery.
Systematic mapping review AIM AND SCOPE: The objective of this mapping review was to identify, describe, and organize clinical research currently available from systematic reviews and primary studies regarding co-interventions and different surgical modalities used in orthognathic surgery (OS) and their outcomes. Systematic reviews (SRs), randomized controlled trials, and observational studies that evaluated perioperative OS co-interventions and surgical modalities were identified in an exhaustive search of MEDLINE, EMBASE, Epistemonikos, Lilacs, Web of Science, and CENTRAL. Grey literature was also screened. Included were 35 SRs and 253 primary studies, 103 from SRs, and another 150 identified in our search. Overall, SR quality was rated as critically low, with only two SRs rated as of high quality. 19 questions on population, interventions, comparisons, and outcomes (PICO) extracted from the SRs focused on osteosynthesis methods, surgical cutting devices, and use of antibiotics, corticosteroids, and induced hypotension. Also identified were 15 research gaps. Evidence bubble maps were created to graphically depict the available evidence. Future high-quality research, both primary and secondary, is needed to address the knowledge gaps identified in this systematic mapping review.


Diffraction gratings of photosensitive ZrO2 gel films fabricated with the two-ultraviolet-beam interference method.
Photosensitive ZrO(2) gel films were patterned with a two-beam interference method by use of a 325-nm-wavelength He-Cd laser for the first time to our knowledge. The ZrO(2) gel films were prepared from Zr(O-n-C(4)H(9))(4) chemically modified with benzoylacetone. We fabricated uniform gratings with a 0.5-microm period on Si or SiO(2) substrates by etching the gel films in ethyl alcohol after UV irradiation. A maximum diffraction efficiency of 28% was attained with the grating fabricated on Si substrate under a Littrow mounting condition by use of a 633-nm-wavelength He-Ne laser. Blazed gratings could also be fabricated.


Validation of the Ottawa knee rules in an emergency teaching centre.
Our objective was to determine the value of the Ottawa knee rules when applied by users with different levels of clinical training. We used a prospective patient survey by the medical students and surgery residents of a European university trauma centre. The study group consisted of 261 eligible patients who presented with acute knee trauma during a 6-month period. Radiography or follow-up was obtained for each patient. Data were separately analysed according to the degree of qualification of the initial examiner. The Ottawa knee rules had a sensitivity and a negative predictive value of 1.00. Variable degree of medical competence of the users did not alter the accuracy of the rules. Application of the rules would have reduced knee radiography requests by 25%. The Ottawa knee rules remain highly sensitive when applied by medical users with different levels of qualification, such as encountered in a teaching setting.


Non-invasive assessment of liver fibrosis in a rat model: shear wave elasticity imaging versus real-time elastography.
The purpose of this study was to investigate the diagnostic value of shear wave elasticity imaging (SWEI) and real-time elastography (RTE) in liver fibrosis induced by dimethylnitrosamine (DMN) and to compare the accuracy of these methods. Seventy male Wistar rats given a single intra-peritoneal injection of DMN and 10 control rats given a saline injection underwent SWEI and RTE to determine their shear wave velocity (V(s)) and liver fibrosis (LF) index, respectively. Correlations between V(s) or the LF index and histologic stage of liver fibrosis (S0-S4) were analyzed, and the diagnostic values of the techniques were assessed using a receiver operating characteristic curve. A positive correlation was found between V(s) and stage of liver fibrosis (r = 0.947, p < 0.001) and between LF index and stage (S) of liver fibrosis (r = 0.662, p < 0.001). For Vs, the areas under the receiver operating characteristic curve for the diagnosis of fibrosis, S ≥ S1, S ≥ S2, S ≥ S3 and S = S4, were 0.983, 0.995, 0.999 and 0.964, respectively; for the LF index, the values were 0.871, 0.887, 0.761 and 0.839, respectively (all p < 0.001). Vs and the LF index values in rats with severe inflammatory activity were significantly higher than those in controls (p < 0.001). In conclusion, positive correlations exist between V(s) or the LF index and the severity of liver fibrosis in rats. Vs is more accurate than the LF index in predicting liver fibrosis in rats. However, severe inflammatory activity may reduce the accuracy of both techniques.


Dye removal by almond shell residues: studies on biosorption performance and process design.
The objective of this research paper is to assess the biosorption potential of almond shell residues for methyl orange dye. The pseudo-second-order kinetic model described the dye biosorption process with a good fitting. The relationship between the pseudo-second-order model constants and the biosorption performance was also evaluated. The equilibrium data fit well with the Langmuir isotherm model presenting that the biosorption was the monolayer coverage of dye on the biosorbent and the homogeneity of active sites for dye binding on the biosorbent surface. Based on the Langmuir model, a single-stage batch biosorber was also designed to predict the biosorbent mass for certain percentage dye removal. Besides, the standard Gibbs free energy change was also calculated to define the nature of biosorption process. These results revealed that the utilization of almond shell residues as dye biosorbent could be an interesting option from both environmental and economic point of view.


Cardiovascular evaluation of obligate heterozygotes in Friedreich's ataxia.
A study of 17 parents (obligate heterozygotes) of children with Friedreich's ataxia was carried out. In addition to medical histories and physical examinations, a standard 12 lead ECG tracing was obtained. In the age group below 50, there was no significant evidence of ischaemic or primary cardiomyopathy. Older subjects had more frequent risk factors for arteriosclerotic heart disease.


Depression in lung cancer patients: the role of perceived stigma.
Previous research has shown that lung cancer patients are at an increased risk for depressive symptomatology; however, little is known about the factors contributing to depression in these patients. This study focused on the possible association between perceived stigma related to a lung cancer diagnosis and depressive symptomatology. It was hypothesized that greater perceived stigma would be related to greater depressive symptomatology and that perceived stigma would account for variance in depressive symptomatology above and beyond that accounted for by relevant clinical, demographic, and psychosocial variables. A sample of 95 participants receiving chemotherapy for stage II-IV non-small cell lung cancer was recruited during routine outpatient chemotherapy visits. Participants completed a demographic questionnaire and self-report measures assessing perceived stigma, depressive symptomatology, and other psychosocial variables. A medical chart review was conducted to assess clinical factors. As hypothesized, there was a positive association between perceived stigma and depressive symptomatology, r = 0.46, p<0.001. Perceived stigma also accounted for significant unique variance in depressive symptomatology above and beyond that accounted for by relevant demographic, clinical, and psychosocial factors, β = 0.19, p<0.05. Future research should aim to replicate and extend these findings in longitudinal studies and explore whether lung cancer patients' depressive symptomatology can be ameliorated by targeting perceived stigma.


Transcription analysis of pyranose dehydrogenase from the basidiomycete Agaricus bisporus and characterization of the recombinantly expressed enzyme.
Agaricus bisporus is a litter degrading basidiomycete commonly found in humic-rich environments. It is used as model organism and cultivated in large scale for food industry. Due to its ecological niche it produces a variety of enzymes for detoxification and degradation of humified plant litter. One of these, pyranose dehydrogenase, is thought to play a role in detoxification and lignocellulose degradation. It is a member of the glucose-methanol-choline family of flavin-dependent enzymes and oxidizes a wide range of sugars with concomitant reduction of electron acceptors like quinones. In this work, transcription of pdh in A. bisporus was investigated with real-time PCR revealing influence of the carbon source on pdh expression levels. The gene was isolated and heterologously expressed in Pichia pastoris. Characterization of the recombinant enzyme showed a higher affinity towards disaccharides compared to other tested pyranose dehydrogenases from related Agariceae. Homology modeling and sequence alignments indicated that two loops of high sequence variability at substrate access site could play an important role in modulating these substrate specificities.


Modulatory roles of GABAergic mechanisms in post-rotatory nystagmus in the rabbit.
1. To determine how the GABAergic mechanism operates in the generation of post-rotatory nystagmus, an experiment was performed with GABAergic drugs in rabbits. 2. Subconvulsive doses of picrotoxin (0.3-0.6 mg/kg, i.v.) and bicuculline (0.1 mg/kg, i.v.) decreased the number of post-rotatory nystagmus beats, whereas strychnine sulphate, at a subconvulsive dose (0.1 mg/kg i.v.), increased it. 3. Diazepam (1 mg/kg, i.v.) remarkably increased the number of post-rotatory nystagmus beats. Pretreatment with picrotoxin (0.45 mg/kg, i.v.), bicuculline (0.1 mg/kg, i.v.) or semicarbazide-HCl (180 mg/kg, i.v.) antagonized the effects of diazepam (1 mg/kg, i.v.). 4. GABAergic mechanisms may play a modulatory role in the production of nystagmus rhythm. Strychnine-sensitive neurons involved in the vestibular mechanism may behave in a different manner from picrotoxin-sensitive neurons.


Effects of Jiuqu inoculating Rhizopus oryzae Q303 and Saccharomyces cerevisiae on chemical components and microbiota during black glutinous rice wine fermentation.
In this study, the physicochemical properties, metabolites, sensory characteristics, and microbiota of black glutinous rice wine (BGRW) during traditional fermentation (TF) and inoculated fermentation (IF) were investigated, and their correlation relationships were revealed. Results indicated that IF promoted total sugar utilization and ethanol and esters synthesis in BGRW. Altogether 67 reliable metabolites were identified, 36 of which were labeled components, primarily esters (OAV > 1). Meanwhile, the concentrations of ethanol, esters, and total flavor on the 11th day of IF were close to those on the 22nd day of TF. Combined with the sensory description indicated that the IF could improve the quality of BGRW. Besides, TF contains vast unfavorable microorganisms, such as Chaetomium, Penicillium, Stachybotrys, and Trichocladium. Therefore, IF can accelerate the fermentation and enhance the flavor of BGRW, and inhibit the growth of pathogenic and spoilage organisms. Finally, Pearson's correlation analysis demonstrated that Saccharomyces, Rhizopus, Lactobacillus, Aspergillus, and Bacillus were the pivotal functional microorganisms in BGRW. The study provided scientific and effective basis for improving the quality, shortening the fermentation cycle, and controlling pathogenic and spoilage organisms of BGRW.


Short-course antibiotic therapy for hospitalized patients with early clinical response in community-acquired pneumonia: a multicentre cohort study.
To explore whether short-course antibiotic therapy is efficient and safe in routine clinical settings among patients hospitalized with community-acquired pneumonia (CAP) who achieve an early clinical response. During 2017-2019, we conducted a cohort study of patients admitted with CAP to four hospitals in Denmark. Data were prospectively gathered from medical records and enriched with data from nationwide registries. In the present study, we included patients with early clinical response and divided them into treatment groups based on antibiotic duration, as decided by the attending physician: short-course (4-7 days) or prolonged-course (8-14 days). The primary outcome was post-treatment mortality within 30 days. Secondary outcomes included readmissions or new antibiotics. Logistic regression models were used to estimate ORs with 95% CIs, and inverse probability weighting was applied to adjust for confounding. The study cohort included 1151 patients with a median age of 74 years, predominantly presenting with mild-moderate disease. The 30-day post-treatment mortality was 3.36% (11/327) in the short-course group and 3.40% (28/824) in the prolonged-course group (adjusted OR 1.05, 95% CI 0.38-1.88). Readmission occurred in 15.6% (42/269) vs. 14.0% (102/727) (adjusted OR 1.07, 95% CI 0.75-1.69) and new prescription of antibiotics in 11.9% (32/269) vs. 12.1% (88/727) (adjusted OR 0.99, 95% CI 0.61-1.49). In patients hospitalized with CAP and early clinical response, similar outcomes were observed between short-course and prolonged-course therapies. These results support the use of short-course therapy in routine clinical settings.


Pattern segmentation in a binary/analog world: unsupervised learning versus memory storing.
We discuss the problem of segmentation in pattern recognition. We adopt the model and the general approach in the landmark paper by Wang, Buhmann and von der Malsburg (Neural Computation, (1990), 2, 94-106), and expand their model in a number of ways. We review their solution to the segmentation problem in associative memory, which consists in feature binding being expressed by synchrony relations between oscillators or populations of neurons. We extend the model by introducing a law of synaptic change, which allows the network to learn by structuring itself in response to stimuli with relevant features. We discuss the problem of interference between pattern completion and the learning of new memories. We also propose a form of multiplexing of input information taking advantage of the time-structure of the neurons' response. It is based on the assessment of analog as well as of binary properties of the stimuli and provides for an enhancement of the network's processing capacity. The relevance of the results for biological systems is pointed out.


Release of noradrenaline by the ionophore X537A from normal and reserpinized guinea-pig atrium.
The effects of ionophore X537A on the release of 3H-noradrenaline and its metabolites from the superfused guinea-pig left atrium were investigated. Concentrations of ionophore of 10 and 30 mocrometer greatly increased the release of tritium. Of the total increase in radioactivity elicited by X537A 44% was accounted for as noradrenaline and 50% was due to deaminated metabolites. The ionophore-evoked release of tritium was independent of the extracellular calcium ions and was not affected by agents which modify calcium movements such as verapamil, ryanodine, ruthenium red and tetracaine. X537A released 3H-noradrenaline from extragranular sites in MAO-inhibited atria from reserpine-treated animals and this release was also calcium independent. It is concluded that the ability of X537A to release noradrenaline from vesicular or cytoplasmic sites is not related to its ability to couple with and transport calcium ions through membranes. The ionophore might modify the ionic distribution outside and inside the neuronal membrane which would lead to leakage of the transmitter.


Superenhancer-transcription factor regulatory network in malignant tumors.
This study aims to identify superenhancer (SE)-transcriptional factor (TF) regulatory network related to eight common malignant tumors based on ChIP-seq data modified by histone H3K27ac in the enhancer region of the SRA database. H3K27ac ChIP-seq data of eight common malignant tumor samples were downloaded from the SRA database and subjected to comparison with the human reference genome hg19. TFs regulated by SEs were screened with HOMER software. Core regulatory circuitry (CRC) in malignant tumor samples was defined through CRCmapper software and validated by RNA-seq data in TCGA. The findings were substantiated in bladder cancer cell experiments. Different malignant tumors could be distinguished through the H3K27ac signal. After SE identification in eight common malignant tumor samples, 35 SE-regulated genes were defined as malignant tumor-specific. SE-regulated specific TFs effectively distinguished the types of malignant tumors. Finally, we obtained 60 CRC TFs, and SMAD3 exhibited a strong H3K27ac signal in eight common malignant tumor samples. In vitro experimental data verified the presence of a SE-TF regulatory network in bladder cancer, and SE-TF regulatory network enhanced the malignant phenotype of bladder cancer cells. The SE-TF regulatory network with SMAD3 as the core TF may participate in the carcinogenesis of malignant tumors.


MR imaging of pelvic floor relaxation.
The wide variety of available surface coils, pulse sequences, and post-processing techniques make MR imaging a useful clinical and research tool for evaluation of pelvic floor relaxation. Cases of isolated cystocele do not require imaging; however, in cases in which multiple compartments of the pelvis are involved or the patient has failed prior surgery, MR imaging should be considered for preoperative planning.


Informed consent documents do not encourage good-quality decision making.
Informed consent for research has emphasized information provision over support to people making a difficult decision. We assessed the extent to which existing informed consent documents (ICDs) conform to the International Patient Decision Aid Standards for supporting decision making. One hundred thirty-nine ICDs for trials registered with ClinicalTrials.gov were obtained from study investigators. Using a four-point scale, two raters assessed each ICD on 32 items. Overall agreement between raters was 95.1% (linear weighted kappa-0.745). For 12 items focused on providing enough information, conformity was above 50% for three, and 0% for another four. For all eight items focused on how to present outcome probabilities, conformity was below 20%. For two items focused on clarifying and expressing values, conformity was below 10%. For two items focused on improving structured guidance, conformity was below 5%. For four items focused on using evidence, one item showed conformity of 74%; all others showed conformity below 5%. For four items focused on transparency, conformity was high (above 60% for two, above 80% for the others). Existing ICDs do not meet most validated standards for encouraging good decision making. These standards make clear predictions about how one might improve ICDs ensure that research participants are fully informed.


Second-order mappings in grapheme-color synesthesia.
Typically, the search for order in grapheme-color synesthesia has been conducted by looking at the frequency of certain letter-color associations. Here, we report stronger associations when second-order similarity mappings are examined--specifically, mappings between the synesthetic colors of letters and letter shape, frequency, and position in the alphabet. The analyses demonstrate that these relations are independent of one other. More strikingly, our analyses show that each of the letter-color mappings is restricted to one dimension of color, with letter shape and ordinality linked to hue, and letter frequency linked to luminance. These results imply that synesthetic associations are acquired as the alphabet is learned, with associations involving letter shape, ordinality, and frequency being made independently and idiosyncratically. Because these mappings of similarity structure between domains (letters and colors) are similar to those found in numerous other cognitive and perceptual domains, they imply that synesthetic associations operate on principles common to many aspects of human cognition.


One-Stage Revision for Infected Total Hip Arthroplasty.
Prosthetic joint infection (PJI) is a challenging complication following total hip arthroplasty (THA). Two-stage exchange arthroplasty is preferred for treating chronic PJI of THA, although specialized centers have reported comparable outcomes with protocol-based, 1-stage exchange arthroplasty. A main requirement is presurgical determination of the infecting organism's sensitivity. The therapeutic goal is control of the infection and maintenance of joint function. It offers advantages, including a single operative procedure, fewer antibiotics, and reduced hospitalization time and relative overall costs.


Can we predict failure of percutaneous fixation of femoral neck fractures?
This study evaluated a series of geriatric femoral neck fracture treated with closed reduction percutaneous pinning (CRPP) at a single level-1 trauma center to determine if there are any simple, reliable, radiographic characteristics that can be used to predict increased risk of post-operative failure in nondisplaced and valgus impacted fracture patterns. We conducted a retrospective cohort study of all patients with femoral neck fractures (AO/OTA 31B) who underwent CRPP over a 12-year period at a single Level 1 trauma center. Failure was defined as radiographic failure within the first year after the index operation requiring revision surgery. Common patterns identified on initial review were the presence of a visible medial transcervical line (MTL) felt to indicate a tension-sided failure, a straight inferior calcar (SIC) indicating severe valgus impaction, and quality of intra-operative screw positioning. X-rays of patients were then reviewed for these characteristics in a blinded manner by three different trauma-fellowship trained orthopedic surgeons. Inter-rater reliability was calculated using Fleiss' Kappa Coefficient. Comparisons of failure rates between groups were made using a Fisher's Exact test. 139 patients who underwent CRPP for a femoral neck fracture and follow-up for at least 90 days were identified and reviewed. There were a total of 19 failures (13.6%) within one year. The patients with a varus fracture had a failure rate of 9/24 (37.5%). Of the valgus/nondisplaced fractures, MTL was identified in 42/115 (36%) patients. Inter-rater agreement was high for the presence of an MTL (84%, Kappa 0.69). Patients with an MTL had a fourfold increase in risk of failure (7/42=17% with an MTL vs. 3/73=4% without, p 0.03). The presence of a SIC and quality of screw placement were not predictive of failure. Varus femoral neck fractures fixed with CRPP have a high rate of failure (37.5%). Nondisplaced or valgus impacted fractures with the presence of a visible medial transcervical line on pre-operative radiographic imaging resulted in a fourfold increase in the risk of failure after CRPP. Identification of the MTL will help treating surgeons better council patients when making pre-operative decisions between arthroplasty and CRPP.


Standard diagnostic programmed electrical stimulation protocols in patients with paroxysmal recurrent tachycardias.
Programmed stimulation, as a diagnostic and therapeutic modality in arrhythmia evaluation, suffers from lack of standardization. If the sensitivity, specificity, and predictive value of this procedure are to be considered seriously, then an evaluation of various stimulation protocols is warranted. Study variables are numerous and influence the outcome of the studies.


Long-term effect of tumor necrosis factor and gamma interferon in human pancreatic carcinoma cells.
The long-term cytotoxic/cytostatic effects of recombinant human tumor necrosis factor alpha (rhTNF) and gamma interferon (rhIFN-gamma) were studied in five human pancreatic carcinoma cell lines. The pancreatic tumor cell lines were heterogenous in their response to individual cytokines. During a 7-d incubation, MIA PaCa-2 cells were more sensitive to rhTNF than rhIFN-gamma, whereas ASPC-1, T3M4, and COLO 357 cells were more sensitive to rhIFN-gamma than rhTNF. PANC-1 cells were relatively insensitive to both cytokines. In a previous report, we demonstrated synergistic cytotoxic effects of rhTNF and rhIFN-gamma during 48-h incubations in ASPC-1 and COLO 357 cells (Raitano et al, Pancreas, April, 1990). In this study, a 7-d treatment with both rhTNF and rhIFN-gamma did not produce synergistic effects in any of the cell lines. However, a 24-h treatment with rhIFN-gamma, followed by removal of the cytokine, markedly increased the long-term cytotoxic/cytostatic effects of rhTNF in ASPC-1, COLO 357, and T3M4 cells. In contrast, a similar pretreatment with rhTNF did not increase the long-term cytotoxic/cytostatic effects of rhIFN-gamma in any of the cell lines. These data suggest that, in some human pancreatic carcinoma cell lines, rhIFN-gamma may be especially useful in the long-term suppression of growth. Furthermore, brief pulses of rhIFN-gamma may also be especially efficacious when followed by a subsequent prolonged exposure of cells to rhTNF.


Tissue water relations of four co-occurring chaparral shrubs.
Chaparral shrubs of California have a suite of morphological and physiological adaptations to withstand the prolonged summer droughts of a mediterranean climate. Not all species of chaparral have the same rooting depth and there is some evidence that those with shallow roots have tissue that is most tolerant to water stress. We tested this notion by comparing the tissue water relations of four co-occurring chaparral shrubs: Quercus durata, Heteromeles arbutifolia, Adenostoma fasciculatum, and Rhamnus californica. We used a pressure-volume technique and a dew-point hygrometer to metsure seasonal changes in osmotic potential when plant tissue was fully hydrated and osmotic potential at predawn, midday, and the turgor loss point. We also calculated seasonal changes in the minimum daily turgor potential, saturated weight/dry weight ratio of leaf tissue, and the bulk modulus of elasticity. We had information on the seasonal water use patterns and apparent rooting depths of these same four shrubs from a previous study (Davis and Mooney 1986). All evidence indicated that Rhamnus had shallow roots and Quercus deep roots. Our results indicated that the tissue water relations of our four co-occurring chaparral shrubs were not alike. Even though Rhamnus had shallow roots, it had the least xerophytic tissue. Seasonal osmotic potential and saturated weight/dry weight ratios were relatively high and bulk modulus of elasticity and minimum daily turgor potentials were low. Furthermore, even though Quercus had deep roots and experienced no seasonal water stress at our study site, its tissue water relations indicated relatively high tolerance to water stress. We conclude that seasonal drought tolerance of stem and leaf tissue of co-occurring chaparral shrubs does not necessarily correspond to rooting depth, to soil moisture resources available to the shrub, or to the degree of seasonal water stress experienced by the shrub.


[Skeletal scinitgraphy in neuroradiological diagnostics (author's transl)].
From a review of 52 selected cases showing neurologic symptoms, the possible use of skeletal scintigraphy for the purpose of neuroradiologic diagnostics is reported. The close relationship of the nervous system and surrounding structures with the skeletal system means that the skeletal system is often involved in nervous pathologic processes. Such involvement can be detected by skeletal scintigraphy which thus provides a vital aid to diagnosis and therapeutical planning. The basic methods and technical equipment in the field of scintigraphy are discussed.


Clinical characteristics of elderly depressive patients with low metaiodobenzylguanidine uptake.
Recently, depression with Lewy body pathology before the appearance of parkinsonism and cognitive dysfunction has been drawing attention. Low cardiac metaiodobenzylguanidine (MIBG) uptake is helpful for early differentiation of Lewy body disease (LBD) from late-onset psychiatric disorders even before parkinsonism or dementia appears. In this study, we used MIBG uptake as a tool in suspected LBD, and evaluated the relationship of MIBG results to clinical characteristics and depressive symptoms. Fifty-two elderly inpatients with depression were included in this study. The Hamilton Depression Rating Scale (HDRS) was administered at admission, and 123 I-MIBG cardiac scintigraphy was performed. Of 52 patients, 38 had normal and 14 had reduced MIBG uptake. Correlation analyses of the late phase heart-to-mediastinum (H/M) ratio on the MIBG test and each item of the HDRS revealed that the H/M ratio was significantly correlated with scores of 'agitation', 'anxiety-somatic', and 'retardation' on the HDRS. Mean HDRS composite scores of 'somatic and psychic anxiety (Marcos)' and 'somatic anxiety/somatization factor (Pancheri)' were higher in the low uptake group than in the normal uptake group. Elderly patients with depression who manifested an obvious somatic anxiety tend to show low MIBG uptake, and are more likely to have Lewy body pathology.


Indirect effect on survivorship of caterpillars due to presence of invertebrate predators.
An indirect effects is defined here as a reduction in prey survivorship as a consequence of a reduction in growth rate of prey due to the presence of a predator that alters prey behavior. A method for partitioning the direct and indirect effects of predators on prey survivorship indicated that predatory wasps (Polistes sp.:. Vespidae) had both direct and indirect negative effects on survivorship of buckmoth caterpillars (Hemileuca lucina: Saturniidae). In a field experiment, the direct and indirect effects together accounted for 61% of the mortality of the caterpillars. A third of this reduction in survivorship due to the wasps was attributed to an indirect effect, due to the decreased growth rate of the caterpillars that moved into the interior of the hostplant to escape from the wasps. In contrast, in another field experiment, although predatory stinkbugs (Podisus maculiventris: Hemiptera) contributed to 56% of the mortality of buckeye caterpillars (Junonia coenia: Nymphalidae), the indirect effect of stinkbugs on buckeye caterpillars only accounted for 2% of the reduction in survivorship of these caterpillars. These differences in the indirect effect are discussed in particular relative to the behavior of predators and prey, ratio of predator to prey sizes, and morphology of the hostplants.


A Direct, Chemo-, and Regioselective Cross-Coupling Reaction of Arenes via Sequential Directed ortho Cuprations and Oxidation.
Direct cross-coupling of Csp2-H/Csp2-H bonds of two arenes was achieved in 30-76% yield via sequential directed ortho cuprations (DoCu) with the cuprate base (TMP)2Cu(CN)Li2 (1, TMP = 2,2,6,6-tetramethylpiperidido), followed by oxidation. This methodology offers easy access to unsymmetric biaryls from arenes with a variety of directed metalation groups (DMGs) and ancillary functional groups, taking advantage of the highly chemoselective action of 1.


Loss of discordant cells during micro-mass differentiation of embryonic stem cells into the chondrocyte lineage.
Embryonic stem cells (ESCs) have attracted particular interest in regenerative medicine because of their unlimited self-renewal and multipotentiality for differentiation. Spontaneous differentiated ESCs display heterogeneous multipotent cell populations and generate teratomas in vivo, with process by which ESCs differentiate into specific lineages remaining unclear. In this study, we focused on the in vitro chondrocyte differentiation of ESCs through micro-mass without using an embryoid body (EB) step and observed the unique characteristics of cartilage formation coupled with endochondral ossification in vivo. This approach resulted in an aggressive loss of discordant cells by apoptosis, which was accompanied by significant changes in gene expression during the course of ESC differentiation into chondrocytes. Unlike EB formation where discordant cells remain trapped within aggregates, micro-mass permits cells to die, leave the group and/or form a new group in response to changes in gene expression. Our observations suggest that the cell death that accompanies ESC micro-mass differentiation helps purify a terminally differentiated cell population and selects for targeted end points within a suitable microenvironment.


Realising the potential of Natura 2000 to achieve EU conservation goals as 2020 approaches.
In the last decades the EU has made substantial efforts implementing conservation strategies to halt biodiversity loss. However, little improvement has been reported. Given the proximity of the 2020 landmark set by the EU Biodiversity Strategy and the Convention for Biological Diversity, alternatives to reduce this conservation gap and prospect future strategies must be assessed urgently. Here, we explore how the current Natura 2000 could be used to enhance management of terrestrial and freshwater threatened vertebrates. We identified Natura 2000 sites to increase the coverage of threatened species as target species under two alternative scenarios: a policy-driven approach including only threatened vertebrates listed in the Directives; and a conservation-driven approach, including all the remaining threatened vertebrates. We show that representation of threatened vertebrates in Natura 2000 could be improved by updating lists of target species in less than 1% and 3% of sites in the policy-driven and conservation-driven scenarios, respectively. We highlight the strength of Natura 2000, with sites that complement each other and could contribute to achieving more ambitious conservation targets under future strategies. Prioritisation exercises like this could help realise the potential of this network and enhance the management of threatened species and improve current gaps.


Genetic evidence and the modern human origins debate.
A continued debate in anthropology concerns the evolutionary origin of 'anatomically modern humans' (Homo sapiens sapiens). Different models have been proposed to examine the related questions of (1) where and when anatomically modern humans first appeared and (2) the genetic and evolutionary relationship between modern humans and earlier human populations. Genetic data have been increasingly used to address these questions. Genetic data on living human populations have been used to reconstruct the evolutionary history of the human species by considering how global patterns of human variation could be produced given different evolutionary scenarios. Of particular interest are gene trees that reconstruct the time and place of the most recent common ancestor of humanity for a given haplotype and the analysis of regional differences in genetic diversity. Ancient DNA has also allowed a direct assessment of genetic variation in European Neandertals. Together with the fossil record, genetic data provide insight into the origin of modern humans. The evidence points to an African origin of modern humans dating back to 200,000 years followed by later expansions of moderns out of Africa across the Old World. What is less clear is what happened when these early modern humans met preexisting 'archaic human' populations outside of Africa. At present, it is difficult to distinguish between a model of total genetic replacement and a model that includes some degree of genetic mixture.


[Clinical observation on selection of acupoints on the same nerve segment for treatment of prolapxe of lumber intervertebral disc].
To search for an effective therapy for prolapse of lumber intervertebral disc. One hundred and sixteen cases of such disease were randomly divided into a treatment group (n=66) and a control group (n=50). They were treated respectively with needling acupoints at the same nervous segment and acupoints selected routinely. The clinical therapeutic effects after 2 and 3 courses were observed. The cured and markedly effective rate of 2 courses and the cured rate of 3 courses were 90.9% and 74.2% in the treatment group, respectively, which were better than 66.0% and 32.0% in the control group (P < 0.01). The acupoint selection of the same nervous segment is an effective therapy for prolapse of lumber intervertebral disc.


Human frequency-following response: representation of pitch contours in Chinese tones.
Auditory nerve single-unit population studies have demonstrated that phase-locking plays a dominant role in the neural encoding of both the spectrum and voice pitch of speech sounds. Phase-locked neural activity underlying the scalp-recorded human frequency-following response (FFR) has also been shown to encode certain spectral features of steady-state and time-variant speech sounds as well as pitch of several complex sounds that produce time-invariant pitch percepts. By extension, it was hypothesized that the human FFR may preserve pitch-relevant information for speech sounds that elicit time-variant as well as steady-state pitch percepts. FFRs were elicited in response to the four lexical tones of Mandarin Chinese as well as to a complex auditory stimulus which was spectrally different but equivalent in fundamental frequency (f0) contour to one of the Chinese tones. Autocorrelation-based pitch extraction measures revealed that the FFR does indeed preserve pitch-relevant information for all stimuli. Phase-locked interpeak intervals closely followed f0. Spectrally different stimuli that were equivalent in F0 similarly showed robust interpeak intervals that followed f0. These FFR findings support the viability of early, population-based 'predominant interval' representations of pitch in the auditory brainstem that are based on temporal patterns of phase-locked neural activity.


Efficacy and Safety of Bepridil in Chronic Stable Angina Pectoris Refractory to Nifedipine.
The efficacy and safety of bepridil in chronic stable angina pectoris refractory to an extended-release preparation of nifedipine were evaluated in this open-label prospective study. Patients whose angina had not responded adequately to maximum tolerated doses of nifedipine received bepridil for 8 weeks after a 2-week baseline period at their established dose of nifedipine. Twenty-five patients entered the bepridil treatment period. Total exercise time (mean plus minus SD) was significantly increased at the end of bepridil therapy (9.3 plus minus 2.3 min) compared with the end of nifedipine baseline period (8.40 plus minus 2.3 min, p = 0.02). Time to the onset of angina increased from 6.1 plus minus 2.7 min to 8.1 plus minus 2.3 min, p < 0.01. Time to 1-mm ST depression increased from 7.0 plus minus 2.7 min to 8.4 plus minus 2.3 min, p < 0.01. Nitroglycerin consumption decreased from 3.01 plus minus 5.6 to 0.56 plus minus 1.3 tablets week(minus sign1), p < 0.05. The mean weekly angina attack rate decreased from 4.34 plus minus 5.3 to 1.33 plus minus 2.2, p < 0.01. Therapy with bepridil resulted in few adverse experiences. The mean QT(c) interval was significantly prolonged from 0.40 + 0.03 s at baseline to 0.45 + 0.045 s at the end of bepridil therapy (p < 0.001). There were no serious adverse events. The results of this study indicated that bepridil provides effective and safe treatment of stable angina pectoris in patients whose angina is not adequately controlled by nifedipine.


Sarcoma of follicular dendritic cells in the dorsal mediastinum.
Follicular dendritic cell sarcomas (FDCSs) are very rare and usually originate in lymph nodes. We report an exceedingly rare case with localization in the dorsal mediastinum and, for the first time, provide positron emission tomography (PET) data for this tumor. This report describes the case of a 76-year-old man with a clinically aggressive tumor in the dorsal mediastinum. Computed tomography scan revealed displacement of soft tissue and lymph nodes. PET showed that the tumor had a high proliferation rate. Investigation of the successfully removed tumor mass revealed reactivity of the tumor cells for follicular dendritic cell markers and desmosomes linking adjacent tumor cells at the ultrastructural level. Marked atypia, a high mitotic rate, and areas of coagulative necrosis were found. The tumor in our case revealed the typical features and thus was classified as FDCS. In contrast to previous reports in the literature, preoperative imaging, histology, and immunohistochemistry studies indicated at least an intermediate degree of malignancy. Nevertheless, the patient made a good postoperative recovery and remained apparently disease-free 2 years later.


The Foundations of Corporate Strategies Comment on "'Part of the Solution': Food Corporation Strategies for Regulatory Capture and Legitimacy".
The "Part of the Solution" article describes how the food industry has evolved its strategies to respond to critics and government regulation by co-option and appeasement to create a less hostile environment. Rather than focusing research on single industries it would be more efficient and productive to focus on corporate political activities (CPAs) that directly influence democratic institutions and processes having authority over laws, policy, rules and regulations that govern industry. The most influential and direct CPA are election campaign donations, lobbying, and the reverse revolving door (RRD). In the United States those CPA flow from rights of corporations that underlie all industry strategies. The US history of how corporations obtained their rights is described, and research about the affirmative effects of those three CPA is summarized. Health research is needed about those CPA and their effects on health law, policy and regulation in the United States and other nations.


Detection of an anhydride intermediate in the carboxypeptidase A catalyzed hydrolysis of a peptide substrate by solid state NMR spectroscopy and its mechanistic implication.
We have detected an anhydride intermediate in the CPA catalyzed proteolytic reaction of Gly-Tyr. It appears that since the zinc-bound water molecule which is believed to attack the scissile amide carbonyl carbon in the hydrolysis reaction is excluded by the N-terminal amino group of Gly-Tyr, the carboxylate of Glu-270 becomes to attack the amide bond to generate the anhydride intermediate.


Does prey preference change as a result of prey species being presented together? Analysis of prey selection by the predatory mite Typhlodromus pyri (Acarina: Phytoseiidae).
Prey-selection behaviour of the phytoseiid mite Typhlodromus pyri Scheuten was analysed with a Markovtype model of feeding-state dynamics and feeding-state dependent searching behaviour (Sabelis 1981, 1986, 1989; Metz and Van Batenburg 1985a, b). All behavioural characteristics of the predator which are independent of the feeding state were represented by one parameter. The remaining feeding-state dependent characteristics were represented by a function of the feeding state, with one parameter. The best parameter values to describe a predator-prey interaction were determined by fitting the model to the predation rates in monocultures. Under the assumption that the parameter values are not dependent on the composition of prey species supply, the diet of the predators in mixed cultures was predicted from parameters estimated in monoculture experiments.Two prey types, apple rust mite (Aculus schlechtendali (Nalepa)) adults and European red spider mite (Panonychus ulmi (Koch)) larvae were studied. A large discrepancy was observed between calculated and experimentally determined predation rates of T. pyri in mixed cultures: the predators actually killed 3-7 times more P. ulmi larvae than was predicted by the model.The large difference between observed and predicted predation rates in mixed cultures cannot be explained by changes in the behaviour of the prey species as a result of being together. Therefore, it seems likely that the prey selection behaviour of the predator was different when prey species were presented together than when presented singly. Apparently the predatory mite T. pyri prefers P. ulmi to S. schlechtendali.


Phyloevolutionary analysis of SARS-CoV-2 in Nigeria.
Phyloepidemiological approaches have provided specific insight into understanding the emergence and evolution of infection. Knowledge on the outbreak and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Nigeria would assist in provision of preventive measures to reduce transmission among populations at risk. This study aimed to investigate the evolution of SARS-CoV-2 in Nigeria. A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFlu™ database on 29 March 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the individual and the collection date. Other sequences were not selected because they were short, contained artefacts, were not from an original source or had insufficient information. Evolutionary history was inferred using the maximum likelihood method based on the general time reversible model. A phylogenetic tree was constructed to determine the common ancestor of each strain. The phylogenetic analysis showed that the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27 972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. The study evidently showed the entire outbreak of SARS-CoV-2 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.


High-dose thiotepa, in conjunction with melphalan, followed by autologous hematopoietic stem cell transplantation in patients with pediatric solid tumors, including brain tumors.
Among pediatric malignancies, solid tumors, particularly within the central nervous system (CNS), are common. Thiotepa, a myeloablative, high-dose chemotherapeutic (HDT) treatment administered prior to autologous hematopoietic stem cell transplantation (HSCT), can cross the blood-brain barrier and rapidly penetrate the CNS. We evaluated thiotepa HDT in conjunction with melphalan in Japanese patients with pediatric CNS/non-CNS solid tumors in a multicenter, open-label, non-comparative study. Thiotepa (200 mg/m2/day) was administered intravenously (IV) over 24 h on days -12, -11, -5, and -4 before scheduled HSCT. Melphalan (70 mg/m2/day) was administered IV over 1 h on days -11, -5, and -4. The safety analysis population comprised 41 patients, of whom 16 (39.0%) had solid tumors and 25 (61.0%) had brain tumors. The most frequently reported adverse events were diarrhea (40/41 [97.6%] patients) and febrile neutropenia (34/41 [82.9%]). No unexpected safety events were observed, and no events resulted in death or treatment discontinuation. All patients experienced bone marrow suppression and 39/41 (95.1%) achieved engraftment (neutrophil count ≥500/mm3 for 3 consecutive days after HSCT). The survival rate at day 100 post-autologous HSCT was 100%. These data confirm the safety of IV thiotepa plus melphalan HDT prior to autologous HSCT for patients with pediatric CNS/non-CNS solid tumors. Trial registration: JapicCTI-173654.


Configuration interaction study of the electronic states and spectroscopic properties of selenium monoxide.
The electronic spectrum of the selenium monoxide (SeO) molecule has been studied theoretically by using ab initio based multireference singles and doubles configuration interaction (MRDCI) methodology, which includes relativistic effective core potentials (RECP) and suitable Gaussian basis sets of the atoms. Potential energy curves of several electronic states correlating with the lowest and second dissociation limit are constructed. Spectroscopic parameters, namely Te, re, and ωe of 10 bound Λ-S states of the molecule within 4.71 eV are estimated and compared with the available data. In addition, binding energies of the ground and some excited states are computed. The changes in the potential energy curves and spectroscopic properties after the inclusion of the spin-orbit coupling are discussed and also compared with the available data. Transition probabilities of some dipole-allowed and spin forbidden transitions are estimated and radiative lifetimes of some excited states are reported. Dipole moments of some low-lying Λ-S states as a function of bond distance have also been computed.


Successful Isavuconazole therapy in a patient with acute invasive fungal rhinosinusitis and acquired immune deficiency syndrome.
To report a case of acute invasive Mucorales rhinosinusitis in a patient with acquired immune deficiency syndrome and diabetes mellitus. To provide a literature review on the role of Isavuconazole in the management of invasive Mucorales rhinosinusitis. A literature review was conducted on August 9, 2015 using PubMed database. The keywords isavuconazole and invasive fungal rhinosinusitis were employed to identify original scientific manuscripts that describe the use of Isavuconazole in patients with invasive fungal rhinosinusitis or rhinocerebral mucormycosis. The initial search yielded 35 articles with only 1 article (case report) describing the clinical use of Isavuconazole in a patient with invasive Mucorales rhinosinusitis. Acute invasive fungal rhinosinusitis is a rare, life-threatening infection with mortality rates reported to range from 30-83%. Successful treatment depends on early surgical debridement, systemic anti-fungal therapy, and correction of predisposing conditions. Isavuconazole (Cresemba), a newly approved antifungal, is safe and clinically effective in treating invasive mucormycosis. This important new therapy should be considered for patients with invasive Mucorales rhinosinusitis that is refractory or intolerant to Amphotericin B.


Suggested cutoff tumor size for management of small EUS-suspected gastric gastrointestinal stromal tumors.
Although the incidence of asymptomatic small gastric submucosal tumors increased gradually with routine medical health examination, there was little clinical evidence for management consensus in these small gastric submucosal tumors including endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs). We investigated the clinical course of small EUS-suspected gastric GISTs and propose a cutoff value of tumor size for treatment policy. In this retrospective study, 50 patients with EUS-suspected gastric GISTs of sizes less than 3 cm were enrolled and were followed up by EUS at least twice over a period of more than 24 months (range 24-101 months). An at least 20% increase of the maximal diameter of the tumors was set as a significant change. Significant changes in tumor size were found during the follow-up in 14 patients (28.0%). The one-dimensional 20% change corresponded well to 50% change in two-dimensional area measurement (correlation coefficient = 0.929). The receiver operating characteristic curve analysis showed that the best cutoff size, associated with tumor progression, was 1.4 cm having an 85.7% sensitivity, 86.1% specificity, and 86.0% accuracy. A larger tumor size (35.7% vs. 2.8%, p = 0.005) and irregular tumor margin on the EUS (71.4% vs. 0, p = 0.004) were two significant factors associated with the progression of tumor growth of small suspected gastric GISTs. Small EUS-suspected GISTs, larger than 1.4 cm, with irregular margin were associated with significant progression. This subgroup is suggested to be monitored by more intensive follow-up.


Sonorheometry versus rotational thromboelastometry in trauma: a comparison of diagnostic and prognostic performance.
Rotational thromboelastometry (ROTEM) is used to rapidly identify trauma-induced coagulopathy (TIC) and direct targeted interventions in hemorrhaging trauma patients. A novel technology, Quantra System (HemoSonics), utilizes sonic estimation of elasticity via resonance sonorheometry, avoids mechanical clot interference, and may increase diagnostic accuracy, but there are limited data on bleeding in major trauma patients. To compare the performance of Quantra with that of ROTEM for rapid diagnosis of TIC and prediction of transfusion requirements and mortality. Samples were collected from adult trauma patients enrolled in a perpetual cohort study upon admission to a single level 1 trauma center between 2020 and 2021. Samples were analyzed using Quantra, ROTEM, multiple electrode aggregometry, and conventional coagulation assays. Samples from 209 patients were analyzed. Correlations were strong between Quantra and ROTEM parameters (for all, p < .001): clot stiffness (CS) and tissue factor-activated ROTEM (EXTEM) clot amplitude at 5 minutes (A5) (r = 0.90); fibrinogen contribution to CS and tissue factor-activated ROTEM with cytochalasin D (FIBTEM) A5 (r = 0.85); and platelet contribution to CS and EXTEM-FIBTEM A5 (r = 0.73). Although CS showed higher discrimination than EXTEM A5 in detecting TIC (international normalized ratio, >1.2; area under the receiver operating characteristic curve, 0.83 vs 0.79; p = .038), the ability of fibrinogen contribution to CS to detect hypofibrinogenemia (a fibrinogen level of <2g/L) was good but lower than that of FIBTEM A5 (area under the receiver operating characteristic curve, 0.79 vs 0.84; p = .027). There was no difference between Quantra and ROTEM in detecting a platelet count of <150 × 109/L, predicting rapid transfusion or mortality at 6 hours. Quantra and ROTEM have similar diagnostic performances in evaluating TIC and predicting clinically relevant outcomes. Larger studies are required to determine the utility of Quantra for goal-directed treatment of TIC.


Transport and activation of S-(1,2-dichlorovinyl)-L-cysteine and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine in rat kidney proximal tubules.
An important step in understanding the mechanism underlying the tubular specificity of the nephrotoxicity of toxic cysteine conjugates is to identify the rate-limiting steps in their activation. The rate-limiting steps in the activation of toxic cysteine conjugates were characterized using isolated proximal tubules from the rat and 35S-labeled S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine (NAC-DCVC) as model compounds. The accumulation by tubules of 35S radiolabel from both DCVC and NAC-DCVC was time and temperature dependent and was mediated by both Na+-dependent and independent processes. Kinetic studies with DCVC in the presence of sodium revealed the presence of two components with apparent Km and Vmax values of (1) 46 microM and 0.21 nmol/mg min and (2) 2080 microM and 7.3 nmol/mg.min. NAC-DVVC uptake was via a single system with apparent Km and Vmax values of 157 microM and 0.65 nmol/mg.min, respectively. Probenecid, an inhibitor of the renal organic anion transport system, inhibited accumulation of radiolabel from NAC-DCVC, but not from DCVC. The covalent binding of 35S label to cellular macromolecules was much greater from [35S]DCVC than from NAC-[35S]DCVC. Analysis of metabolites showed that a substantial amount of the cellular NAC-[35S]DCVC was unmetabolized while [35S]DCVC was rapidly metabolized to bound 35S-labeled material and unidentified products. The data suggest that DCVC is rapidly metabolized following transport, but that activation of NAC-DCVC depends on a slower rate of deacetylation. The results are discussed with regard to the segment specificity of cysteine conjugate toxicity and the role of disposition in vivo in the nephrotoxicity of glutathione conjugates.


Analytical evaluation of current starch methods used in the international sugar industry: Part I.
Several analytical starch methods exist in the international sugar industry to mitigate starch-related processing challenges and assess the quality of traded end-products. These methods use iodometric chemistry, mostly potato starch standards, and utilize similar solubilization strategies, but had not been comprehensively compared. In this study, industrial starch methods were compared to the USDA Starch Research method using simulated raw sugars. Type of starch standard, solubilization approach, iodometric reagents, and wavelength detection affected total starch determination in simulated raw sugars. Simulated sugars containing potato starch were more accurately detected by the industrial methods, whereas those containing corn starch, a better model for sugarcane starch, were only accurately measured by the USDA Starch Research method. Use of a potato starch standard curve over-estimated starch concentrations. Among the variables studied, starch standard, solubilization approach, and wavelength detection affected the sensitivity, accuracy/precision, and limited the detection/quantification of the current industry starch methods the most.


Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma.
Vascular endothelial growth factor A (VEGF-A) and its receptor tyrosine kinases located on endothelial cells seem to play an important role in the multistep pathway of angiogenesis. SU5416 is a small molecule which inhibits angiogenesis by acting as an inhibitor of VEGF receptor-2 tyrosine kinase. We have developed a reproducible murine model for neuroblastoma, a childhood cancer, based on s.c. xenotransplantation of SH-SY5Y neuroblastoma cells. We found that SH-SY5Y cells expressed VEGF-A on both the mRNA and protein levels, that plasma concentrations of VEGF-A were significantly elevated in animals with neuroblastoma with a volume > 1.4 ml, and that there was a correlation between VEGF-A levels in plasma and tumor size in untreated tumor-bearing animals. Treatment with SU5416 reduced the growth of neuroblastoma tumors by 65% without apparent toxicity. SU5416 treatment also suppressed tumor angiogenesis, despite an increase in plasma VEGF-A levels per ml tumor volume during therapy. Our experimental data suggest that the angiogenesis inhibitor SU5416 may be beneficial in the treatment of solid tumors of childhood such as neuroblastoma.


Atlas of 99mTc-methylene diphosphonate renal images in pediatric oncology.
We describe the urinary tract abnormalities observed with bone scintigraphy during the evaluation of malignant disease. The possible abnormal renal patterns are discussed.


Does the cerebellum intervene in the abnormal somatosensory temporal discrimination in Parkinson's disease?
somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Altered STDT has been reported in Parkinson's disease (PD). The cerebellum seems to play a role in the pathophysiology of PD, and may consequently be involved in the pathophysiology of STDT abnormalities. STDT was investigated in fifteen PD patients who underwent real and sham cerebellar continuous theta burst stimulation (cTBS) in the OFF condition. Eight patients underwent a further real cTBS session in ON condition. STDT was measured on both hands before, 5 and 25 min after real and sham cTBS delivered over the cerebellar hemisphere ipsilateral to the more affected side. We controlled the efficacy of our protocol by monitoring primary motor cortex (M1) excitability. Ten healthy subjects acted as control group. STDT values were increased in PD patients in the OFF condition compared with healthy subjects and PD patients in the ON condition. In PD patients OFF condition, real but not sham cerebellar cTBS, significantly reduced STDT values only in the hand ipsilateral to the stimulated cerebellar hemisphere. Cerebellar cTBS also decreased motor evoked potentials (MEP) size in the contralateral M1. When PD patients were tested in the ON condition, cerebellar cTBS failed to modify STDT values. cerebellar cTBS improved STDT values in PD patients exclusively in OFF condition. We hypothesize that cerebellar stimulation partially compensates for increased STDT values only when patients are OFF dopaminergic therapy. This suggests that the cerebellum may act as compensatory system in PD.


The Phytochemical Constituents of Medicinal Plants for the Treatment of Chronic Inflammation.
Prolonged exposure to inflammatory mediators can lead to tissue damage, fibrosis, angiogenesis, and altered cellular metabolism [...].


Increasing exercise adherence among elderly patients with chronic disease in primary care: a prospective cohort study.
Currently, the evidence for exercise in maintaining health, well-being, and physical functioning is overwhelming. Despite these benefits, more than 50% of the population fails to meet the recommended exercise requirements for age and health status. In our study, we sought to provide a method to increase exercise adherence that was both effective and time-efficient for physicians and their patients. The primary objective of this research study was to evaluate the effectiveness of a graded exercise protocol and biweekly monitoring on increasing the duration of aerobic exercise to 150 min per week in a population of elderly individuals with chronic disease. Secondarily, we evaluated for improvement in resting heart rate, blood pressure, body mass index (BMI), and cardiorespiratory fitness. The overall study design was a randomized, prospective cohort study with assessor blinding. Forty-five patients aged ≥60 years with multiple comorbidities were recruited from the Internal Medicine Clinic at Wright-Patterson AFB. Participants were randomized into a treatment or control arm and observed over a period of 34 weeks. Those in the treatment arm were given a graded walking protocol and received biweekly phone calls to evaluate compliance. Those in the control arm did not receive an intervention or biweekly monitoring. Measurements of heart rate, blood pressure, and BMI were taken quarterly in both groups. At the beginning and conclusion of the study, each participant completed a modified Balke treadmill test and Physical Activity Scale for the Elderly (PASE). Continuous variables were evaluated with the independent samples t-test, whereas categorical variables were evaluated with the chi-squared test. A greater percentage of the treatment group achieved the primary outcome (41.6% vs. 0%; p = 0.003). Those in the treatment group also had favorable improvements in heart rate response (- 2.4 beats/min vs. + 5.3 beats/min; p = 0.038) and PASE (+ 66 vs.-20; p < 0.001). No significant differences were observed between groups for mean change in heart rate, blood pressure, or BMI. Guided, independent exercise and surveillance can be an effective tool in primary care practice to help patients reach the recommended levels of exercise for both age and health status.


The outcome of observation of acute traumatic extradural hemorrhage in pediatric age group.
The non-operative management of extradural hemorrhage in the pediatric age group has been increasingly considered in the last decade with good clinical outcomes and comparable results to surgical intervention in carefully selected patients. The purpose of this study is to evaluate the outcome of observation in the management of pediatric patients with extra dural hematoma. All consecutive pediatric patients with traumatic EDH after TBI who were presented to a single neurosurgical institution between January, 2008 and November, 2018 were retrospectively reviewed. Mechanism of injury, Glasgow coma scale (GCS) on admission, presenting neurological examination, treatment modality, the first and last imaging findings, and outcome were analyzed. The outcome was measured using the Glasgow outcome scale (GOS) on discharge from the hospital. A total of 83 patients were identified. The median age was 7.1 years (0.8-14 years) and 67% of the patients were male (n = 56). The median thickness of acute EDH was 1.1 cm (0.2-2.6 cm). 44 patients were managed conservatively with a close observation at a specialized neurotrauma unit for any clinical deterioration, and the remaining 39 patients were managed surgically. There was no significant difference in the patients age, hematoma thickness, presence of skull fractures, systemic injuries, and other types of cerebral injuries between the two groups. The presenting GCS was significantly lower in the surgical group which reflects the severity of the injury. Hospital stay was significantly longer among the surgical group, and the GOS was significantly better in the non-surgical group. The majority of the surgical group showed complete resolution of the hematoma on discharge, while only 50% of the non-surgical patients (n = 22) had a complete resolution of the hematoma one month after the TBI. The conservative management is applicable in carefully selected pediatric patients with acute traumatic extradural hematoma provided that the observation is accomplished in a well-established and equipped neurosurgical unit. These results are congruent with similar earlier studies.


Engineered rhizosphere: the trophic bias generated by opine-producing plants is independent of the opine type, the soil origin, and the plant species.
In a previous study, we demonstrated that transgenic Lotus plants producing opines (which are small amino acid and sugar conjugates) specifically favor growth of opine-degrading rhizobacteria. The opine-induced bias was repeated and demonstrated with another soil type and another plant species (Solanum nigrum). This phenomenon is therefore independent of both soil type and plant species.