Gastric Bypass Surgery Improves the Skeletal Muscle Ceramide/S1P Ratio and Upregulates the AMPK/ SIRT1/ PGC-1α Pathway in Zucker Diabetic Fatty Rats.
Roux-en-Y gastric bypass (RYGB) is associated with remission of type 2 diabetes. However, the cellular and molecular mechanisms remain unknown. We hypothesized that RYGB would increase peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), sirtuin-1 (SIRT1), AMPK/pAMPK, and citrate synthase (CS) protein expression and decrease insulin resistance and these changes would be mediated by sphingolipids, including ceramides and the sphingolipid metabolite sphingosine-1 phosphate (S1P). Male ZDF rats were randomized to RYGB (n = 7) or sham surgery (n = 7) and harvested after 28 days. Total tissue ceramide, ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1), and S1P were quantified in the white gastrocnemius muscle using LC-ESI-MS/MS after separation with HPLC. Total SIRT1, AMPK, PGC-1α, and CS protein expression were measured by Western blot. Body weight, fasting glucose, insulin, and HOMA-IR decreased significantly after RYGB compared with sham control. These changes were paralleled by lower total ceramide (483.7 ± 32.3 vs. 280.1 ± 38.8 nmol/g wwt), C18:0 ceramide subspecies (P < 0.05), higher S1P (0.83 ± 0.05 vs. 1.54 ± 0.21 nmol/g wwt, P < 0.05), and a lower ceramide/S1P ratio (P < 0.05) in the RYGB versus sham group. AMPK, pAMPK, SIRT1, PGC-1α, and CS protein expression was also higher after RYGB (P < 0.05). The ceramide/S1P ratio correlated with weight loss (r = 0.48, P = 0.08), insulin resistance (r = 0.61, P = 0.02), PGC-1α (r = - 0.51, P < 0.06), CS (r = - 0.63, P = 0.01), and SIRT1 (r = - 0.54, P < 0.04). Our data demonstrate that sphingolipid balance, and increased AMPK, SIRT1, PGC-1α, and CS protein expression are part of the mechanism that contributes to the remission of diabetes after RYGB surgery.


Inhibition-related differences between tic-free and tic-related obsessive-compulsive disorder: evidence from the N2 and P3.
Tic-related OCD (obsessive-compulsive disorder) was introduced as an OCD subtype in the DSM-5 based mainly on family and clinical data that showed differences between OCD in dependence of accompanying tics. Little is known, however, regarding neurocognitive differences between subtypes. We used the stop-signal task to examine whether differences exist in response inhibition between OCD patients without tics (n = 21), patients with tic-related OCD (n = 12), and 21 healthy controls. The groups were carefully matched for gender, age and level of education. The stop-signal reaction time (SSRT) and inhibition-related N2 and P3 were used to examine behavioral and neural correlates of response inhibition and inhibition-related processes. In the SSRT, no difference was found between groups. P3 amplitude was larger in tic-free compared to tic-related OCD and healthy controls. No group differences were found in the N2 amplitude. For tic-related OCD, SSRT data indicate intact response inhibition, and P3 data indicate intact neural aftereffects of inhibition like the evaluation of the outcome. This is similar to what is found in patients with TD and may, thus, be interpreted as a support for shared mechanisms in relation to TD. In OCD, alterations in P3 amplitude indicate hyperactivity in the evaluation of the outcome of the inhibition process. This is in line with hyperactivity generally found in performance monitoring in OCD.


Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort.
Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28). Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.


Improving response to out-of-hospital cardiac arrest: The verified responder program pilot.
Survival following out-of-hospital cardiac arrest (OHCA) decreases as the interval from collapse to CPR and defibrillation increases. Innovative approaches are needed to reduce response intervals, especially for private locations. We undertook the Verified Responder Program in 5 United States communities during 2018, whereby off-duty EMS professionals volunteered and were equipped with automated external defibrillators (AEDs). Volunteers were alerted using a geospatial smartphone application (PulsePoint) and could respond to nearby private and public suspected OHCA. The study evaluated the frequency of Verified Responder notification, response, scene arrival, and initial care prior to EMS arrival. OHCA surveillance used the CARES registry. Of the 651 OHCA events (475 private, 176 public), Verified Responders were notified in 7.4% (n = 49). Among the 475 in a private location, volunteers were alerted in 8% (n = 38), responded in 2.7% (n = 13), arrived on scene in 2.3% (n = 11), and provided initial care in 1.7% (n = 8). Among the 176 in a public location, volunteers were alerted in 6.3% (n = 11), responded in 2.3% (n = 4), arrived on-scene in 2.3% (n = 4), and provided initial care in 2.3% (n = 4). Over 96% surveyed had positive impression of the program and intended to continue participation. No responder reported any adverse event. In this initial US-based experience of a smartphone program for suspected OHCA in private and public locations, Verified Responders reported a positive experience, though were only involved in a small fraction of OHCA. Studies should determine how this type of program could be enhanced to involve more OHCA events.


Image-guided ablation of painful metastatic bone tumors: a new and effective approach to a difficult problem.
Painful skeletal metastases are a common problem in cancer patients. Although external beam radiation therapy is the current standard of care for cancer patients who present with localized bone pain, 20-30% of patients treated with this modality do not experience pain relief, and few further options exist for these patients. For many patients with painful metastatic skeletal disease, analgesics remain the only alternative treatment option. Recently, image-guided percutaneous methods of tumor destruction have proven effective for treatment of this difficult problem. This review describes the application, limitations, and effectiveness of percutaneous ablative methods including ethanol, methyl methacrylate, laser-induced interstitial thermotherapy (LITT), cryoablation, and percutaneous radiofrequency ablation (RFA) for palliation of painful skeletal metastases.


Into the fourth dimension.
The influence of time on the drought response of Brassica rapa, an agriculturally important species of plant, has been clarified.


Luminescent ZnO quantum dots for sensitive and selective detection of dopamine.
Water-soluble and luminescent ZnO quantum dots (QDs) capped by (3-aminopropyl) triethoxysilane (APTES) are environment-friendly with strong photoluminescence (max. wavelength: 530 nm). Interestingly, it was found that the fluorescence could be quenched by dopamine (DA) directly. On the basis of above, a novel ZnO QDs based fluorescent probe has been successfully designed to detect DA with high selectivity and sensitivity. Moreover, the possible fluorescence quenching mechanism was proposed, which showed that the quenching effect may be caused by the electron transfer from ZnO QDs to oxidized dopamine-quinone. Under optimum conditions, the relative fluorescence intensity was linearly proportional to the concentration of DA within the range from 0.05 to 10 μM, with the detection limit down to 12 nM (n=3). Also, the selectivity experiment indicated the probe had a high selectivity for DA over a number of possible interfering species. Finally, this method was successfully used to detect DA in serum samples with quantitative recoveries (99-110%). With excellent selectivity and high sensitivity, it is believed that the ZnO QDs based fluorescent probe has a potential for the practical application in clinical analysis.


Formulary management of recombinant factor VIIa at an academic medical center.
Recombinant human coagulation factor VIIa (rVIIa) is a procoagulant indicated for treatment of bleeding in patients with hemophilia. A large proportion of rVIIa utilization is for off-label administration in nonhemophiliac patients with acute hemorrhage. Concerns of potentially inappropriate use, safety, and cost of rVIIa led to efforts to standardize use of this agent. To comparatively describe the utilization of rVIIa upon implementation of an evidence-based guideline at a university hospital. With advisory direction from a multidisciplinary task force, an evidence-based guideline for use of rVIIa was developed, approved, and fully implemented. Assessment of appropriateness of use and retrospective review were required for all cases. Effects of these actions were evaluated by auditing and comparing rVIIa use in patients treated in two 6-month observation periods before and after guideline implementation. Outcomes assessed were proportions of patients deemed appropriate to receive rVIIa, compliance with dosing recommendations, and acquisition costs. Twenty-two and 29 patients were treated in the periods before and after guideline implementation, respectively. Patient characteristics were similar, except more cardiothoracic surgeries were performed in patients treated before implementation of the guideline. Indications for rVIIa use were judged appropriate in 21 (95.5%) before-cases and in all (100%) after-cases. The dose was compliant in 1 (4.6%) before-case and 27 (93.1%) after-cases (p < 0.001). Mean dosages of rVIIa administered were 81.8 microg/kg and 45.3 microg/kg in before- and after-cases, respectively (p < 0.001). During the respective periods of observation, amounts of rVIIa purchased monthly averaged 42.6 mg and 21.8 mg, a 49% difference. Semiannual expenditures for rVIIa decreased approximately $110,000 following guideline implementation. Patient outcomes were similar. A guideline based on currently available evidence can serve to sustain the clinical appropriateness of rVIIa therapy and substantially decrease costs.


Microscopic findings of the nail-fold capillaries--dependence on menopausal status and hormone replacement therapy.
The aim of our controlled study was to evaluate peripheral microcirculation at the level of the nail-fold capillaries in relation to menopause status and postmenopausal hormone replacement therapy (HRT). A total of 105 postmenopausal women were randomly allocated to three different HRT groups of equal size. A fourth group of 35 similar healthy volunteers served as controls. HRT was either peroral or transdermal 17-beta-oestradiol with cyclic addition of dydrogesterone or 2.5 mg Tibolone (Org OD 14) in a daily peroral dose. Morphological parameters such as capillary diameters, loop width, papillary width and capillary density, measured by video-capillaroscopy at the nail-fold, were unaffected in early menopause and also under HRT. A significant decrease of capillary blood flow velocity (P < 0.001) could be demonstrated in postmenopausal (n = 41, v = 0.53 +/- 0.16 mm/s) as compared to premenopausal women (n = 37, v = 0.65 +/- 0.15 mm/s). HRT resulted in an increase of capillary blood flow velocity in the nail-fold after 6 and 12 months leading to an increase in capillary blood flow in the order of 20%-30% of the initial values, and was independent of the type of HRT.


Release of mouse eggs from metaphase arrest by protein synthesis inhibition in the absence of a calcium signal or microtubule assembly.
Mouse egg activation, which includes release from meiotic metaphase II arrest, results from fertilization-induced increase in intracellular calcium concentration ([Ca2+]i). However, during egg activation caused by exposure to the protein synthesis inhibitor, cycloheximide, [Ca2+]i did not change. Although eggs fertilized in the presence of microtubule inhibitors remain arrested at metaphase, eggs treated for 32 hr with cycloheximide and the microtubule inhibitor, colcemid, formed nuclei. In untreated eggs aged in culture for 24 hr, the microtubule spindles became deformed. These eggs formed nuclei after exposure to cycloheximide, but not the calcium ionophore A23187. Our results indicate that eggs in which protein synthesis is inhibited are released from metaphase without an increase in [Ca2+]i, and despite disruption of the spindle.


Implementing psychiatric day treatment for infants, toddlers, preschoolers and their families: a study from a clinical and organizational perspective.
An increasing number of empirical studies indicate that infants, toddlers and preschoolers may suffer from non-transient mental illnesses featuring developmental psychopathology. A few innovative child psychiatric approaches have been developed to treat infants, toddlers and preschoolers and their families, but have not yet been conceptually presented and discussed in the framework of different healthcare systems. The organizational and clinical experience gained while developing specific approaches may be important across disciplines and guide future developments in psychiatric treatment of infants, toddlers, preschoolers and their families. This article introduces the Preschool Family Day Hospital for Infants, Toddlers and Preschoolers and their Families at Münster University Hospital, Germany. This hospital is unique in the German healthcare system with regard to its social-service institution division of labor. Specifically, it uses an intermittent treatment approach and an integrated interactional family psychiatric approach to treat children and their parents as separate patients. This multidisciplinary, developmentally and family-oriented approach includes components of group treatments with children and separate treatments with parents. Specific techniques include video-assisted treatments of the parent-child interaction, psychiatric and psychotherapeutic treatments for parents, and conjoint family therapies that include both parents and siblings. The Family Day Hospital for infants, toddlers and preschoolers and their families offers innovative family-oriented treatments for those who suffer from a wide range of severe child psychiatric disorders that cannot be sufficiently treated in outpatient settings. Treatment is based on the need for family-oriented approaches to the early psychiatric treatment of infants, toddlers and preschoolers. Family day hospitals are an innovative approach to preschool child psychiatry that requires further evaluation.


[Nutrient characteristics in leaves of broadleaved seedlings in south China].
Nutrient concentrations and contents in leaves of broadleaved Elaeocarpus sylvestris, Castanopsis hystrix, Ormosia pinnata, Michelia macclurei, Camellia semiserata, Liquidambar formosana, Castanopsis fissa, Mytilaria laosensis and Cinnamomum camphora seedlings were studied. Leaf N, P and K concentrations in Ormosia pinnata, Castanopsis fissa and Cinnamomum camphora were higher than those of other tree species, and leaf N, P and K contents in Camellia semiserata, Castanopsis fissa and Cinnamomum camphora were higher than those of other tree species. Mean leaf nutrient concentration in upper crown and lower crown of 9 tree species was N 16.67 and 17.09 g.kg-1, P 1.29 and 0.84 g.kg-1, K 11.77 and 6.65 g.kg-1, respectively. Mean leaf nutrient content in upper crown and lower crown of 9 tree species was N 0.871 and 1.069 g.m-2, P 0.065 and 0.052 g.m-2, K 0.608 and 0.426 g.m-2, respectively. Leaf P and K concentrations and contents in the upper crown were generally higher than those of the lower crown. From the view of nutrient contents, mixing Camellia semiserata with other tree species, mixing Castanopsis hystrix or Mytilaria laosensis with Elaeocarpus sylvestris, Liquidambar formosana, Ormosia pinnata, Castanopsis fissa, and Cinnamomum camphora, and mixing Michelia macclurei with Castanopsis fissa and Cinnamomum camphora were suitable.


Investigation of melanoma-associated antigen A4 cancer/testis antigen clinical relevance in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is considered as the seventh most common cancer worldwide, and the second prevalent malignancy in the north of Iran. A subfamily group of tumor-specific antigens, commonly specified as cancer/testis antigens (CTAs), are expressed restrictedly in testis, ovary, and placenta. Melanoma-associated antigen A4 (MAGEA4) as a CTA is overexpressed in a variety of cancers. Expressional analysis of MAGEA4 protein in ESCC may be useful to investigate its clinical relevance leading to effective improvements in ESCC diagnosis and treatment. Fifty-six ESCC patients with no preoperative therapeutic circumstance such as radiotherapy or chemotherapy were analyzed to explore the protein expression level of MAGEA4 using immunohistochemistry assay. MAGEA4 overexpression was detected in 66% of ESCC samples showing strong nuclear and cytoplasmic staining compared to the normal epithelium. There were significant correlations between MAGEA4 protein expression and depth of tumor invasion (P = 0.019), and the number of involved lymph nodes (P = 0.045). Because of the significant correlation of MAGEA4 and indices of poor prognosis, the role of this CTA may be confirmed in ESCC aggressiveness and metastasis. Therefore, MAGEA4 may be a promising therapeutic candidate for suppressing ESCC aggressiveness.


Dopamine autoreceptor agonists including CGS 15855A decrease dopamine release and metabolism in mouse brain.
The ability of dopamine autoreceptor agonists to suppress the in vivo release or metabolism of dopamine in mouse brain was determined by measuring steady state levels of 3-methoxytyramine (3-MT) or dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), respectively. These experiments provide the first neurochemical evidence for dopamine autoreceptors in the mouse. (-)N-n-propylnorapomorphine, apomorphine, (+)-3-PPP, TL-99, and the novel dopamine autoreceptor agonist CGS 15855A each decreased 3-MT levels at doses that approximated their potency in the gamma-butyrolactone model. CGS 15855A suppressed dopamine release and metabolism to the same extent in the rat and mouse neostriatum. Generally, agonist-induced decreases in 3-MT levels were obtained to a greater extent or with lower doses than were changes in DOPAC or HVA. The autoreceptor efficacy of CGS 15855A was confined to the (+) and not the (-) optical isomer. Consecutive injections of CGS 15855A did not induce an acute tolerance to its actions but instead prolonged for at least 3.5 h the suppression of dopamine metabolism and release. The release and metabolism of dopamine in mouse limbic and striatal regions is regulated by autoreceptors with a pharmacological specificity that is similar to autoreceptors of the rat.


The safety and efficacy of tolvaptan in the treatment of patients with autosomal dominant polycystic kidney disease: A systematic review and meta-analysis.
The irreversible progression of autosomal dominant polycystic kidney disease (ADPKD) to end-stage renal disease (ESRD) is delayed by tolvaptan. Therefore, we aim to systematically estimate and evaluate the efficacy and safety of tolvaptan in the treatment of ADPKD. Two reviewers independently searched all published randomized controlled trials studies in PubMed, EMBASE, Web of Science and Cochrane databases, extracted data, assessed bias risk and rated the quality of evidence. Data were analyzed by the RevMan software. We identified 8 trials including 2135 patients. Both of the decline of estimated glomerular filtration rate (eGFR) [MD=1.89, 95% CI (0.74, 3.04), P=0.001] and total kidney volume (TKV) [MD=-3.32, 95% CI (-4.57, -2.07), P<0.001] were delayed in tolvaptan group compared with placebo group in ADPKD patients. The use of tolvaptan delayed TKV progression in the different-month subgroups [MD=-69.99, 95% CI (-91.05, -48.94), P<0.001]. Tolvaptan reduced renal pain [RR=0.66, 95% CI (0.54, 0.81), P<0.001] and hematuria events [RR=0.55, 95% CI (0.41, 0.74), P<0.001] in ADPKD patients. However, the prevalence of thirst [RR=2.75, 95% CI (2.34, 3.24), P<0.001] and nocturia events [RR=3.01, 95% CI (1.27, 7.11), P=0.01] were increased in tolvaptan group. There is no significant difference of hypertension events [RR=0.92, 95% CI (0.82, 1.03), P=0.13] in tolvaptan group compared placebo group. This meta-analysis suggests that tolvaptan may improve clinical progression in patients with ADPKD without significantly increasing the risk of adverse reactions.


HPLC methods for studying pharmacokinetics of tivozanib and in vitro metabolic interaction with dexamethasone in rat.
Tivozanib is a recently approved tyrosine kinase inhibitor for the treatment of renal cell carcinoma. In this work, two new HPLC methods coupled with fluorescence (FLD), or photodiode array detectors (PDA) were developed and used for the first time for tivozanib quantification in rat plasma and liver microsomes. The described methods were efficient with a 4-min runtime employing a Gemini-NX C18 column (50 × 2.1 mm, 3 µm) and a mobile phase of acetonitrile and ammonium acetate buffer (pH 4.7, 10 mM) (40:60, v/v) delivered at a flow rate of 0.4 mL/min. The use of HPLC-FLD allowed the quantification of 50 ng/ mL tivozanib using only 100 µL rat plasma. The HPLC-FLD method was validated according to the US food and drug administration (FDA) bioanalytical guidelines and was applied successfully in a rat pharmacokinetic study (n = 7) following oral administration of 1 mg/ kg tivozanib. Furthermore, HPLC-PDA was used for monitoring the depletion of 1 μM (454.9 ng/mL) tivozanib in rat liver microsomes and was applied to study the effect of dexamethasone induction on tivozanib metabolism in vitro. Results showed that dexamethasone enhanced the intrinsic clearance of tivozanib by 60 % suggesting a potential drug-drug interaction at the metabolism level. Dexamethasone is commonly used in the management of cancer disease and thus coadministration with tivozanib therapy may cause treatment failure in patients. The simplicity, speed and cost-effectiveness of the reported methods are ideal for supporting in vivo and in vitro tivozanib studies, including drug-drug interaction studies, particularly in bioanalytical labs lacking LC-MS/MS capabilities.


A comprehensive guide of remediation technologies for oil contaminated soil - Present works and future directions.
Oil spills result in negative impacts on the environment, economy and society. Due to tidal and waves actions, the oil spillage affects the shorelines by adhering to the soil, making it difficult for immediate cleaning of the soil. As shoreline clean-up is the most costly component of a response operation, there is a need for effective oil remediation technologies. This paper provides a review on the remediation technologies for soil contaminated with various types of oil, including diesel, crude oil, petroleum, lubricating oil, bitumen and bunker oil. The methods discussed include solvent extraction, bioremediation, phytoremediation, chemical oxidation, electrokinetic remediation, thermal technologies, ultrasonication, flotation and integrated remediation technologies. Each of these technologies was discussed, and associated with their advantages, disadvantages, advancements and future work in detail. Nonetheless, it is important to note that no single remediation technology is considered the best solution for the remediation of oil contaminated soil. This review provides a comprehensive literature on the various remediation technologies studied in the removal of different oil types from soil.


Insecticide-treated bed net utilization and associated factors among pregnant women in Ethiopia: a systematic review and meta-analysis.
Malaria infection during pregnancy endangers the pregnant woman, fetus, and newborn child. Thus, the use of an insecticide-treated net (ITN) is one of the most frequently advised methods for preventing malaria during pregnancy. Contrary findings have been reported in various studies on ITN utilization among pregnant women in Ethiopia. Therefore, this study was aimed to estimate the pooled prevalence of ITN utilization and its associated factors among pregnant women in Ethiopia. Published articles from PubMed, Google Scholar, Science Direct, AJOL and Cochrane library were systematically searched. All cross-sectional studies on ITN utilization among pregnant women were included in this meta-analysis. To estimate the pooled prevalence and odds ratio, a random-effect model was used; and a subgroup analysis was performed to identify the possible source of heterogeneity. Begg's and Egger's tests were used to identify possible publication bias. Ten cross-sectional studies with 7,161 participants were included. The pooled prevalence of ITN utilization among all pregnant women who had access to ITN in Ethiopia was 59.42% (95% CI 51.14, 67.69). Statistically significant heterogeneity was observed (I2 = 97.7%; p < 0.0001). Higher educational status (OR = 3.47, 95% CI 2.32, 5.2), pregnant women who had antenatal care visits (OR = 2.37, 95% CI 1.97, 2.65) and having good knowledge of malaria prevention practices (OR = 10.63, 95% CI 5.31, 21.29) were associated with ITN utilization among pregnant women. The utilization of ITNs among pregnant women was much lower than the national target. Higher education status, attending ANC and a good level of knowledge were found to be independent predictors of ITN utilization. Improving women's understanding of ITNs will enhance their use, and the government and health sectors should encourage pregnant mothers to enroll in antenatal care.


Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S): psychometric properties of a brief scale for cognitive evaluation in schizophrenia.
The Screen for Cognitive Impairment in Psychiatry (SCIP) is a brief scale designed for detecting cognitive deficits in several psychotic and affective disorders. This study examined the psychometric properties of the Spanish version of the SCIP in a sample of outpatients suffering schizophrenia-spectrum disorders. Psychometric properties were evaluated in a sample of 126 stable patients with schizophrenia. Men and women 18 to 55 years of age were recruited from consecutive admissions to 40 psychiatric outpatient clinics in Spain and asked to complete a series of cognitive measures at baseline, as well as three versions of the SCIP separated by one week intervals. A matched sample of 39 healthy controls was also subjected to the baseline examination. The feasibility, reliability and validity of the SCIP was examined; concurrent validity was assessed by means of a complete neuropsychological battery. Average time for SCIP administration was 16.02 (SD=5.01) minutes. Test-retest reliability intra-class correlation coefficients ranged from 0.74 to 0.90, with an internal consistency Cronbach's alpha value of 0.73. The three parallel forms of SCIP were shown to be equivalent. The SCIP scales were correlated with corresponding neuropsychological instruments, with Pearson's r between 0.38 and 0.60, p<0.01. The SCIP effectively discriminated between the patient and control samples. Factor analysis revealed one significant dimension, cognitive performance, that accounted for 49.8% of the total variance. The Spanish version of the SCIP is a simple, brief, valid and reliable tool for detection of cognitive impairment in patients with schizophrenia by minimally trained healthcare personnel.


Focal and generalized EEG paroxysms in childhood absence epilepsy: topographic associations and distinctive behaviors during the first cycle of non-REM sleep.
To better understand the nature of the focal spike-wave discharges (FSWDs) and focally led generalized spike-wave discharges (GSWDs) in typical childhood absence epilepsy (CAE) and by implication their nosologic and taxonomic significance. Twenty-four abnormal video-electroencephalography (EEG) studies from 13 consecutive children with CAE and good response to appropriate antiepileptic drugs (AEDs) were analyzed. We studied the association between the topography of absence onset and the ictal automatisms, and the topographic correlation between FSWDs and GSWDs and their respective behavior during hyperventilation and the different states of phasic and nonphasic non-rapid eye movement (NREM) sleep. GSWDs were considered as of "focal" onset if a lead-in could be visibly recognized at a paper speed of 60 mm/s, and were classified by their topography. (1) Multifocal absences occurred in 10 children; anterior onset was noted in 81 absences (73.6%) from 12 children and posterior in 18 (16.4%) from 7 children; there was no association between topography of absence onset and ictal automatisms; (2) FSWDs occurred in 85% of children and were multifocal in 73% of them; 85% of FSWDs were anterior and 14% posterior; (3) there was good topographic association between FSWDs and the leading spike of GSWDs of "focal" onset in all children with FSWDs; (4) both FSWDs and GSWDs increased during hyperventilation; (5) FSWDs occurred mainly during noncyclical NREM sleep and during periods of reduced vigilance of cyclical NREM sleep, whereas GSWDs occurred during the periods of enhanced vigilance of NREM sleep; GSWDs occurred significantly more frequently than FSWDs at the transition from reduced to enhanced vigilance of NREM sleep. Our findings suggest that in CAE focal EEG paroxysms reflect a system of multifocal nonlocalizing electrically unstable cortical areas that under the facilitatory influence of exogenous or endogenous factors like sleep instability can foster a corticothalamic response of sufficient strength to generate 3-Hz GSWDs that are conditionally sustainable and potentially ictal. FSWDs can be viewed as incomplete forms of the GSWDs; together they define the EEG identity of idiopathic "generalized" epileptogenesis.


Lipase immobilization on high water adsorbing capacity bagasse: applications in bio-based plasticizer synthesis.
This study investigates the structure and water adsorbing capacity of bagasse and of sodium hydroxide pretreated bagasse. The structures of bagasse and bagasse-NaOH were compared by SEM and XRD. Candida antarctica lipase B was then immobilized on bagasse, bagasse-NaOH and DPA@bagasse-NaOH. The expressed activity and immobilization yield of lipase immobilized on bagasse-NaOH (1.0%) was 36% and 45% higher than that on bagasse. When dopamine (DPA) was used as cationic polymer monomer via self-polymerization for mediating immobilization, the protein loading amounts and activity of lipase immobilized on DPA@bagasse-NaOH were higher than that of bagasse-NaOH. When the DPA concentration was 100 mg/ml, the immobilized lipase expressed activity reached its highest value (800 U/g), where the immobilization yield achieved 96.8%, which was 3.93-fold of lipase immobilized on native bagasse (24.6%). Then the immobilized lipases were used to synthesize a bio-based plasticizer. Lipase immobilized on DPA@bagasse-NaOH exhibited a significantly improved operational stability. Even after 12 batches, a high ester yield (84.2%) was maintained. Additionally, poly (vinyl chloride) PVC blends plasticized with methyl oleate as a secondary plasticizer were investigated. It was discovered that methyl oleate can be used as an effective bio-based plasticizer for PVC. These results indicate that bagasse with high water adsorbing capacity and self-polymerized DPA layer could create a favorable microenvironment for bio-based plasticizer synthesis in esterification reactions.


Self-efficacy in bipolar disorder: Development and validation of a self-report scale.
Successful management of bipolar disorder (BPD) typically involves individuals undertaking a complex array of self-management tasks (e.g., taking medication, monitoring symptoms, following a regular sleep routine). Many people with BPD doubt they can successfully undertake these tasks. This low sense of self-efficacy may lead to the perpetuation of BPD symptoms, poor quality of life, and low adherence to treatment. Research on self-efficacy in BPD has been hampered by the lack of a short, reliable and valid self-report scale that is practical to use in clinical and research settings. We sought to develop such a scale. BPD patients (N = 303) completed a new battery of items measuring their self-efficacy for performing BPD self-management tasks. Modern psychometric techniques such as bifactor analyses were used to refine the scale, determine an appropriate scoring algorithm, and establish reliability and validity. The Bipolar Self-Efficacy Scale (BPSES) comprises 17 items. BPSES scores were reliable, sensitive to change, and correlated with theoretically related constructs such as social adjustment and positive affect. BPSES scores had substantially higher associations with depression and quality of life than an alternative instrument that measured self-efficacy in general, rather than self-efficacy specifically related to bipolar disorder self-management. Patients were required to be medically managed while attending adjunctive psychological treatment of BPD. The BPSES is a brief scale that can be used to reliably and validly measure bipolar self-efficacy. It may be fruitful to use the scale in clinical practice, and studies investigating treatment outcomes, mechanisms, and moderators.


Quality of life and toxicity of stereotactic radiotherapy in pancreatic tumors: a case series.
To analyze the results of extracranial stereotactic radiotherapy (ESRT) experience in pancreatic cancer patients. Four noncoplanar fixed beams were used in all patients. Analysis of 16 patients was carried out. Overall response rate was 56.2%. Fifteen patients experienced local and/or distant progression of disease (median follow-up: 24 months). Two-year local progression-free, distant progression-free, and overall survivals were 85.7%, 58.7%, and 50.0%, respectively. Toxicity was less than grade 2 in all, although 1 patient had severe duodenal bleeding. Quality of life scores were unchanged. ESRT was associated with low complication rate, and not worsening the patients' quality of life.


Erratum: Long Noncoding RNA GAS5 Acts As A Tumor Suppressor In Laryngeal Squamous Cell Carcinoma Via miR-21 [Corrigendum].
[This corrects the article DOI: 10.2147/CMAR.S213690.].


Hedgehog signaling regulates regenerative patterning and growth in Harmonia axyridis leg.
Appendage regeneration has been widely studied in many species. Compared to other animal models, Harmonia axyridis has the advantage of a short life cycle, is easily reared, has strong regeneration capacity and contains systemic RNAi, making it a model organism for research on appendage regeneration. Here, we performed transcriptome analysis, followed by gene functional assays to reveal the molecular mechanism of H. axyridis leg regenerative growth process. Signaling pathways including Decapentaplegic (Dpp), Wingless (Wg), Ds/Ft/Hippo, Notch, Egfr, and Hedgehog (Hh) were all upregulated during the leg regenerative patterning and growth. Among these, Hh and its auxiliary receptor Lrp2 were required for the proper patterning and growth of the regenerative leg. The targets of canonical Hh signaling were required for the regenerative growth which contributes to the leg length, but were not essential for the pattern formation of the regenerative leg. dpp, wg and leg developmental-related genes including rn, dac and Dll were all regulated by hh and lrp2 and may play an essential role in the regenerative patterning of the leg.


Pseudogene AKR1B10P1 enhances tumorigenicity and regulates epithelial-mesenchymal transition in hepatocellular carcinoma via stabilizing SOX4.
Pseudogenes exert potential functions in tumorigenicity and tumour process in human beings. In our previous research on oncogene AKR1B10 in hepatocellular carcinoma (HCC), its pseudogene, AKR1B10P1, was preliminarily noticed being anomalistic transcribed, whereas whether AKR1B10P1 plays any specific function in HCC is poorly understood. By using shRNA transfection and lentiviral infection, we regulated the expression of ARK1B10P1 transcript and the relative targets in two ways. As we discovered, pathological transcription of AKR1B10P1 in HCC cells significantly promotes cell growth and motility either in vitro or in vivo. AKR1B10P1 was correlated with relatively dismal features of HCC. The epithelial-mesenchymal transition (EMT) was enhanced by up-regulating AKR1B10P1. And, a potential sequence of AKR1B10P1 transcript was discovered directly interacting with miR-138. SOX4, a pivotal promotor of EMT, was validated as the down-streaming target of miR-138. Mechanistically, degradation of SOX4 mRNA induced by miR-138 was effectively abrogated by AKR1B10P1. In conclusion, pseudogene AKR1B10P1 exerts stabilizing effect on SOX4 in HCC, associated EMT process, by directly sponging miR-138, which post-transcriptionally modulates SOX4's regulating gene.


Prognostic impact of the radiological infiltrative feature of primary renal tumor in metastatic renal cell carcinoma.
Recent studies suggest that the radiological infiltrative feature (r-IF) of renal tumors is strongly correlated with poor oncologic outcomes in locally advanced renal cell carcinoma (RCC). This study investigated the prognostic impact of r-IF of primary renal tumors in metastatic RCC (mRCC) in comparison with International Metastatic RCC Database Consortium (IMDC) risk model. We retrospectively analyzed 91 patients with previously untreated mRCC. Dynamic computed tomography of the primary renal tumor was reviewed to assess r-IF, defined as a focally/extensively ill-defined tumor interface with normal renal parenchyma. The median age was 67 years, and 69 patients (76%) were men. Prior nephrectomy was performed in 47 patients (52%). The median size of the primary renal tumor was 6.7 cm, and 50 patients (55%) presented with cT3-4 stage. Overall, 25 (28%)/52 (57%)/14 (15%) patients were classified into IMDC favorable/intermediate/poor-risk groups, respectively. An image review identified r-IFs in the primary renal tumor in 40 patients (44%). The incidences of r-IFs were 28%/46%/64% in IMDC favorable/intermediate/poor-risk groups, respectively. During a median follow-up of 2.6 years, 31 patients (34%) died of RCC. On multivariable analysis, r-IF and IMDC intermediate-poor risks were independently associated with poor cancer-specific survival (CSS). Two-year CSS were 64%/87% in patients with/without r-IF, respectively. C-index was improved from 0.73 to 0.81 by adding r-IF to the IMDC risk factors. R-IF of the primary renal tumor was an independent risk factor for poor CSS in patients with mRCC, which may improve the prognostic accuracy when combined with the IMDC risk model.


Focal myositis and its differential diagnosis. A case report and review of the literature.
A 55 year-old woman underwent a wide surgical excision because a left thigh mass. The histopathological study showed a focal myositis of the vastus lateralis muscle. The patient remains asymptomatic after four years follow-up. The differential diagnosis with soft tissue sarcomas and other inflammatory myopathies is discussed.


Dysfunction of the heme recycling system in heme oxygenase 1-deficient mice: effects on macrophage viability and tissue iron distribution.
To better understand the tissue iron overload and anemia previously reported in a human patient and mice that lack heme oxygenase-1 (HO-1), we studied iron distribution and pathology in HO-1(Hmox1)(-/-) mice. We found that resident splenic and liver macrophages were mostly absent in HO-1(-/-) mice. Erythrophagocytosis caused the death of HO-1(-/-) macrophages in in vitro experiments, supporting the hypothesis that HO-1(-/-) macrophages died of exposure to heme released on erythrophagocytosis. Rupture of HO-1(-/-) macrophages in vivo and release of nonmetabolized heme probably caused tissue inflammation. In the spleen, initial splenic enlargement progressed to red pulp fibrosis, atrophy, and functional hyposplenism in older mice, recapitulating the asplenia of an HO-1-deficient patient. We postulate that the failure of tissue macrophages to remove senescent erythrocytes led to intravascular hemolysis and increased expression of the heme and hemoglobin scavenger proteins, hemopexin and haptoglobin. Lack of macrophages expressing the haptoglobin receptor, CD163, diminished the ability of haptoglobin to neutralize circulating hemoglobin, and iron overload occurred in kidney proximal tubules, which were able to catabolize heme with HO-2. Thus, in HO-1(-/-) mammals, the reduced function and viability of erythrophagocytosing macrophages are the main causes of tissue damage and iron redistribution.


Adipose-specific inactivation of thyroid stimulating hormone receptors in mice modifies body weight, temperature and gene expression in adipocytes.
In obesity, the expression level of thyroid stimulating hormone receptor in adipose tissue is reduced and the levels of thyroid stimulating hormone (TSH) are often elevated within the normal range. To investigate the role of TSHR in brown and white adipose tissue (AT) using TSHR knockout (KO) mice and the physiological phenotypes affected by the TSHR knockout. AT-specific TSHR KO male mice and wild type (WT) controls were given a high-fat diet (HFD) or a control diet (CD). Body weights and food consumption were recorded for 20 weeks and body temperatures for the first 3 weeks. At termination, white and brown adipocytes were isolated. Gene expressios was investigated using real-time PCR. In a subgroup of female KO mice, glucose tolerance was investigated. TSHR were partially knocked out in KO mice, which gained more weight than WT mice when fed both a CD (p = .03) and HFD (p = .003). Body temperatures were lower in KO mice on CD (p <.001) and on HFD (p <.001) than WT controls. This was in agreement with reduced gene expression of UCP1 in brown adipocytes in the KO mice. Glucose tolerance was significantly impaired in KO mice on CD mice before termination (p <.01). Expression of adipogenic and lipolytic genes were reduced in KO mice, which was exacerbated by HFD. The mRNA levels of adipokines including ADIPOQ and LEP were altered in white adipocytes of KO mice. TSHR KO led to dysfunction of both white and brown AT and predisposition to excess body weight gain in mice. Our data show that TSHR in AT regulates glucose tolerance, lipid metabolism, adipokine profile, and thermogenesis.


Correlation between microscopical changes and Tau 64 and 69 biochemical detection in senile dementia of the Alzheimer type. Tau 64 and 69 are reliable markers of the neurofibrillary degeneration.
We have recently reported that the immunoblot detection of two abnormally phosphorylated tau proteins, named Tau 64 and 69, in homogenates of cortical areas from patients with Alzheimer's disease (AD) was systematically associated with the presence of neurofibrillary tangles (NFT) and senile plaques (SP) in these areas. A blind study was performed to confirm that these proteins had a reliable diagnostic value and to study more precisely the correlation between Tau 64 and 69 and the presence of the characteristic lesions of AD. The density of NFT and of SP was evaluated on histological sections of gyrus supramarginalis from 17 patients with graded intellectual status. Immunodetection of Tau 64 and 69 was semiquantitatively evaluated by densitometry (reflectance mode) on immunoblots of homogenates of the same area on the contralateral hemisphere. The statistical analysis of results showed that Tau 64 and 69 were more strongly correlated with NFT than with SP. Moreover, semiquantitative evaluation of Tau 64 and 69 was correlated with the intellectual status (BTS score). Therefore, these pathological forms of tau proteins are reliable markers of the presence of NFT and SP in the neocortex and may be used as a diagnostic tool.


A rapid evoked potential index of cortical adaptation.
Contrast thresholds and acuity limits were measured in 4 observers with the swept visual evoked potential (VEP) technique. In this technique, grating contrast or grating spatial frequency is electronically varied while the subject's evoked response is retrieved in real time (without averaging). Contrast or spatial frequency variation make the stimulus vary in intensity; zero VEP response amplitude indicates the threshold intensity. Large shifts occur in the indicated threshold when stimulus sweep direction is reversed. Thresholds are always relatively elevated when the run begins with the strongest stimulus value. These shifts do not have a technical origin in the delay of the instrument (Nelson et al. 1984b). Here, it is shown that the shifts are due to orientation and spatial frequency selective adaptation, probably of cortical origin. Measureable adaptation is produced by momentary exposure to contrasts as low as 1.25%; nearly maximum adaptation (0.6 log units) is reached with 20% contrast. These findings support the concept of a contrast gain control mechanism in visual cortex, and pose practical problems for visual assessment with the evoked potential.


No evidence of DNA damage by co-exposure to extremely low frequency magnetic fields and aluminum on neuroblastoma cell lines.
Whether exposure to 50-60Hz extremely low frequency magnetic fields (ELF-MF) exerts neurotoxic effects is a debated issue. Analogously, the potential role of Aluminum (Al) in neurodegeneration is a matter of controversial debate. As all living organisms are exposed to ELF-MF and/or Al daily, we found investigating the early effects of co-exposure to ELF-MF and Al in SH-SY5Y and SK-N-BE-2 human neuroblastoma (NB) cells intriguing. SH-SY5Y5 and SK-N-BE-2 cells underwent exposure to 50Hz ELF-MF (0.01, 0.1 or 1mT) or AlCl3 (4 or 40μM) or co-exposure to 50Hz ELF-MF and AlCl3 for 1h continuously or 5h intermittently. The effects of the treatment were evaluated in terms of DNA damage, redox status changes and Hsp70 expression. The DNA damage was assessed by Comet assay; the cellular redox status was investigated by measuring the amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) while the inducible Hsp70 expression was evaluated by western blot analysis and real-time RT-PCR. Neither exposure to ELF-MF or AlCl3 alone induced DNA damage, changes in GSH/GSSG ratio or variations in Hsp70 expression with respect to the controls in both NB cell lines. Similarly, co-exposure to ELF-MF and AlCl3 did not have any synergic toxic effects. The results of this in vitro study, which deals with the effects of co-exposure to 50Hz MF and Aluminum, seem to exclude that short-term exposure to ELF-MF in combination with Al can have harmful effects on human SH-SY5Y and SK-N-BE-2 cells.


Should a lateral chest radiograph be routine in suspected pneumonia?
A study was undertaken on the chest X-rays of 414 children suspected clinically of having pneumonia, to ascertain whether the lateral film provided additional diagnostic information. In only nine cases the lateral film confirmed the diagnostic value of the frontal film and it is suggested that a routine lateral chest film should not be taken for children suspected of having pneumonia.


[Disseminated intravascular coagulation in children under 1 year of age].
In this paper, comparison is made of the clinical with the anatomicopathological diagnosis of DIC. The review of the postmortem studies covered from March 1975 to March 1976 at Hospital de Pediatrïa, C.M.N., and the following were the conclusions: Only in 40 of the cases, the clinical diagnosis of DIC was made. DIC was seen more frequently in the neonatal stage. The anatomicopathological diagnostic criterion is emphasized. Hemorrhages and thromboses predominated in lungs. Paracoagulation tests were not useful.


LEADER surveillance program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from the United States (50 medical centers).
Surveillance for emerging linezolid resistance among commonly occurring Gram-positive pathogens in the United States began with the 2002 ZAAPS program and more recently (2004) expanded as the LEADER program. The 2006 LEADER program processed 5374 strains from 50 medical centers (100 per site) located within the 9 US census regions; species and number tested by broth microdilution (% linezolid susceptible) included Staphylococcus aureus (2913, >99.9), coagulase-negative staphylococci (CoNSs) (808, 98.4), enterococci (547, 97.4), Streptococcus pneumoniae (546, 100.0), viridans group streptococci (189, 100.0), and beta-hemolytic streptococci (371, 100.0). In addition to 1 linezolid-nonsusceptible S. aureus, 3 strains were daptomycin-nonsusceptible, 4 were quinupristin/dalfopristin-intermediate, 2 were vancomycin-intermediate (vancomycin MIC values, 4 mug/mL), and all were methicillin-resistant S. aureus. Among the linezolid-resistant isolates (1 S. aureus, 13 CoNSs, 3 Enterococcus faecalis, and 10 Enterococcus faecium isolates), all but 3 Staphylococcus epidermidis isolates had the G2567T mutation. Overall, 99.55% of the tested 2006 LEADER program isolates remained susceptible to linezolid at current Clinical and Laboratory Standards Institute breakpoints.


Effect of polyamines on synthesis and degradation of guanosine 5'-diphosphate 3'-diphosphate.
The effect of polyamines on the in vitro and in vivo synthesis and degradation on guanosine 5'-diphosphate 3'-diphosphate (ppGpp) has been studied in Escherichia coli. The presence of 2 mM spermidine lowered the optimal Mg2+ concentration for ppGpp formation from 17 mM to 11 mM. The formation of ppGpp in the presence of 2 mM spermidine and 11 mM Mg2+ was about 15% greater than that in the presence of 17 mM Mg2+. At a concentration of less than 11 mM Mg2+, spermidine was found to stimulate ppGpp formation greatly. Putrescine did not cause any effect. When a polyamine-requiring mutant of E. coli (EWH319) was starved for an amino acid by the addition of valine, spermidine stimulated ppGpp formation. The degradation of ppGpp was not influenced significantly by polyamines.


Nardostachys jatamansi protects against liver damage induced by thioacetamide in rats.
Nardostachys jatamansi is a medically important herb of Indian origin used for centuries in Ayurvedic and Unani systems of medicine for the treatment of various ailments. In the present paper, a 50% ethanolic extract of the rhizomes of N. jatamansi is shown to possess hepatoprotective activity. Pretreatment of rats with the extract (800 mg/kg body wt, orally) for three consecutive days significantly ameliorated the liver damage in rats exposed to the hepatotoxic compound thioacetamide. Elevated levels of serum transaminases (aminotransferases) and alkaline phosphatase, observed in thioacetamide alone treated group of animals, were significantly lowered in N. jatamansi pretreated rats. Pretreatment of the animals with the extract also resulted in an increase in survival in rats intoxicated with LD90 dose of the hepatotoxic drug.


Reduced nitric oxide reactivity of a new recombinant human hemoglobin attenuates gastric dysmotility.
The objective of this investigation was to compare the gastric motility effects of two recombinant hemoglobin variants, rHb1.1, and rHb3011, the latter having decreased nitric oxide reactivity via mutagenic alteration. Variants were administered to rats at 750 and 1500 mg/kg, i.v., prior to feeding a meal. The percentage of meal emptied was determined 45 min after feeding. rHb1.1 reduced gastric emptying significantly (48% and 71%), whereas rHb3011 was significant (42%) only at the higher dose (p < 0.05). The results suggest that rHb1.1 inhibits gastric emptying by scavenging NO, and this effect is significantly reduced by rHb3011, which has decreased NO reactivity.


Nutrient dynamics in small mesotrophic fens surrounded by cultivated land : II. N and P accumulation in plant biomass in relation to the release of inorganic N and P in the peat soil.
Release of inorganic N and P in the organic soils of three small quaking fens in The Netherlands was studied by means of in situ incubation of the peat soil in plastic bottles. One of the fens had higher biomass production and lower species richness than the other two. The former fen is located in an area with downward groundwater percolation, whereas the latter fens are situated in an area of upward seepage of groundwater rich in calcium and bicarbonate.Mineralization of N proved to be slow in the low-productive fens, and 6 times faster in the highly productive fen. In the latter fen the amount of N mineralized during a certain period exceeded by far the amount accumulated in that period in the above-ground parts of the vegetation.The release of inorganic P was extremely slow in the two low-productive fens and rapid in the highly productive fen. The release rates were not related to the total P content of the soils. The slow P release in the low-productive fens may be due to the continuous inflow of groundwater rich in Ca, Al and Fe compounds.It can be concluded that the soil is a potentially large source of inorganic N and P in quaking fens. The importance of the soil versus other N and P sources is greater in nutrient-rich fens.


Ultrastructural localization of vanadium in the blood cells of Ascidiacea.
X-ray histospectrographic analysis at the scanning and transmission electron microscope (STEM) are made on the blood cells of Phallusia mamillata Cuvier and Ciona intestinalis, to study the 'direct' intracellular sites of accumulation of vanadium. The results show a clear accumulation of vanadium on the membrane and in the granules of vacuoles of amebocytes, signet ring cell, compartment cell and traces of metal in the 'vanadophores' of vanadocytes.


Results of Radiological and Serological Screenings in Individuals Sharing the Same Living Area as Patients with Hydatid Cyst in Afghanistan's State Hospital
To determine the results of radiological and serological screenings in individuals who shared the same living space as patients with hydatid cyst in a State Hospital of Afghanistan. Patients presenting with hydatid cyst to a public hospital in Afghanistan were included in this study. Full sampling method was used. Also, the relatives of the patients were called to the hospital and investigated for the presence of hydatid cyst antibodies through direct chest X-ray, upper abdominal ultrasonography and ELISA. During the study period, a total of 214 patients, including 102 male and 112 female, underwent radiological and serological screenings. While cysts were radiologically detected in the liver, lung and spleen in 8, 2 and 1 patient, respectively, the serology was positive in 22 patients. As a result of the study, it was concluded that the patients who shared the same environment as the patients who were diagnosed with hydatid cyst in an endemic region for cyst hydatid disease.


Visualization and Quantification of Nasal and Olfactory Deposition in a Sectional Adult Nasal Airway Cast.
To compare drug deposition in the nose and olfactory region with different nasal devices and administration techniques. A Sar-Gel based colorimetry method will be developed to quantify local deposition rates. A sectional nasal airway cast was developed based on an MRI-based nasal airway model to visualize deposition patterns and measure regional dosages. Four nasal spray pumps and four nebulizers were tested with both standard and point-release administration techniques. Delivered dosages were measured using a high-precision scale. The colorimetry correlation for deposited mass was developed via image processing in Matlab and its performance was evaluated through comparison to experimental measurements. Results show that the majority of nasal spray droplets deposited in the anterior nose while only a small fraction (less than 4.6%) reached the olfactory region. For all nebulizers considered, more droplets went beyond the nasal valve, leading to distinct deposition patterns as a function of both the nebulizer type (droplet size and initial speed) and inhalation flow rate. With the point-release administration, up to 9.0% (±1.9%) of administered drugs were delivered to the olfactory region and 15.7 (±2.4%) to the upper nose using Pari Sinus. Standard nasal devices are inadequate to deliver clinically significant olfactory dosages without excess drug losses in other nasal epitheliums. The Sar-Gel based colorimetry method appears to provide a simple and practical approach to visualize and quantify regional deposition.


Identification of SARS-CoV-2 biomarkers in saliva by transcriptomic and proteomics analysis.
The detection of SARS-CoV-2 biomarkers by real time PCR (rRT-PCR) has shown that the sensitivity of the test is negatively affected by low viral loads and the severity of the disease. This limitation can be overcome by the use of more sensitive approaches such as mass spectrometry (MS), which has not been explored for the detection of SARS-CoV-2 proteins in saliva. Thus, this study aimed at assessing the translational applicability of mass spectrometry-based proteomics approaches to identify viral proteins in saliva from people diagnosed with COVID-19 within fourteen days after the initial diagnosis, and to compare its performance with rRT-PCR. After ethics approval, saliva samples were self-collected by 42 COVID-19 positive and 16 healthy individuals. Samples from people positive for COVID-19 were collected on average on the sixth day (± 4 days) after initial diagnosis. Viable viral particles in saliva were heat-inactivated followed by the extraction of total proteins and viral RNA. Proteins were digested and then subjected to tandem MS analysis (LC-QTOF-MS/MS) using a data-dependent MS/MS acquisition qualitative shotgun proteomics approach. The acquired spectra were queried against a combined SARS-CoV-2 and human database. The qualitative detection of SARS-CoV-2 specific RNA was done by rRT-PCR. SARS-CoV-2 proteins were identified in all COVID-19 samples (100%), while viral RNA was detected in only 24 out of 42 COVID-19 samples (57.1%). Seven out of 18 SARS-CoV-2 proteins were identified in saliva from COVID-19 positive individuals, from which the most frequent were replicase polyproteins 1ab (100%) and 1a (91.3%), and nucleocapsid (45.2%). Neither viral proteins nor RNA were detected in healthy individuals. Our mass spectrometry approach appears to be more sensitive than rRT-PCR for the detection of SARS-CoV-2 biomarkers in saliva collected from COVID-19 positive individuals up to 14 days after the initial diagnostic test. Based on the novel data presented here, our MS technology can be used as an effective diagnostic test of COVID-19 for initial diagnosis or follow-up of symptomatic cases, especially in patients with reduced viral load.


Incidence rates of pelvic inflammatory disease diagnoses among Army and Navy recruits potential impacts of Chlamydia screening policies.
U.S. Navy policy requires Chlamydia trachomatis screening of all women upon entry to recruit training in conjunction with an educational session, and yearly screening thereafter until age 25. Army policy directs only annual screening of asymptomatic women aged <25. Hence, screening of Army recruits may not occur for up to 12 months following accession. Using routinely collected surveillance data, the rates of outpatient pelvic inflammatory disease (PID) following accession into the Army or Navy were compared to assess the potential implications of these policies. The population at risk comprised active-component women aged <25 who accessioned to either the U.S. Army or Navy between January 1, 2001, and December 31, 2005. Subjects were followed up to 60 months from accession, either until a first outpatient PID diagnosis occurred or they departed from military service. Data were collected from 2001 to 2006 and analyzed in 2007. Multiple Poisson regression was used to assess the effects of potentially important covariates. Time-to-event analysis was employed to characterize risk over time. There were 1276 and 546 incident outpatient diagnoses of PID among 58,088 Army and 33,046 Navy accessions during 93,918 and 65,863 person-years of follow-up, respectively. The crude incident rate was 64% higher in the Army (13.6/1000 person-years) than the Navy (8.3/1000 person-years). Risk for the Army increased soon after accession, followed by a decline, while risk for the Navy remained comparatively uniform. PID rates were higher in the Army than Navy during the first years of active service. A comprehensive study to elucidate the source of this observed difference is warranted.


TGF-β Induces Up-Regulation of Chondroitin Sulfate Synthase 1 (CHSY1) in Nucleus Pulposus Cells Through MAPK Signaling.
Chondroitin sulfate synthase 1 (CHSY1) is a glycosyltransferases involved in the biosynthesis of chondroitin and dermatan sulfate glycosaminoglycan (GAG). TGF-β can stimulate sulfated GAG production in nucleus pulposus cells; however, the underlying mechanisms are poorly understood. CHSY1 expression was examined in rat nucleus pulposus treated with TGF-β using real-time PCR and Western blot analysis. Lentiviral knockdown was performed to determine the downstream effectors of TGF-β and to measure the effect of c-Jun and Sp1 on TGF-β mediated CHSY1 promoter activity and CHSY1 expression. TGF-β increased CHSY1 expression and promoter activity in the nucleus pulposus partially through activation of canonical Smad signaling pathway. Knockdown of c-Jun and Sp1 decreased CHSY1 promoter activity, CHSY1 expression and sGAG accumulation induced by TGF-β. Furthermore, we found that TGF-β-induced expression of CHSY1 was mediated through the activation of MAPK signaling. Moreover, we showed that silencing CHSY1 decreased sGAG accumulation in nucleus pulposus cells induced by TGF-β. Our results suggest that TGF-β induced CHSY1 expression in the nucleus pulposus through the activation of MAPK signaling.


Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis.
Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients' perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.


The occurrence of ectopic pregnancy with and without clomiphene citrate use in assisted and nonassisted reproductive technology.
An eleven-year review of treatment records of patients who became pregnant as a result of infertility treatment (n = 3692) was conducted. All records were examined to determine whether clomiphene citrate (CC) was used in the cycle of conception and whether or not an ectopic pregnancy occurred. Data were additionally analyzed for the incidence of ectopic pregnancy with and without assisted reproductive technology (ART). The incidence of ectopic pregnancy was similar between CC (3.4%) and non-CC (3.4%) treatment groups receiving non-ART treatment. For non-ART treatments, tubal disease and severe endometriosis resulted in an increase in ectopic pregnancies independent of CC use. The incidence of ectopic pregnancy in patients receiving CC + human menopausal gonadotropin (hMG) for in vitro fertilization (5.4%) and gamete intrafallopian transfer (3.1%) was similar compared to ART treatments with hMG alone. The incidence of ectopic pregnancy was more closely associated with infertility diagnosis rather than CC use.


[Challenges in building a surgical obesity center].
It is estimated that approximately 1 million adults in Germany suffer from grade III obesity. The aim of this article is to describe the challenges faced when constructing an operative obesity center. The inflow of patients as well as personnel and infrastructure of the interdisciplinary Diabetes and Obesity Center in Heidelberg were analyzed. The distribution of continuous data was described by mean values and standard deviation and analyzed using variance analysis. The interdisciplinary Diabetes and Obesity Center in Heidelberg was founded in 2006 and offers conservative therapeutic treatment and all currently available operative procedures. For every operative intervention carried out an average of 1.7 expert reports and 0.3 counter expertises were necessary. The time period from the initial presentation of patients in the department of surgery to an operation was on average 12.8 months (standard deviation SD ± 4.5 months). The 47 patients for whom remuneration for treatment was initially refused had an average body mass index (BMI) of 49.2 kg/m(2) and of these 39 had at least the necessity for treatment of a comorbidity. Of the 45 patients for whom the reason for the refusal of treatment costs was given as a lack of conservative treatment, 30 had undertaken a medically supervised attempt at losing weight over at least 6 months. Additionally, 19 of these patients could document participation in a course at a rehabilitation center, a Xenical® or Reduktil® therapy or had undertaken the Optifast® program. For the 20 patients who supposedly lacked a psychosomatic evaluation, an adequate psychosomatic evaluation was carried out in all cases. The establishment of an operative obesity center can last for several years. A essential prerequisite for success seems to be the constructive and targeted cooperation with the health insurance companies.


Tension pneumocephalus secondary to non-invasive mechanical ventilation in a patient with severe traumatic brain injury.
The presence of air inside intracranial cavity is a rare entity known as pneumocephalus and in most cases doesńt present any clinical repercussion except in case of elevated intracranial pressure that can lead to a decreasing level of consciousness, coma and even death. We present a rare case of a young male, without medical precedents of interest, hospitalized in an intensive care unit for vigilance after a traffic accident with asymptomatic crane encephalic trauma and cranial computerized tomography without meaningful findings. During the intensive care unit stay positive pressure is applied in airway with non-invasive mechanical ventilation that produces air entrance in cranial cavity (pneumocephalus) causing neurological deterioration and necessity of urgent surgery.


Changes in the length of the human biceps brachii muscle during elbow movements.
1. Needles inserted into the biceps move with the muscle as the elbow flexes or extends. Pairs of needles were used to indicate changes in length of the muscle fibres. 2. During low-frequency flexion-extension movements the biceps lengthened as the joint extended. 3. When, however, joint movements at greater than 2.2 Hz were maintained by external electrical stimulation of triceps and the long head of biceps, or of biceps alone, the biceps lengthened and shortened in antiphase to the joint movement. The elastic properties of the biceps tendons then combined with the mass of the forearm as a spring-mass system whose natural frequency was about 2.2 Hz. 4. No such phase reversal appeared during voluntary elbow movements at frequencies up to 5 Hz. It was concluded that the combined tendons of biceps, brachialis and brachioradialis made a much less compliant muscle-to-bone coupling. 5. The results are discussed in relation to possible tremor mechanisms.


Reading and Study Habits of Medical Students on Clerkships and Performance Outcomes: a Multi-institutional Study.
To describe medical students' reading habits and resources used during clinical clerkships, and to assess whether these are associated with performance outcomes. Authors administered a cross-sectional survey to medical students at 3 schools midway through the clerkship year. Closed and open-ended questions focused on resources used to read and learn during the most recent clerkship, time spent and purpose for using these resources, influencers on study habits, and barriers. A multiple regression model was used to predict performance outcomes. Overall response rate was 53% (158/293). Students spent most of their time studying for clerkship exams and rated question banks and board review books as most useful for exam preparation. Sixty-seven percent used textbooks (including pocket-size). For patient care, online databases and pocket-sized textbooks were rated most useful. The main barrier to reading was time. Eighty percent of students ranked classmates/senior students as most influential regarding recommended resources. Hours spent reading for exams was the only significant predictor of USMLE Step 2 scores related to study habits. The predominant advice offered to future students was to read. These findings can help inform students and educational leadership about resources students use, how they use them, and links to performance outcomes, in an effort to guide them on maximizing learning on busy clerkships. With peers being most influential, it is important not only to provide time to help students build strong reading and study habits early, but also to guide them towards reliable resources, so they will recommend useful information to others.


Oxidative DNA damage induced by photodegradation products of 3(')-azido-3(')-deoxythymidine.
3(')-Azido-3(')-deoxythymidine (AZT) is carcinogenic to experimental animals and can cause the formation of 8-oxo-7,8-dihydro-2(')-deoxyguanosine (8-oxodG) in humans and animals. To clarify the mechanism of carcinogenesis by AZT, we investigated DNA damage induced by its photodegradation products, using 32P-5(')-end-labeled DNA fragments obtained from human genes. Following exposure to UVB, AZT induced DNA damage in the presence of Cu(II). Catalase inhibited DNA damage, indicating the involvement of H(2)O(2). UVB-exposed AZT plus Cu(II) induced 8-oxodG formation in a dose-dependent manner. Mass spectrum of UVB-exposed AZT demonstrated the generation of a hydroxylamine derivative. The colorimetric determination suggested that AZT was converted into the hydroxylamine derivative depending on UVB doses. UVB-exposed AZT induced double base damage at the 5(')-ACG-3(') sequence, complementary to a hot spot of the p53 gene. The basic compound, hydroxylamine, showed similar site specificity. The hydroxylamine derivative produced by photodegradation and/or possible metabolism of AZT induces oxidative DNA damage, which may participate in carcinogenesis.


Early postnatal development of monkey subthalamic nucleus: a light and electron microscopic study.
The subthalamic nuclei of 9 rhesus monkeys, ranging in age from newborn to 17 weeks, were examined at the light and/or electron microscopic levels, using computer assisted quantitative methods. The volume of the structure does not change significantly over the period of study. The mean cross-sectional area of neuronal somata, however, decreases by 33%, and most markedly during the first month. This is paralleled by a similar change in the mean area of cell nuclei but the perikaryon/nucleus ratio increases steadily after the first week. There is an overall decline in total cell numbers from newborn to 17 weeks. Ultrastructural features include dendritic growth cones in the neonatal monkey, and signs of axonal degeneration during the entire period. In addition to conventional axosomatic and axodendritic synapses, there are also synaptic junctions between vesicle-containing profiles which are seen only after the first month. The distributions of plaque diameters were reconstructed by the Coupland stereologic method from linear measurements of synaptic profiles and used to calculate synaptic densities and estimate the total number of synapses. This number is stable during the first postnatal month, declines markedly in the second month, and to a lesser degree thereafter, reaching a value of 55% of that at birth by 16 weeks. Findings indicate the occurrence of substantial changes within the subthalamic nucleus during the first 4 postnatal months, the most prominent of which is a marked synapse elimination.


Quinolones as gonadotropin releasing hormone (GnRH) antagonists: simultaneous optimization of the C(3)-aryl and C(6)-substituents.
A series of 3-arylquinolones was prepared and evaluated for their ability to act as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl substituent (23h) was found to be optimal.


Nonischemic dilated cardiomyopathy: results of noninvasive and invasive evaluation in 310 patients and clinical significance of bundle branch block.
The survival of patients with idiopathic dilated cardiomyopathy (IDCM) at III and IV stages of New York Heart Association (NYHA) is decreased in those with a bundle branch block (BBB) compared to those without BBB. Less is known on the prognosis of patients at earlier stages of NYHA and who had a left BBB (LBBB) or right BBB (RBBB). We sought to evaluate the prevalence and the clinical significance of LBBB or RBBB in patients with IDCM and classes I and II of NYHA. Clinical data, noninvasive, and invasive studies were consecutively collected in 310 patients, with IDCM, followed up to 4.8+/-3.7 years. Seventy-six patients (25%) had LBBB, 21 (7%) had RBBB, and 212 had no BBB. Patients with BBB were older than other patients (P < 0.009). Left ventricular ejection fraction (LVEF) was lower in LBBB than in RBBB and other patients (P < 0.05). Syncope was more frequent in BBB than in absence (P < 0.05). Incidence of spontaneous ventricular tachycardia (VT) and atrial fibrillation, VT induction, total cardiac events, and sudden death were similar in the presence or absence of BBB. Deaths by heart failure and heart transplantations tended to be more frequent in BBB than in absence. LBBB was present in 25% of patients with IDCM; RBBB was rare. Patients with BBB were older and had more frequent syncope than patients without BBB; LVEF was lower in LBBB than in RBBB or in absence of BBB. BBB did not increase the risk of spontaneous VT, VT induction, or sudden death, and tended to increase deaths by heart failure and the indications of heart transplantation.


Evaluation of pure tone and speech discrimination changes in Usher's syndrome.
Twenty-three adult patients with type 2 Usher's syndrome were evaluated for changes in pure tone average (PTA), discrete frequency thresholds, and speech discrimination scores. These patients were evaluated over a period of 5 years on the average (range, 2 to 9 years). Analyses of ear data showed a less than 10-dB change on PTA and discrete frequency thresholds for most ears. Of the ears that showed a threshold change greater than or equal to 10 dB, statistical significance was reached only at 4,000 Hz (p less than .01), where 11 ears representing ten patients dropped 10 to 15 dB. Speech discrimination data showed a greater than or equal to 16% change in score for 18 ears (12 patients). Sixteen of those ears (ten patients) had a 16% to 52% decrease in score (p less than .01), and the remaining two ears (two patients) showed a 20% and 30% improvement in score. These findings document little or no change in pure tone sensitivity for type 2 Usher's syndrome patients, but demonstrate the importance of monitoring their speech discrimination performance.


Determinants of birth asphyxia among newborn live births in public hospitals of Gamo and Gofa zones, Southern Ethiopia.
Birth asphyxia is the inability of a newborn to start and conserve breathing immediately after birth. Globally, 2.5 million infants die within their first month of life every year, contributing nearly 47% of all deaths of children. It is the third cause of neonatal deaths next to infections and preterm birth. Ethiopia is one of the countries with the highest neonatal mortality and high burden of birth asphyxia in the world. The state of birth asphyxia is about 22.52% in Ethiopia, with incidence of 18.0% in East Africa Neonatal mortality incidence ratio was 9.6 deaths per 1000 live births among which 13.5% of neonatal mortality cases were due to birth asphyxia in southern Ethiopia. The effect of birth asphyxia is not only limited to common clinical problems and death; it also has a socio-economic impact on the families. Therefore, this study is aimed to identify determinants of birth asphyxia among newborn live births in public hospitals Southern Ethiopia. An Institution based unmatched case-control study was conducted among newborn live births in public hospitals of Gamo & Gofa zones, with a total sample size of 356 (89 cases and 267 controls, 1:3 case to control ratio) from March 18 to June 18, 2021, after obtaining ethical clearance from Arba Minch University. Cases were selected consecutively and controls were selected by systematic random sampling method. Data were collected using an adapted pretested semi-structured questionnaire through face-to-face interviews and record reviews using an extraction checklist for intrapartum & neonatal-related information. The collected data were entered into Epi data version 4.4 and exported to STATA version 14 for analysis. Finally, bi-variable and multivariable logistic regression analyses were performed to identify determinants of birth asphyxia. Statistical significance was declared at p-value ≤ 0.05 along with corresponding 95% CI of AOR used to declare statistical significance. Anemia during pregnancy [AOR = 3.87, 95% CI (1.06- 14.09)], breech presentation [AOR = 3.56, 95% CI (1.19-10.65)], meconium stained amniotic fluid [AOR = 6.16, 95% CI (1.95-19.46)], cord prolapse [AOR = 4.69, 95%CI (1.04-21.05)], intrapartum fetal distress [AOR = 9.83, 95% CI (3.82-25.25)] and instrumental delivery [AOR = 5.91, 95% CI (1.51-23.07)] were significantly associated with birth asphyxia. The study revealed that anemia during pregnancy, breech presentation, meconium-stained amniotic fluid, cord prolapse, intrapartum fetal distress, and instrumental delivery were identified as determinants of birth asphyxia. Therefore, health professional and health institutions should give emphasis on care of mother and the newborn in actively detecting and managing asphyxia.


No evidence of enhanced satiety following whey protein- or sucrose-enriched water beverages: a dose response trial in overweight women.
To compare the effect of low-dose whey protein-enriched and sucrose-enriched water beverages on postprandial satiety and energy intake. Sixty overweight and obese women were given water-based protein and carbohydrate (CHO) beverages or placebo on six different occasions in a double-blind, randomised cross-over study. The beverages were 2 (178 kJ) and 4% (348 kJ) protein-enriched water (Clear Protein8855), 2 (157 kJ), 4 (314 kJ) and 10% (785 kJ) sucrose-enriched water, and a sweetened water control. Beverages were matched for volume, colour, flavour and sweetness. A standardised evening meal was provided before each study day and a standardised breakfast upon arrival at the clinic at 0900 hours. The beverage preload was given midmorning at 1100 hours, and an ad libitum outcome lunch meal at 1300 hours. Subjective appetitive responses were recorded through the day until 1500 hours using visual analogue scales. Fifty-five participants completed all six beverage conditions. Neither protein nor sucrose preloads decreased any of hunger, fullness, thoughts of food or satisfaction when compared with the sweetened water control beverage (all, P>0.05). There was also no significant effect on ad libitum energy or macronutrient intake at the outcome meal (P>0.05), with no compensation for the energy consumed within the preload beverages. There was no evidence of increased postprandial satiety or compensation for energy content at an outcome lunch meal when a water beverage was supplemented with up to 4% (w/w) whey protein or 10% (w/w) sucrose, in a group of overweight but unrestrained young and middle-aged women.


The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients.
The purposes of this study were to analyze the effect of trans-sutural distraction osteogenesis (TSDO) on nasal bone, nasal septum, and nasal airway in the treatment of midfacial hypoplasia. A total of 29 growing patients with midfacial hypoplasia who underwent TSDO by a single surgeon were enrolled. The 3-dimensional measurement of nasal bone and nasal septum changes was performed using computed tomography (CT) images obtained preoperatively (T0) and postoperatively (T1). One patient was selected to establish 3-dimensional finite element models to simulate the characteristics of nasal airflow field before and after traction. After traction, the nasal bone moved forward significantly ( P <0.01). The septal deviation angle was lower than that before traction (14.43±4.70 versus 16.86 ±4.59 degrees) ( P <0.01). The length of the anterior and posterior margin of the vomer increased by 21.4% ( P <0.01) and 27.6% ( P <0.01), respectively, after TSDO. The length of the posterior margin of the perpendicular plate of ethmoid increased ( P <0.05). The length of the posterior inferior and the posterior superior margin of the nasal septum cartilage increased ( P <0.01) after traction. The cross-sectional area of nasal airway on the deviated side of nasal septum increased by 23.0% after traction ( P <0.05). The analysis of nasal airflow field showed that the pressure and velocity of nasal airflow and the nasal resistance decreased. In conclusion, TSDO can promote the growth of the midface, especially nasal septum, and increase the nasal space. Furthermore, TSDO is conductive to improve nasal septum deviation and decrease nasal airway resistance.


Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers.
The serine-glycine-one-carbon (SGOC) metabolic pathway is critical for DNA methylation, histone methylation, and redox homeostasis, in addition to protein, lipid, and nucleotide biosynthesis. The SGOC pathway is a crucial metabolic network in tumorigenesis, wherein the outputs are required for cell survival and proliferation and are particularly likely to be co-opted by aggressive cancers. SGOC metabolism provides an integration point in cell metabolism and is of crucial clinical significance. The mechanism of how this network is regulated is the key to understanding tumor heterogeneity and overcoming the potential mechanism of tumor recurrence. Herein, we review the role of SGOC metabolism in cancer by focusing on key enzymes with tumor-promoting functions and important products with physiological significance in tumorigenesis. In addition, we introduce the ways in which cancer cells acquire and use one-carbon unit, and discuss the recently clarified role of SGOC metabolic enzymes in tumorigenesis and development, as well as their relationship with cancer immunotherapy and ferroptosis. The targeting of SGOC metabolism may be a potential therapeutic strategy to improve clinical outcomes in cancers.


Apgar Scores Are Associated with Attention-Deficit/Hyperactivity Disorder Symptom Severity.
Adverse events during pregnancy and delivery have been linked to attention-deficit/hyperactivity disorder (ADHD). Previous studies have investigated Apgar scores, which assess the physical condition of newborns, in relation to the risk of developing ADHD. We propose to go one step further and examine if Apgar scores are associated with ADHD symptom severity in children already diagnosed with ADHD. ADHD symptoms severity, while off medication, was compared in 2 groups of children with ADHD: those with low (≤6, n = 52) and those with higher (≥7, n = 400) Apgar scores sequentially recruited from the ADHD clinic. Children with low Apgar at 1 minute after birth had more severe symptoms as assessed by the externalizing scale of the Child Behaviour Checklist, the Conners' Global Index for Parents, and the DSM-IV hyperactivity symptoms count (P = 0.02, <0.01, <0.01, respectively). Low 1-minute Apgar scores are associated with a significant increase in ADHD symptom severity. These findings underline the importance of appropriate pregnancy and perinatal care.


YiQiFuMai lyophilized injection attenuates cerebral ischemic injury with inhibition of neuronal autophagy through intervention in the NMMHC IIA-actin-ATG9A interaction.
YiQiFuMai lyophilized injection (YQFM) is derived from a traditional Chinese medicine prescription termed Shengmai San.YQFM is clinically applied to the treatment of cardiovascular and cerebrovascular diseases. It has been found that critical components of YQFM affect non-muscle myosin heavy chain IIA (NMMHC IIA), but its regulation in the excessive autophagy and the underlying mechanism has yet to be clarified. To evaluate whether YQFM has neuroprotective effects on cerebral ischemia/reperfusion-induced injury by inhibiting NMMHC IIA-actin-ATG9A interaction for autophagosome formation. The neuroprotective effects of YQFM were investigated in vivo in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) (n = 6) by detecting neurological deficits, infarct volume, and histopathological changes. The NMMHC IIA-actin-ATG9A interaction was determined using immunofluorescence co-localization, co-immunoprecipitation, and proximity ligation assay. Rat pheochromocytoma (PC12) cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic neurons in in vitro experiments. In MCAO/R model mice, YQFM (1.342 g/kg) attenuated brain ischemia/reperfusion-induced injury by regulating NMMHC IIA-actin-mediated ATG9A trafficking. YQFM (400 μg/ml) also exerted similar effects on OGD/R-induced PC12 cells. Furthermore, RNAi of NMMHC IIA weakened the NMMHC IIA-F-actin-dependent ATG9A trafficking and, therefore, attenuated the neuroprotective activities of YQFM in vitro. These findings demonstrated that YQFM exerted neuroprotective effects by regulating the NMMHC IIA-actin-ATG9A interaction for autophagosome formation. This evidence sheds new light on the potential mechanism of YQFM in the treatment of cerebral ischemia/reperfusion.


Mixotrophic Microalgae Biofilm: A Novel Algae Cultivation Strategy for Improved Productivity and Cost-efficiency of Biofuel Feedstock Production.
In this work, we studied a novel algae cultivation strategy, mixotrophic microalgae biofilm, to improve the productivity and cost-efficiency of algal biofuel production. In contrast to previous methods, this improved approach can achieve high productivity at low cost by harnessing the benefits of mixotrophic growth's high efficiency, i.e., capable of subsisting on inorganic and organic carbons thus unaffected by limited light, and microalgae biofilm's low harvesting cost. Our results, as one of the first studies of this type, proved that microalgae biofilms under mixotrophic condition exhibited significantly higher productivity and quality of biofuel feedstock: 2-3 times higher of biomass yield, 2-10 times higher of lipid accumulation, and 40-60% lower of ash content when compared to microalgae biofilms under autotrophic condition. In addition, we investigated the impact of cell-surface properties (hydrophobicity and roughness) on the growth activities of microalgae biofilms and found that the productivity of mixotrophic biofilms was significantly correlated with the surface hydrophobicity. Finally, our work demonstrated the applicability of integrating this novel cultivation method with wastewater for maximum efficiency. This study opens a new possibility to solve the long-lasting challenges of algal biofuel feedstock production, i.e., low productivity and high cost of algal cultivation.


[Encountering the person in his environment--approaches to psychosocial management].
Is it necessary to understand your vis a vis or is it enough to meet, to get in touch? Awareness of the different perception of reality is important. INTERINDIVIDUELL: Defined as basic requirements for getting in touch, mutual modelling and interchange were "Knowing your own world", "Being curious about the world of the other", candour and tolerance. Time makes the essential framework. Are the interindividuell parameters also practicable for groups/organizations? In the psychosocial context the subjective perception of the world is cause and cure at the same time. The basic requirements enable people, by getting in touch, to reorganize themselves.


Comparison of 2 myocardial velocity gradient assessment methods during dobutamine infusion with Doppler myocardial imaging.
Myocardial velocity gradient (MVG) has been shown to be the best quantitative parameter for the detection of ischemic myocardium during dobutamine infusion with the use of Doppler myocardial imaging. MVG has been previously assessed by velocity measurements across the thickness of the myocardium at the time of visually selected maximal color brightness (thickness-velocity plot method). We hypothesized that MVG could be assessed by velocity measurements throughout the cardiac cycle in the subendocardium parallel to the endocardial boundary to the left ventricular cavity and in the subepicardium parallel to the epicardial boundary (time-velocity plot method). This study was designed to compare MVG obtained from the thickness-velocity plot method and from the time-velocity plot method in quantifying dobutamine-induced changes in myocardial wall motion in 8 phases of the cardiac cycle on color M-mode Doppler myocardial imaging recordings of the left ventricular posterior wall performed in 8 conscious dogs at baseline and at steady state during dobutamine infusion (10 microg/kg per minute). For both methods, MVG was considered present if its mean value was significantly different from zero and if endocardial and epicardial velocities were significantly different. There was close agreement between the 2 methods. MVG was present during the preejection period, systole, rapid ventricular filling, and atrial contraction. Dobutamine induced a significant increase in MVG during the preejection period (from 2.64 +/- 0.83 to 4.05 +/- 0.81 seconds-1 ), systole (from 2.14 +/- 0.59 to 6.08 +/- 2.20 seconds-1 in early systole, from 1.90 +/- 1.06 to 5.31 +/- 2.95 seconds-1 in mid systole, from 1.37 +/- 0.57 to 2.44 +/- 0.53 seconds-1 in end systole), and rapid ventricular filling (from 3.06 +/- 1.12 to 7.82 +/- 2.58 seconds-1 ), related to a greater rise in endocardial than in epicardial velocities. The time-velocity plot method showed that ejection and diastole were 11% and 28% decreased during dobutamine infusion, respectively, as heart rate was 31% increased. Thus according to our quantitative criteria, both MVG assessment procedures enabled objective interpretation of dobutamine effects on left ventricular wall motion. In addition, the time-velocity plot method provided automatic detection of peak velocity, timing, and duration of wall velocity changes over time.


Early effects of muscle atrophy on shoulder joint development in infants with unilateral birth brachial plexus injury.
Shoulder deformities in children with a birth brachial plexus injury (BBPI) are caused by muscle imbalances; however, the underlying mechanisms are unclear. The aim of this study was to assess the early interactions between shoulder muscles and shoulder joint development. In a retrospective magnetic resonance imaging (MRI) study of 36 infants (21 males, 15 females) younger than 12 months (mean 4.8 mo) with unilateral BBPI, volumes and thicknesses of standardized segments of the infraspinatus, subscapularis, and deltoid muscles were measured in both shoulders and expressed as ratios of pathological/unaffected side. The relation between muscle ratios and humeral head subluxation, passive external rotation, glenoid version, and deformity was analysed. Compared with the unaffected side, the muscles of the affected side were of significantly smaller volume and thickness. The subscapularis was the most severely affected muscle, its volume being only 64% (SD 21%) and its thickness only 79% (SD 23%) of the corresponding values on the unaffected side (p < 0.001). Severe subluxation was predicted by the combination of low infraspinatus and subscapularis volume ratios (r(2) = 0.223; p = 0.014), but not by muscle thickness ratios. Subluxation was related to passive external rotation (p < 0.05), glenoid version (p < 0.01), and deformity (p < 0.01). In infants with BBPI, muscle size is decreased during in the first months of life by both atrophy and, possibly, by a reduction in the number of sarcomeres in series. These effects are strongly related to shoulder joint subluxation.


Negative effects of phosphorus addition outweigh effects of arbuscular mycorrhizal fungi and nitrogen addition on grassland temporal stability in the eastern Eurasian desert steppe.
The temporal stability of grassland plant communities is substantially affected by soil nutrient enrichment. However, the potential main and interactive effects of arbuscular mycorrhizal fungi (AMF) and soil nitrogen (N) and phosphorus (P) enrichment on the stability of plant productivity have not yet been clarified. We combined a three-year in situ field experiment to assess the impacts of soil fertilization and AMF on the stability of plant productivity. P addition decreased the stability of plant productivity by increasing the standard deviation relative to the mean of plant productivity. However, compared to species richness, the stability of C3 grasses and other functional groups asynchrony were the most important drivers changing the stability of plant productivity. The negative impacts of P addition overrode the impacts of AMF on the stability of plant productivity. Overall, our study suggests the importance of soil nutrient availability over AMF in terms of shaping the stability of plant productivity. Our results also suggest that three-year anthropogenic soil nutrient enrichment could reduce the stability of plant communities in grassland regardless of AMF in the P-limited grassland ecosystem.


The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan.
In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016-2019) and compared the results with our previous survey (2011-2015). The authors also surveyed reproductive specialists' awareness of the guidelines and implementation problems. The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011-2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists' interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.


Severe pulmonary hemorrhage following lymphography.
The hemoptysis which occurs following lymphography typically consists of one or more episodes of blood-tinged sputum, and generally requires no treatment. In contradistinction to this "mild" form of hemoptysis, the current report describes a case of hemoptysis following lymphography--hemoptysis so severe as to require multiple transfusions. Time course and possible etiologic factors are discussed.