A neurophysiological investigation of anticipation to pain in Parkinson's disease.
Chronic pain is common in people with Parkinson's disease and is often considered to be caused by the motor impairments associated with the disease. Altered top-down processing of pain characterises several chronic pain conditions and occurs when the cortex modifies nociceptive processing in the brain and spinal cord. This contrasts with bottom-up modulation of pain whereby nociceptive processing is modified on its way up to the brain. Although several studies have demonstrated altered bottom-up pain processing in Parkinson's, the contribution of enhanced anticipation to pain and atypical top-down processing of pain has not been fully explored. During the anticipation to noxious stimuli, EEG source localisation reported an increased activation in the midcingulate cortex and supplementary motor area in the Parkinson's disease group compared to the healthy control group during mid [-1,500 -1,000]-and late anticipation [-500 0], indicating enhanced cortical activity before noxious stimulation. The Parkinson's disease group was also more sensitive to the laser and required a lower voltage level to induce pain. This study provides evidence supporting the hypothesis that enhanced top-down processing of pain may contribute to the development of chronic pain in Parkinson's. Additional research to establish whether the altered anticipatory response is unique to noxious stimuli is required as no control stimulus was used within the current study. With further research to confirm these findings, our results inform a scientific rationale for novel treatment strategies of pain in Parkinson's disease, including mindfulness, cognitive therapies and other approaches targeted at improving top-down processing of pain.


Effects of chronic ethanol consumption on benzo(a)pyrene metabolism and glutathione S-transferase activities in Syrian golden hamster cheek pouch and liver.
The metabolism of benzo(a)pyrene (BaP) by hepatic or cheek pouch epithelium microsomes obtained from Syrian golden hamsters which had been consuming an ethanol-containing liquid diet for 4 wk and from pair-fed controls was measured. Glutathione S-transferase activity with 1-chloro-2,4-dinitrobenzene or (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene as substrates was measured in cytosol obtained from the liver or cheek pouch epithelium of the same animals. Cytosolic hepatic glutathione levels were measured in both ethanol-consuming and control animals. The metabolism of BaP to 4,5-dihydro-4,5-dihydroxybenzo(a)pyrene (BaP-4,5-diol), 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BaP-7,8-diol), 9-hydroxybenzo(a)pyrene (9-OH-BaP), and 3-hydroxybenzo(a)pyrene (3-OH-BaP) by hepatic microsomes from ethanol-consuming hamsters was significantly reduced (40-52%) (P less than 0.05) compared to control microsomes. However, a 2-fold increase (P less than 0.05) in the metabolism of BaP to BaP-7,8-diol and 9,10-dihydro-9,10-dihydroxybenzo(a)pyrene was measured with microsomes from the cheek pouch epithelium of ethanol-consuming animals. There was no significant change in the production of BaP-4,5-diol, 9-OH-BaP, or 3-OH-BaP by cheek pouch epithelium microsomes of ethanol-consuming hamsters compared to controls. No difference in glutathione S-transferase activity of hepatic or cheek pouch epithelium cytosol between control and ethanol-consuming hamsters towards 1-chloro-2,4-dinitrobenzene or (+/-)-r-7,t-8-dihydroxy-t-9,10- epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was observed. Hepatic glutathione content was significantly (P less than 0.05) decreased after 2 wk (23%) and 4 wk (33%) of ethanol consumption. The results suggest a mechanism by which ethanol might enhance BaP tumorigenesis in the hamster cheek pouch.


SL2: an interactive webtool for modeling of missing segments in proteins.
SuperLooper2 (SL2) (http://proteinformatics.charite.de/sl2) is the updated version of our previous web-server SuperLooper, a fragment based tool for the prediction and interactive placement of loop structures into globular and helical membrane proteins. In comparison to our previous version, SL2 benefits from both a considerably enlarged database of fragments derived from high-resolution 3D protein structures of globular and helical membrane proteins, and the integration of a new protein viewer. The database, now with double the content, significantly improved the coverage of fragment conformations and prediction quality. The employment of the NGL viewer for visualization of the protein under investigation and interactive selection of appropriate loops makes SL2 independent of third-party plug-ins and additional installations.


Visual cortical gamma-band activity during free viewing of natural images.
Gamma-band activity in visual cortex has been implicated in several cognitive operations, like perceptual grouping and attentional selection. So far, it has been studied primarily under well-controlled visual fixation conditions and using well-controlled stimuli, like isolated bars or patches of grating. If gamma-band activity is to subserve its purported functions outside of the laboratory, it should be present during natural viewing conditions. We recorded neuronal activity with a 252-channel electrocorticographic (ECoG) grid covering large parts of the left hemisphere of 2 macaque monkeys, while they freely viewed natural images. We found that natural viewing led to pronounced gamma-band activity in the visual cortex. In area V1, gamma-band activity during natural viewing showed a clear spectral peak indicative of oscillatory activity between 50 and 80 Hz and was highly significant for each of 65 natural images. Across the ECoG grid, gamma-band activity during natural viewing was present over most of the recorded visual cortex and absent over most remaining cortex. After saccades, the gamma peak frequency slid down to 30-40 Hz at around 80 ms postsaccade, after which the sustained 50- to 80-Hz gamma-band activity resumed. We propose that gamma-band activity plays an important role during natural viewing.


Does diet mediate associations of volume and bouts of sedentary time with cardiometabolic health indicators in adolescents?
Examine the mediating role of diet in the relationship between volume and duration of sedentary time with cardiometabolic health in adolescents. Adolescents (12-19 years) participating in the 2003/04 and 2005/06 U.S. National Health and Nutrition Examination Survey (NHANES) were examined. Cardiometabolic health indicators were body mass index z-scores (zBMI) (n = 1,797) and metabolic syndrome (MetS) (n = 812). An ActiGraph hip-worn accelerometer was used to derive total sedentary time and usual sedentary bout duration. Dietary intake was assessed using two 24-hour dietary recalls. Mediation analyses were conducted to examine five dietary mediators [total energy intake, discretionary foods, sugar-sweetened beverages (SSB), fruits and vegetables, and dietary quality] of the relationship between total sedentary time and usual sedentary bout duration with zBMI and MetS. Total sedentary time was inversely associated with zBMI (β = -1.33; 95% CI -2.53 to -0.13) but attenuated after adjusting for moderate-to-vigorous physical activity. No significant associations were observed between usual sedentary bout duration with zBMI or either sedentary measure with MetS. None of the five dietary variables mediated any of the relationships examined. Further studies are needed to explore associations of specific time periods (e.g., after school) and bout durations with both cardiometabolic health indicators and dietary behaviors.


Transformational Steam Infusion Processing for Resilient and Sustainable Food Manufacturing Businesses.
Here we show how food and beverage manufacturers report more incisive sustainability and product fulfilment outcomes for their business enterprises when innovative processing technologies are used. The reported steam infusion technology heats food materials within a Vaction Pump device so that steam is directed into the food material within a much reduced volume, reducing the use of steam and processing time. This study reports how such technological interventions will enable supply chain stakeholders to demonstrate responsible consumption by connecting assessments for the reduction of greenhouse gas emissions with consumer-focused outcomes such as product quality. The technology reported in this research not only improves operational agility by improving processing speed, but also improves the responsiveness of factory production to changes in demand. Heating procedures are systemic processes in the food industry that can be used to pasteurize, achieve commercially viable shelf-life, and provide cleaning in place. The reported research defines how these technologies can reduce the carbon footprint of products, improve quality attributes, and lower operating costs across supply chains. They provide an important step in developing distributed manufacturing in the food system because the technologies reported here are modular and can be installed into existing operations. The specific technology can reduce energy consumption by 17.3% compared to basic direct steam heating, with a reduction of 277.8 processing hours and 8.7 tonnes GHG emissions per kettle production line each year. Food and beverage manufacturers are increasingly required to report across the sustainability, nutrition, and product quality outcomes of their business enterprises more incisively so that supply chain stakeholders can demonstrate responsible production and consumption. The steam infusion technologies assessed in this research enable alignment to the UN Sustainable Development Goals, specifically SDG12, Responsible Production and Consumption, using in situ data logging in factory trials for novel heating procedures used to process foods.


Choice and interpretation of statistical tests used when competing risks are present.
In clinical cancer research, competing risks are frequently encountered. For example, individuals undergoing treatment for surgically resectable disease may experience recurrence near the removed tumor, metastatic recurrence at other sites, occurrence of second primary cancer, or death resulting from noncancer causes before any of these events. Two quantities, the cause-specific hazard function and the cumulative incidence function, are commonly used to summarize outcomes by event type. Tests for event-specific differences between treatment groups may thus be based on comparison of (a) cause-specific hazards via a log-rank or related test, or (b) the cumulative incidence functions via one of several available tests. Inferential results for tests based on these different metrics can differ considerably for the same cause-specific end point. Depending on the questions of principal interest, one or both metrics may be appropriate to consider. We present simulation study results and discuss examples from cancer clinical trials to illustrate these points and provide guidance for analysis when competing risks are present.


Functional annotation of Fibrobacter succinogenes S85 carbohydrate active enzymes.
Fibrobacter succinogenes is a cellulolytic bacterium that degrades plant cell wall biomass in ruminant animals and is among the most rapidly fibrolytic of all mesophilic bacteria. The complete genome sequence of Fisuc was completed by the DOE Joint Genome Institute in late 2009. Using new expression tools developed at Lucigen and C5-6 Technologies and a multi-substrate screen, 5,760 random shotgun expression clones were screened for biomass-degrading enzymes, representing 2× genome expression coverage. From the screen, 169 positive hits were recorded and 33 were unambiguously identified by sequence analysis of the inserts as belonging to CAZy family genes. Eliminating duplicates, 24 unique CAZy genes were found by functional screening. Several previously uncharacterized enzymes were discovered using this approach and a number of potentially mis-annotated enzymes were functionally characterized. To complement this approach, a high-throughput system was developed to clone and express all the annotated glycosyl hydrolases and carbohydrate esterases in the genome. Using this method, six previously described and five novel CAZy enzymes were cloned, expressed, and purified in milligram quantities.


Mastery and perceived autonomy support are correlates of Dutch diabetes patients' self-management and quality of life.
The aim of this study was to assess the associations between type 2 diabetes patients' mastery and perceived autonomy support and their self-management skills and health-related quality of life (HRQOL). A cross-sectional questionnaire survey was conducted among 3352 patients with type 2 diabetes. Key variables were assessed with validated questionnaires. Patients' mastery and perceived autonomy support correlated positively with their self-management skills (r=0.34, p<0.001; r=0.37, p<0.001) and HRQOL (r=0.37, p<0.001; r=0.15, p<0.001). In the linear regression analysis, mastery and perceived autonomy support were positive correlates of self-management (β=0.23; p<0.001; β=0.25; p<0.001). Patients with more physical or psychological complications had significantly lower scores on mastery, perceived autonomy support, self-management and HRQOL. Our results indicate the importance of mastery in relation to diabetes patients' perceived autonomy support, self-management skills and HRQOL. Since a greater sense of mastery is likely to increase patients' autonomous motivation to cope with their disease, interventions can aim to influence patients' motivational regulation. In addition, we confirmed the need for autonomy support to improve patients' self-management skills. Professionals can be trained to be autonomy-supportive, which relates to person-centered approaches such as motivational interviewing (MI).


Long-term effects of stress reduction on mortality in persons > or = 55 years of age with systemic hypertension.
Psychosocial stress contributes to high blood pressure and subsequent cardiovascular morbidity and mortality. Previous controlled studies have associated decreasing stress with the Transcendental Meditation (TM) program with lower blood pressure. The objective of the present study was to evaluate, over the long term, all-cause and cause-specific mortality in older subjects who had high blood pressure and who participated in randomized controlled trials that included the TM program and other behavioral stress-decreasing interventions. Patient data were pooled from 2 published randomized controlled trials that compared TM, other behavioral interventions, and usual therapy for high blood pressure. There were 202 subjects, including 77 whites (mean age 81 years) and 125 African-American (mean age 66 years) men and women. In these studies, average baseline blood pressure was in the prehypertensive or stage I hypertension range. Follow-up of vital status and cause of death over a maximum of 18.8 years was determined from the National Death Index. Survival analysis was used to compare intervention groups on mortality rates after adjusting for study location. Mean follow-up was 7.6 +/- 3.5 years. Compared with combined controls, the TM group showed a 23% decrease in the primary outcome of all-cause mortality after maximum follow-up (relative risk 0.77, p = 0.039). Secondary analyses showed a 30% decrease in the rate of cardiovascular mortality (relative risk 0.70, p = 0.045) and a 49% decrease in the rate of mortality due to cancer (relative risk 0.49, p = 0.16) in the TM group compared with combined controls. These results suggest that a specific stress-decreasing approach used in the prevention and control of high blood pressure, such as the TM program, may contribute to decreased mortality from all causes and cardiovascular disease in older subjects who have systemic hypertension.


Radioimmunoassay for measurement of thyroglobulin in human serum.
A specific and reproducible double antibody radioimmunoassay for the measurement of thyroglobulin (HTg) in human serum has been developed. Since antithyroglobulin autoantibodies combine with the [(131)I] HTg tracer, antibody-positive sera were rejected for measurement. Specificity is demonstrated in that thyroid analogous such as thyroxine (T(4)), triiodothyronine (T(2)) monoiodotyrosine (MIT) and diiodotyrosine (DIT) did not crossreact. Sera previously reacted with anti-HTg-Sepharose contained no immunoassayable HTg. Finally, sera obtained from patients after total thyroid ablation for thyroid carcinoma did not contain demonstrable HTg. The sensitivity of the assay is 1.6 ng/ml, and HTg was detectable in 74% of 95 normal subjects. The mean concentration was 5.1 ng/ml +/-0.49 SEM (range <1.6-20.7 ng/ml). Day to day variation in HTg levels is large in some euthyroid subjects and nearly absent in others. HTg was detectable in 90% of the sera obtained in 23 pregnant women at delivery in whom a mean concentration of 10.1 ng/ml +/-1.3 SEM was observed. The mean level for the corresponding newborn infants at birth was 29.3 ng/ml +/-4.7 SEM a value significantly higher than the mean maternal HTg concentration (P <0.01). A group of 17 thyrotoxic individuals all had elevated HTg levels; the mean for this group was 344.8 ng/ml +/-90.7 SEM. In the acute phase of subacute thyroiditis HTg was also elevated in all of 12 patients, and the mean for this group was 136.8 ng/ml +/-74.6 SEM.


On the schistosomicidal effect of triclabendazole an experimental study.
Mice were infected with S. mansoni cercariae and divided to three groups: one as control, the others were treated with a single oral dose of PZQ or TCBZ. The efficacy of the drugs was evaluated on the basis of egg excretion, number, sex and distribution of worms, oogram changes and tissue egg load. Results demonstrated that eggs disappeared from the stools in both treated groups, all worms died in the PZQ treated group while in the TCBZ group, worm production amounted to 84%. Male worms were more susceptible to the two drugs, they died earlier. On the fourth week after TCBZ, the few surviving worms returned back from their hepatic shift to the mesenteric veins. By studying the oogram pattern, it was found that PZQ had a direct lethal effect on the mature eggs; TCBZ had a lower effect on egg viability but the oogram findings indicated cessation of egg laying.


Preclinical effects of cannabidiol in an experimental model of migraine.
Migraine is a disabling disorder characterized by recurrent headaches, accompanied by abnormal sensory sensitivity and anxiety. Despite extensive historical use of cannabis in headache disorders, there is limited research on the nonpsychoactive cannabidiol (CBD) for migraine and there is no scientific evidence to prove that CBD is an effective treatment. The effects of CBD are examined here using a calcitonin gene-related peptide (CGRP)-induced migraine model that provides measures of cephalic allodynia, spontaneous pain, altered light sensitivity (photophobia), and anxiety-like behavior in C57BL/6J mice. A single administration of CGRP induced facial hypersensitivity in both female and male mice. Repeated CGRP treatment produced progressively decreased levels in basal thresholds of allodynia in females, but not in males. A single CBD administration protected both females and males from periorbital allodynia induced by a single CGRP injection. Repeated CBD administration prevented increased levels of basal allodynia induced by repeated CGRP treatment in female mice and did not lead to responses consistent with migraine headache as occurs with triptans. Cannabidiol, injected after CGRP, reversed CGRP-evoked allodynia. Cannabidiol also reduced spontaneous pain traits induced by CGRP administration in female mice. Finally, CBD blocked CGRP-induced anxiety in male mice, but failed in providing protection from CGRP-induced photophobia in females. These results demonstrate the efficacy of CBD in preventing episodic and chronic migraine-like states with reduced risk of causing medication overuse headache. Cannabidiol also shows potential as an abortive agent for treating migraine attacks and headache-related conditions such as spontaneous pain and anxiety.


U.S. case report of cerebral phaeohyphomycosis caused by Ramichloridium obovoideum (R. mackenziei): criteria for identification, therapy, and review of other known dematiaceous neurotropic taxa.
We report a case of cerebral phaeohyphomycosis in a 36-year-old male caused by the neurotropic fungus Ramichloridium obovoideum (Matushima) de Hoog 1977 (Ramichloridium mackenziei Campbell et Al-Hedaithy 1993). This man resided in the Middle East, where the fungus appears to be endemic and, possibly, geographically restricted, since all previous reports of brain abscesses due to this organism have been for patients indigenous to this area. As a servant of the Saudi Arabian royal family, he appeared in the United States seeking treatment for chronic weight loss, fatigue, decreased memory, and a more recent 2-week history of right-hand weakness which worsened to involve the entire right upper extremity. On the day prior to his admission, he had a focal motor seizure with rotation of the head and eyes to the right, followed by secondary generalization. A computerized tomogram showed a ring-enhancing hypodense lesion in the left parietal subcortical region with associated edema and mass effect. Diagnosis of a fungal etiology was made following a parietal craniotomy and excisional biopsy by observation of septate, dematiaceous hyphal elements 2 to 3 microm in width on hematoxylin-and-eosin-stained sections from within areas of inflammation and necrosis. Culture of the excised material grew out a dematiaceous mould which was subsequently identified as R. obovoideum. At two months postsurgery and with a regimen of 200 mg of itraconazole twice a day, the patient was doing well and returned to Saudi Arabia. His condition subsequently deteriorated, however, and following a 7-month course of itraconzole, he expired. We use this case to alert clinicians and personnel in clinical mycology laboratories of the pathogenicity of this organism and its potential occurrence in patients with central nervous system signs and symptoms who have resided in the Middle East and to review and/or compare R. obovoideum with other neurotropic, dematiaceous taxa and similar nonneurotropic, dematiaceous species.


Different preloading protocols with constant ephedrine infusion in the prevention of hypotension for elective cesarean section under spinal anesthesia.
Ninety ASA I or II parturients were randomly allocated to three groups: group 10RL, 15RL and 20RL to receive 10, 15 and 20 mL/kg of Ringer's lactate (RL) respectively within 15 minutes (min) before the spinal block. Spinal anesthesia was performed with hyperbaric bupivacaine 12 mg, morphine 100 microg and fentanyl 10 microg. The operating table was tilted to the left and an IV infusion of ephedrine of 3 mg/min was immediately started and continued until umbilical cord clamping in all groups. Hypotension was defined as a drop in mean arterial pressure (MAP) of more than 20% from baseline : this was treated with 10 mg ephedrine IV. The incidence of hypotension was 60%, 36.7% and 13.4% in group 10RL, 15RL and 20RL, respectively (p<0.05). Additional ephedrine dose was the lowest in group 20RL compared to the other groups (p<0.05). The total amount of ephedrine was 49.9 +/- 13.5, 46.4 +/- 13.4 and 38.4 +/- 8.5 mg in group 10RL, 15RL and 20RL, respectively (p <0.05). The incidence of nausea and vomiting in group 20RL was significantly less than in group 10RL (p = 0.02). It was concluded that preloading with 20 mL/kg of RL prior to spinal anesthesia followed by constant ephedrine infusion 3 mg/min after spinal block reduced the incidence of hypotension and of nausea and vomiting and decreased the total amount of ephedrine.


Autoimmunity in the elderly: Implications for cancer.
Immunosenescence is the aging process involving the immune system competencies. These changes imply a reduced level of immunosurveillance against cancer onset and the occurrence of autoimmune phenomena. The clinical presentation of autoimmune diseases in the elderly is characterized in most cases by atypical features, insidious presentation and poor specificity of laboratory parameters. The role of autoimmune reactivity in the elderly either as a consequence of or as a risk factor for cancer development has aroused great interest among clinicians and researchers, as well as the influence of a chronic inflammatory state as a predisposing factor for autoimmunity and cancer occurrence. Particularly, we have investigated the pathogenetic effect of two cell subsets, Treg cells and Th17 lymphocytes, involved in the control mechanisms both of autoimmune reactions and cancer onset, as the possible future approach to treat cancer in older adults.


Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with congenital heart disease.
Congenital heart disease (CHD) with intracardiac/extracardiac shunts is an important etiology of pulmonary arterial hypertension (PAH). The majority of children with congenital cardiac shunts do not develop advanced pulmonary vasculopathy, as surgical repair of the anomalies is now performed early in life. However, if not repaired early, some defects will inevitably lead to pulmonary vascular disease (truncus arteriosus, transposition of the great arteries associated with a ventricular septal defect (VSD), atrioventricular septal defects remarkably in Down syndrome, large, nonrestrictive VSDs, patent ductus arteriosus and related anomalies). The majority of patients are now assigned to surgery based on noninvasive evaluation only. PAH becomes a concern (requiring advanced diagnostic procedures) in about 2-10% of them. In adults with CHD, the prevalence of advanced pulmonary vasculopathy (Eisenmenger syndrome) is around 4-12%.[1] This article will discuss the diagnostic and management approach for PAH associated with CHD (PAH-CHD).


Synthesis of virus DNA and polypeptides by temperature-sensitive mutants of rabbitpox virus.
Eighteen temperature-sensitive (ts) mutants of rabbitpox virus were examined for defects in synthesis of DNA and protein. Two mutants (ts-3 and ts-16) were defective in DNA synthesis (DNA-), since both incorporated significantly less than wild-type amounts of labelled thymidine into acid-precipitable material when infected cells were incubated at the restrictive temperature. Both these mutants gave only the 'early' class of virus polypeptides when infected cell extracts were examined by SDS--polyacrylamide slab gel electrophoresis following incubation at 40 degrees C. Nine of the remaining sixteen DNA+ ts mutants (ts-1, ts-2, ts-6, ts-12, ts-15, ts-17, ts-31, ts-32 and ts-33) synthesized wild-type levels of most virus polypeptides at 40 degrees C; six DNA+ ts mutants (ts-7, ts-8, ts-9, ts-11, ts-23 and ts-24) were defective in the post-translational cleavage of the polypeptides involved in membrane stabilization and particle assembly; one DNA+ ts mutant (ts-14) synthesized only the 'early' class of virus polypeptides, implying that either replicated DNA was not fully functional or that a specific early function was required for late transcription.


Clinical significance of the LacdiNAc-glycosylated prostate-specific antigen assay for prostate cancer detection.
To reduce unnecessary prostate biopsies (Pbx), better discrimination is needed. To identify clinically significant prostate cancer (CSPC) we determined the performance of LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA normalized by prostate volume (LDN-PSAD). We retrospectively measured LDN-PSA, total PSA (tPSA), and free PSA/tPSA (F/T PSA) values in 718 men who underwent a Pbx in 3 academic urology clinics in Japan and Canada (Pbx cohort) and in 174 PC patients who subsequently underwent radical prostatectomy in Australia (preop-PSA cohort). The assays were evaluated using the area under the receiver operating characteristics curve (AUC) and decision curve analyses to discriminate CSPC. In the Pbx cohort, LDN-PSAD (AUC 0.860) provided significantly better clinical performance for discriminating CSPC compared with LDN-PSA (AUC 0.827, P = 0.0024), PSAD (AUC 0.809, P < 0.0001), tPSA (AUC 0.712, P < 0.0001), and F/T PSA (AUC 0.661, P < 0.0001). The decision curve analysis showed that using a risk threshold of 20% and adding LDN-PSA and LDN-PSAD to the base model (age, digital rectal examination status, tPSA, and F/T PSA) permitted avoidance of even more biopsies without missing CSPC (9.89% and 18.11%, respectively vs 2.23% [base model]). In the preop-PSA cohort, LDN-PSA values positively correlated with tumor volume and tPSA and were significantly higher in pT3, pathological Gleason score ≥ 7. Limitations include limited sample size, retrospective nature, and no family history information prior to biopsy. LacdiNAc-glycosylated PSA is significantly better than the conventional PSA test in identifying patients with CSPC. This study was approved by the ethics committee of each institution ("The Study about Carbohydrate Structure Change in Urological Disease"; approval no. 2014-195).


Short-term feed and light deprivation reduces voluntary activity but improves swimming performance in rainbow trout Oncorhynchus mykiss.
Rainbow trout Oncorhynchus mykiss (~ 180 g, 16 °C and < 5 kg m-3) that were feed deprived and kept in total darkness showed a significant increase in critical swimming speed (U crit) between 1 and 12 days of deprivation (from 3.35 to 4.46 body length (BL) s-1) with no increase in maximum metabolic rate (MMR). They also showed a significant decrease in the estimated metabolic rate at 0 BL s-1 over 12 days which leads to a higher factorial aerobic metabolic scope at day 12 (9.38) compared to day 1 (6.54). Routine metabolic rates were also measured in ~ 90 g rainbow trout that were swimming freely in large circular respirometers at 16 °C. These showed decreasing consumption oxygen rates and reductions in the amount of oxygen consumed above standard metabolic rate (a proxy for spontaneous activity) over 12 days, though this happened significantly faster when they were kept in total darkness when compared to a 12:12-h light-dark (LD) photoperiod. Weight loss during this period was also significantly reduced in total darkness (3.33% compared to 4.98% total body weight over 12 days). Immunological assays did not reveal any consistent up- or downregulation of antipathogenic and antioxidant enzymes in the serum or skin mucus of rainbow trout between 1 and 12 days of feed and light deprivation. Overall, short periods of deprivation do not appear to significantly affect the performance of rainbow trout which appear to employ a behavioural energy-sparing strategy, albeit more so in darkness than under a 12:12-h LD regime.


Advances in the chemistry and pharmacology of ecteinascidins, a promising new class of anti-cancer agents.
Ecteinascidins are marine natural products consisting of two or three linked tetrahydroisoquinoline subunits and an active carbinolamine functional group. Their potent antiproliferative activity against a variety of tumor cells has made them attractive candidates for development as anticancer agents. The lead compound, ecteinascidin 743 (ET 743), is currently in phase II clinical trials but the low amounts present in its natural source, the tunicate Ecteinascidia turbinata, made it necessary to develop efficient synthetic procedures. Recent improvements on the original synthesis are reviewed as well as new strategies starting from readily available cyanosafracin B. ET 743 is known to bind to the minor groove of DNA giving rise to a covalent adduct with the exocyclic amino group at position 2 of a guanine in a fashion similar to saframycin antibiotics. Some of the resulting complexes have been studied by a variety of biochemical and spectroscopic methods and also by computer simulations. The rules for sequence specificity have been well established (preferred targets are RGC and YGG, where R and Y stand for purine and pyrimidine, respectively), and it has been shown that binding of ET 743 to DNA is accompanied by minor groove widening and DNA bending towards the major groove. Although the precise target for antitumor action remains to be unambiguously defined, a role in affecting the transcriptional regulation of some inducible genes is rapidly emerging.


Inflammatory tendencies and overproduction of IL-17 in the colon of young NOD mice are counteracted with diet change.
Dietary factors influence diabetes development in the NOD mouse. Diet affects the composition of microbiota in the distal intestine, which may subsequently influence intestinal immune homeostasis. However, the specific effects of antidiabetogenic diets on gut immunity and the explicit associations between intestinal immune disruption and type 1 diabetes onset remain unclear. Gut microbiota of NOD mice fed a conventional diet or ProSobee formula were compared using gas chromatography. Colonic lamina propria immune cells were characterized in terms of activation markers, cytokine mRNA and Th17 and Foxp3(+) T-cell numbers, using real-time PCR and flow cytometry. Activation of diabetogenic CD4 T-cells by purified B-cells was assessed in both groups. Immune tolerance to autologous commensal bacteria was evaluated in vitro using thymidine-incorporation tests. Young NOD mice showed a disturbed tolerance to autologous commensal bacteria. Increased numbers of activated CD4 T-cells and (CD11b(+)CD11c(+)) dendritic cells and elevated levels of Th17 cells and IL23 mRNA were moreover observed in colon lamina propria. These phenomena were abolished when mice were fed an antidiabetogenic diet. The antidiabetogenic diet also altered the expression levels of costimulatory molecules and the capacity of peritoneal B-cells to induce insulin-specific CD4 T-cell proliferation. Young NOD mice show signs of subclinical colitis, but the symptoms are alleviated by a diet change to an antidiabetogenic diet. Disrupted immune tolerance in the distal intestine may influence peritoneal cell pools and B-cell-mediated activation of diabetogenic T-cells.


Palmitoylation and membrane interactions of the neuroprotective chaperone cysteine-string protein.
Cysteine-string protein (CSP) is an extensively palmitoylated DnaJ-family chaperone, which exerts an important neuroprotective function. Palmitoylation is required for the intracellular sorting and function of CSP, and thus it is important to understand how this essential modification of CSP is regulated. Recent work identified 23 putative palmitoyl transferases containing a conserved DHHC domain in mammalian cells, and here we show that palmitoylation of CSP is enhanced specifically by co-expression of the Golgi-localized palmitoyl transferases DHHC3, DHHC7, DHHC15, or DHHC17. Indeed, these DHHC proteins promote stable membrane attachment of CSP, which is otherwise cytosolic. An inverse correlation was identified between membrane affinity of unpalmitoylated CSP mutants and subsequent palmitoylation: mutants with an increased membrane affinity localize to the endoplasmic reticulum (ER) and are physically separated from the Golgi-localized DHHC proteins. Palmitoylation of an ER-localized mutant could be rescued by brefeldin A treatment, which promotes the mixing of ER and Golgi membranes. Interestingly though, the palmitoylated mutant remained at the ER following brefeldin A washout and did not traffic to more distal membrane compartments. We propose that CSP has a weak membrane affinity that allows the protein to locate its partner Golgi-localized DHHC proteins directly by membrane "sampling." Mutations that enhance membrane association prevent sampling and lead to accumulation of CSP on cellular membranes such as the ER. The coupling of CSP palmitoylation to Golgi membranes may thus be an important requirement for subsequent sorting.


Evaluation of self-sampling-based cervical cancer screening strategy using HPV Selfy CE-IVD test coupled with home-collection kit: a clinical study in Italy.
Primary human papillomaviruses (HPV) cervical cancer screening can be strengthened by offering home-collection of biological specimen as a valuable option to increase screening coverage. As recommended by World Health Organization (WHO), screening programs should consider whether the inclusion of HPV self-sampling as a complementary option within their existing screening algorithms could address the gaps in current coverage. However, few HPV screening tests are validated for self-sampling according to international guidelines. This study aimed to test a self-sampling-based screening strategy, complementary to the main screening program based on clinician-collected cervical samples. The study took place in Trieste, Italy, and it aimed to evaluate the feasibility of self-testing at home under an opt-in system during COVID-19 pandemic in order to exploit self-sampling to reduce the screening delay generated by the lockdown. 500 women, who should have received the screening call in 2020, were asked, via phone call, to participate in the study. To whom agreed, a home-collection kit, including a vaginal dry swab for specimen collection, was sent. The recipients performed the sample self-collection and sent back the swab through traditional mail using a prepaid envelope. Once received by the hospital, the samples were analyzed with HPV Selfy (Ulisse BioMed, Italy), a CE-IVD HPV screening test specifically validated for self-collection. Results were further compared using cobas® 4800 HPV (Roche, Switzerland). 80% women sent back their swab, showing one of the highest return rate obtained in comparable studies. 34 HPV-positive women were followed up and underwent the Pap test, that revealed 8 low squamous intraepithelial lesions (LSIL) cases, later triaged to colposcopy. HPV Selfy was confirmed to be an adequate test for self-sampling-based screening. This study further confirmed the feasibility of self-test at home screening strategy based on self-sampling with an opt-in system as a support method to enhance cervical cancer screening coverage in Italy. Enrolled women showed a high appreciation for this approach. HPV Selfy test demonstrated to be a valuable assay for cervical cancer screening based on home self-collection. ASUGI Trieste n. 16008/2018 and amendment 02-11/09/2020.


Characterising the Physiological Responses of Chinook Salmon (Oncorhynchus tshawytscha) Subjected to Heat and Oxygen Stress.
In New Zealand, during the hottest periods of the year, some salmon farms in the Marlborough Sounds reach water temperatures above the optimal range for Chinook salmon. High levels of mortality are recorded during these periods, emphasising the importance of understanding thermal stress in this species. In this study, the responses of Chinook salmon (Oncorhynchus tshawytscha) to chronic, long-term changes in temperature and dissolved oxygen were investigated. This is a unique investigation due to the duration of the stress events the fish were exposed to. Health and haematological parameters were analysed alongside gene expression results to determine the effects of thermal stress on Chinook salmon. Six copies of heat shock protein 90 (HSP90) were discovered and characterised: HSP90AA1.1a, HSP90AA1.2a, HSP90AA1.1b, HSP90AA1.2b, HSP90AB1a and HSP90AB1b, as well as two copies of SOD1, named SOD1a and SOD1b. The amino acid sequences contained features similar to those found in other vertebrate HSP90 and SOD1 sequences, and the phylogenetic tree and synteny analysis provided conclusive evidence of their relationship to other vertebrate HSP90 and SOD1 genes. Primers were designed for qPCR to enable the expression of all copies of HSP90 and SOD1 to be analysed. The expression studies showed that HSP90 and SOD1 were downregulated in the liver and spleen in response to longer term exposure to high temperatures and lower dissolved oxygen. HSP90 was also downregulated in the gill; however, the results for SOD1 expression in the gill were not conclusive. This study provides important insights into the physiological and genetic responses of Chinook salmon to temperature and oxygen stress, which are critical for developing sustainable fish aquaculture in an era of changing global climates.


Violence in health care. What nurse managers need to know.
About 10% to 15% of the violence in the United States occurs in the workplace. Health care workers in particular face dramatically higher risks for nonfatal assault. Nonviolent crisis interventions and a detailed violence management and prevention plan prepare nurse managers for any situation.


A SARS-CoV-2 Cluster in an Acute Care Hospital.
Little is known about clusters of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in acute care hospitals. To describe the detection, mitigation, and analysis of a large cluster of SARS-CoV-2 infections in an acute care hospital with mature infection control policies. Descriptive study. Brigham and Women's Hospital, Boston, Massachusetts. Patients and staff with cluster-related SARS-CoV-2 infections. Close contacts of infected patients and staff were identified and tested every 3 days, patients on affected units were preemptively isolated and repeatedly tested, affected units were cleaned, room ventilation was measured, and specimens were sent for whole-genome sequencing. A case-control study was done to compare clinical interactions, personal protective equipment use, and breakroom and workroom practices in SARS-CoV-2-positive versus negative staff. Description of the cluster, mitigation activities, and risk factor analysis. Fourteen patients and 38 staff members were included in the cluster per whole-genome sequencing and epidemiologic associations. The index case was a symptomatic patient in whom isolation was discontinued after 2 negative results on nasopharyngeal polymerase chain reaction testing. The patient subsequently infected multiple roommates and staff, who then infected others. Seven of 52 (13%) secondary infections were detected only on second or subsequent tests. Eight of 9 (89%) patients who shared rooms with potentially contagious patients became infected. Potential contributing factors included high viral loads, nebulization, and positive pressure in the index patient's room. Risk factors for transmission to staff included presence during nebulization, caring for patients with dyspnea or cough, lack of eye protection, at least 15 minutes of exposure to case patients, and interactions with SARS-CoV-2-positive staff in clinical areas. Whole-genome sequencing confirmed that 2 staff members were infected despite wearing surgical masks and eye protection. Findings may not be generalizable. SARS-CoV-2 clusters can occur in hospitals despite robust infection control policies. Insights from this cluster may inform additional measures to protect patients and staff. None.


Advances in shotgun proteomics and the analysis of membrane proteomes.
The emergence of shotgun proteomics has facilitated the numerous biological discoveries made by proteomic studies. However, comprehensive proteomic analysis remains challenging and shotgun proteomics is a continually changing field. This review details the recent developments in shotgun proteomics and describes emerging technologies that will influence shotgun proteomics going forward. In addition, proteomic studies of integral membrane proteins remain challenging due to the hydrophobic nature in integral membrane proteins and their general low abundance levels. However, there have been many strategies developed for enriching, isolating and separating membrane proteins for proteomic analysis that have moved this field forward. In summary, while shotgun proteomics is a widely used and mature technology, the continued pace of improvements in mass spectrometry and proteomic technology and methods indicate that future studies will have an even greater impact on biological discovery.


Alternative splicing and co-option of transposable elements: the case of TMPO/LAP2α and ZNF451 in mammals.
Transposable elements constitute a large fraction of vertebrate genomes and, during evolution, may be co-opted for new functions. Exonization of transposable elements inserted within or close to host genes is one possible way to generate new genes, and alternative splicing of the new exons may represent an intermediate step in this process. The genes TMPO and ZNF451 are present in all vertebrate lineages. Although they are not evolutionarily related, mammalian TMPO and ZNF451 do have something in common-they both code for splice isoforms that contain LAP2alpha domains. We found that these LAP2alpha domains have sequence similarity to repetitive sequences in non-mammalian genomes, which are in turn related to the first ORF from a DIRS1-like retrotransposon. This retrotransposon domestication happened separately and resulted in proteins that combine retrotransposon and host protein domains. The alternative splicing of the retrotransposed sequence allowed the production of both the new and the untouched original isoforms, which may have contributed to the success of the colonization process. The LAP2alpha-specific isoform of TMPO (LAP2α) has been co-opted for important roles in the cell, whereas the ZNF451 LAP2alpha isoform is evolving under strong purifying selection but remains uncharacterized.


Deformation twinning of ferrocene crystals assisted by the rotational mobility of cyclopentadienyl rings.
Deformation twinning, which is a type of plastic deformation, has been particularly investigated in metal materials. However, only a few examples are found in organic solids. We observed mechanical twinning deformation on a simple ferrocene crystal, which is considered the most representative organometallic compound, and evaluated the crystal structures under the twinning state and the shear deformation characteristics by single-crystal X-ray diffraction analysis and uniaxial compression tests. The structural analyses showed the molecular rearrangement during twinning deformation. The shear deformation properties depend on the rotational mobility of the cyclopentadienyl rings in comparison with crystals of nickelocene, ruthenocene, and mixed crystals of ferrocene/ruthenocene.


Cuban Meningococcal BC Vaccine: Experiences & Contributions from 20 Years of Application.
This paper reviews 20 years of experience and scientific contributions of the Cuban meningococcal BC vaccine (VA-MENGOC-BC®) obtained by the Finlay Institute in Havana, Cuba. The vaccine is the first of its type in the world that is safe, effective, and commercially available for preventing meningococcal disease caused by serogroup B meningococcus; it is also effective against serogroup C. VA-MENGOC-BC® has shown satisfactory results, with no serious adverse events, after application of approximately 55 million doses in some 15 countries. Also included is background information on meningococcal disease, as well as the main characteristics of VA-MENGOC-BC®, the strategy used for controlling meningococcal disease and its prevention in Cuba, and a summary of the main scientific results obtained in basic research, development, clinical evaluation, and post-marketing results (safety, efficacy-effectiveness, post-vaccination adverse events, etc.) in Cuba and elsewhere.


Nanoparticles influence miscibility in LCST polymer blends: from fundamental perspective to current applications.
Polymer blending is an effective method that can be used to fabricate new versatile materials with enhanced properties. The blending of two polymers can result in either a miscible or an immiscible polymer blend system. This present review provides an in-depth summary of the miscibility of LCST polymer blend systems, an area that has garnered much attention in the past few years. The initial discourse of the present review mainly focuses on process-induced changes in the miscibility of polymer blend systems, and how the preparation of polymer blends affects their final properties. This review further highlights how nanoparticles induce miscibility and describes the various methods that can be implemented to avoid nanoparticle aggregation. The concepts and different state-of-the-art experimental methods which can be used to determine miscibility in polymer blends are also highlighted. Lastly, the importance of studying miscible polymer blends is extensively explored by looking at their importance in barrier materials, EMI shielding, corrosion protection, light-emitting diodes, gas separation, and lithium battery applications. The primary goal of this review is to cover the journey from the fundamental aspects of miscible polymer blends to their applications.


Evaluation of tools used to measure calcium and/or dairy consumption in adults.
To identify and critique tools for the assessment of Ca and/or dairy intake in adults, in order to ascertain the most accurate and reliable tools available. A systematic review of the literature was conducted using defined inclusion and exclusion criteria. Articles reporting on originally developed tools or testing the reliability or validity of existing tools that measure Ca and/or dairy intake in adults were included. Author-defined criteria for reporting reliability and validity properties were applied. Studies conducted in Western countries. Adults. Thirty papers, utilising thirty-six tools assessing intake of dairy, Ca or both, were identified. Reliability testing was conducted on only two dairy and five Ca tools, with results indicating that only one dairy and two Ca tools were reliable. Validity testing was conducted for all but four Ca-only tools. There was high reliance in validity testing on lower-order tests such as correlation and failure to differentiate between statistical and clinically meaningful differences. Results of the validity testing suggest one dairy and five Ca tools are valid. Thus one tool was considered both reliable and valid for the assessment of dairy intake and only two tools proved reliable and valid for the assessment of Ca intake. While several tools are reliable and valid, their application across adult populations is limited by the populations in which they were tested. These results indicate a need for tools that assess Ca and/or dairy intake in adults to be rigorously tested for reliability and validity.


[Survival and morbidity of infants with necrotizing enterocolitis treated with surgery].
to determine the survival rate and type of morbidity during the first year of life of infants with necrotizing enterocolitis (NED) who underwent to surgical treatment. a comparative and descriptive study was performed. Thirty two children with NEC (19 deaths and 13 survivals) who underwent to surgery during neonatal period were studied. Perinatal conditions, surgical procedures and findings, morbidity and survival rate during the first year of life were registered. all patients underwent to laparotomy, except three patients who died and were managed with peritoneal drainage only. During the first year of life, cholestasis and intestinal obstruction were the main causes of morbidity in survivals and deaths. Survival rate during neonatal period was 78 %, and 40.6% in the first year of life. morbidities during the first year of life were related to surgery. In this series, there was a high survival rate in neonatal period, which diminished in the first year of life.


Renal and cardiac assessment of living kidney donor candidates.
Living kidney donation provides the best therapeutic outcomes for eligible patients with end-stage renal disease. To ensure suitability for living kidney donation, donor candidates undergo a thorough medical, surgical, and psychosocial evaluation by a multidisciplinary transplant assessment team. Numerous guidelines are available to assist clinicians in the process of donor evaluation and selection. These guidelines outline the minimum recommended requirements for donor screening and additional tests that are indicated when abnormalities arise; however, evidence suggests that some of these additional tests might not be required in certain donor candidates. Measured glomerular filtration rate (GFR) using isotopic methods is more accurate than estimated GFR for the assessment of renal function; however, a new clinical tool might enable the identification of donor candidates for whom nuclear medicine renal scans are not needed. Persistent isolated microscopic haematuria caused by urologic or glomerular diseases can preclude donation and such abnormalities can often be identified by kidney biopsy. Cystoscopy might not be useful for young patients, however, owing to the rarity of urological cancers in this population. Currently, no evidence exists to support the notion that donor candidates at low-risk of cardiac events should undergo additional preoperative cardiovascular evaluation before donation. Reducing and/or eliminating the need for additional testing has the potential to enhance efficiency in the donor evaluation process, improve patient satisfaction, and increase access to living donor kidney transplantation.


Prolonged service intervals in cattle.
A trial based on progesterone radioimmunoassay of milk samples is described. Samples from 2274 cows in 14 herds were collected on the day of insemination and 7, 23 and 30 days later, unless a return to service occurred before the designated sample date. Two additional samples were collected from cows which returned to service more than 35 days after the first service, one on the day of the return and another seven days later. All six samples from these cows were assayed for progesterone concentration. Late returns, defined as returns to oestrus 36 or more days after mating, occurred in 8.6% of the cows. Milk progesterone assay results indicate that of these apparently late-returning cows, 55.9% suffered a loss of the conceptus, 22.1% had not been detected in oestrus around 21 days after first insemination, 11.8% were in anoestrus at insemination, 5.6% conceived to the insemination and were pregnant when thought to have had a late return, 2.6% were in prooestrus or dioestrus at insemination and 2.1% went into anoestrus after an oestrus insemination. The average prevalence of late returns after the 35th day (8.6%) and the estimated incidence of losses of concepta (4.8%) are lower than those reported in comparable studies elsewhere. Although many of the late-return cows were mated again and conceived, this syndrome nevertheless contributes significantly to the wastage rate, at least in New Zealand dairy herds with their strictly seasonal calving pattern. The implications of these findings are discussed and recommendations for their prevention are made where appropriate.


L'expérience de l'accouchement en milieu surveillé dans la province d'Essaouira au Maroc: Quelle réalité?
RésuméUne expérience positive de l'accouchement (EPA) est fondamentale pour des soins maternels de qualité. Toutefois, de nombreuses femmes subissent des comportements non respectueux lors de ce moment crucial. Au Maroc, peu d'études ont mesuré cette expérience, et les éléments l'influençant demeurent insuffisamment documentés. Nous avons conduit une recherche mixte dans la province d'Essaouira entre avril et décembre 2021. Notre enquête, basée sur un questionnaire, a sollicité l'avis de 240 femmes issues de huit centres de santé choisis au hasard. Par ailleurs, des entretiens semi-directifs ont été conduits avec 20 femmes, 47 professionnels de santé et quatre responsables administratifs. Les données quantitatives ont été soumises à des analyses descriptives, bi- et multivariées, tandis que les entretiens ont été analysés selon une approche de contenu thématique. Les données révèlent que 59.2% des participantes ont eu une expérience défavorable lors de leur dernier accouchement. Parmi elles, la majorité a déploré des soins non consentis (86.7%), un manque de respect de leur intimité (45.4%) et des abus verbaux (25%). L'EPA était principalement associée à la qualité de l'environnement de l'accouchement, au soutien pour l'allaitement, à la propreté des installations, au type d'établissement (privé) et à l'absence de complications médicales pendant le travail. Les entretiens ont révélé que le manque de motivation des professionnels de santé, l'absence de formation continue appropriée et des lacunes organisationnelles et managériales ont affecté l'EPA. Notre étude souligne le besoin crucial de formation continue axée sur le respect des patients, l'éthique et la déontologie, et met en lumière l'importance d'une politique motivante pour les professionnels de santé, notamment dans le secteur public.


Investigation of the transmigrated canine in an orthodontic patient population.
To investigate the prevalence, demographic and clinical characteristics of transmigrated canines in a south Indian orthodontic patient population. Retrospective observational study. Manipal University, Manipal, India. Panoramic radiographs of 3500 patients were examined and data collected regarding the number and side of transmigrated canines, sex and age of patients, any other associated pathologies and subsequent treatment. Transmigrated canines were classified according to Mupparapu's classification. The prevalence of transmigrated canines in this population was found to be 0.46% of which, seven were males (age: 17-51 years) and nine were females (age: 17-35 years). All transmigrated canines were unilateral and impacted. Eleven canines migrated from the left to the right side, and five migrated from the right to the left. Of the 16 patients, 13 had retained primary canines and 3 had exfoliated primary canines. Eight canines exhibited a type 1 transmigratory pattern, type 2, type 4 and type 5 transmigratory patterns were exhibited by two canines each. One of the canines was classified as type 3. Three canines were associated with dentigerous cyst formation. Four cases were treated by orthodontic traction, while one was removed surgically. Others were observed periodically. Diagnosis of transmigration at earlier stages is important to prevent more complex occlusal problems.


[In vitro antimicrobial activity of cefpirome compared to other broad-spectrum beta-lactam drugs against 804 clinical isolates from 9 Brazilian hospitals].
To evaluate the in vitro activity of the fourth-generation cephalosporin cefpirome in comparison to that of ceftazidime, ceftriaxone, cefotaxime and imipenem in a multicenter study involving nine hospitals from six cities (four States). A total of 804 isolates from patients hospitalized in either intensive care units or Oncology/Hematology units was evaluated. The isolates were collected between June and November of 1995, i.e. before cefpirome became commercially available in Brazil, and susceptibility tested by broth microdilution following the NCCLS procedures. All isolates resistant to cefpirome were retested by E-test. Against Enterobacteriaceae (n = 344), cefpirome demonstrated an activity 2 to 32-fold higher than that of the third-generation cephalosporins (TGCs) and similar to that of imipenem. The percentages of Enterobacteriaceae susceptible were: 88%, 69% and 96% for cefpirome, TGCs and imipenem, respectively. The cefpirome spectrum was greater or equal than that of imipenem against Citrobacter freundii, Enterobacter aerogenes, Morganella morganii and Serratia marcescens. Against Acinetobacter sp. (n = 77), cefpirome was slightly more active than ceftazidime; however, the percentages of isolates resistant to these compounds were high (84% and 88%, respectively). The activities of cefpirome, ceftazidime and imipenem were very similar against P. aeruginosa isolates (n = 128), with MIC50(mg/ml)/percent susceptible of 8/59%, 8/62% and 4/62% respectively. Against aerobic gram-positive bacteria, the cefpirome activity was 4 to 16-fold higher than that of TGCs but 2 to 8-fold lower than that of imipenem. The results suggest that, in Brazil, cefpirome has a spectrum of activity which is higher than that of the TGCs against aerobic gram-negative (Enterobacteriaceae and non-Enterobacteriaceae) and gram-positive bacteria and similar to that of imipenem against some Enterobacteriaceae species and P. aeruginosa.


Strains of CHO-K1 cells resistant to Pseudomonas exotoxin A and cross-resistant to diphtheria toxin and viruses.
We have investigated two phenotypically distinct types of mutants of CHO-K1 cells that are resistant to Pseudomonas exotoxin A due to a defect in the delivery of active toxin to the target site in the cell, elongation factor 2. Both types contain normal levels of toxin-sensitive elongation factor-2. Hybridization studies have shown that these cells fall into two distinct complementation groups. One group, designated DPVr, is resistant to Pseudomonas toxin, diphtheria toxin, and four enveloped RNA viruses. This group is also hypersensitive to ricin. The resistance of this group is apparently related to a defect in a mechanism for the acidification of endocytic vesicles. The other group, designated PVr, is resistant to Pseudomonas toxin and to three enveloped RNA viruses. The resistance of this group appears to be related to a defect in a cellular mechanism required for the maturation of Sindbis virus that is likewise required for the entry of active Pseudomonas toxin.


Design and implementation of an end tidal CO2 simulator for the evaluation of clinical gas analysers.
This paper presents a new technique to determine the dynamic and frequency response of capnographs using a custom built 'EtCO2 simulator system'. Capnographs are devices that use CO2 from a patients' expired breath to monitor the cardiopulmonary status during anaesthesia and mechanical ventilation. Capnographs at present are routinely calibrated via a static calibration method only. The dynamic response of the capnographs is not accounted for. The frequency and time response are important as they determine if capnographs can be used in high frequency and pediatric ventilation schemes. Experiments performed using the method described in this paper proved that old capnographs usually do not satisfy the manufacturer quoted specifications for time and frequency response. Therefore, a routine check for capnographs is recommended. The method can also be used to verify manufacturer quoted specifications. The EtCO2 simulator system, designed and constructed simulates human respiration cycle. The gas sources used are 5% CO2 and room air that can be switched alternatively. Both supplies are pressure regulated and connected through non-return valves to electric valves. The valves are microprocessor controlled and the on/off time is user defined allowing a wide range of waveforms to be simulated. The output from the simulator is delivered to capnograph. Capnograms are captured by digital video recording. The captured video in 'avi' file format is then converted into individual frames. These frames are converted into digital data through image processing in Matlab. The data obtained is subjected to extensive analysis to determine the frequency and time response of the respective capnograph.


Varying Inoculum Dose to Assess the Roles of the Immune Response and Target Cell Depletion by the Pathogen in Control of Acute Viral Infections.
It is difficult to determine whether an immune response or target cell depletion by the infectious agent is most responsible for the control of acute primary infection. Both mechanisms can explain the basic dynamics of an acute infection-exponential growth of the pathogen followed by control and clearance-and can also be represented by many different differential equation models. Consequently, traditional model comparison techniques using time series data can be ambiguous or inconclusive. We propose that varying the inoculum dose and measuring the subsequent infectious load can rule out target cell depletion by the pathogen as the main control mechanism. Infectious load can be any measure that is proportional to the number of infected cells, such as viraemia. We show that a twofold or greater change in infectious load is unlikely when target cell depletion controls infection, regardless of the model details. Analyzing previously published data from mice infected with influenza, we find the proportion of lung epithelial cells infected was 21-fold greater (95% confidence interval 14-32) in the highest dose group than in the lowest. This provides evidence in favor of an alternative to target cell depletion, such as innate immunity, in controlling influenza infections in this experimental system. Data from other experimental animal models of acute primary infection have a similar pattern.


Long-term retention of a spatial mental model for younger and older adults.
Mental models are knowledge structures that are used to describe, predict, and explain the system that they represent. Mental models can be useful for both younger and older adults. Past research (Gilbert & Rogers, 1999, Journal of Gerontology: Psychological Sciences, 54B, P246-P255) indicated that both younger and older adults were able to acquire and utilize a new spatial mental model. Younger and older adult participants from that research returned after a 2-week interval and a group of younger adult participants returned after 4 weeks to determine if their mental model was retained over time. Retention was best for the younger adult 2-week group; performance did not differ for the older adult 2-week and younger adult 4-week groups. Participants who were able to reconstruct the map initially were able to utilize the information very well, regardless of age or retention interval. In addition, both younger and older adults who showed lower initial retention benefited from a brief study time. Implications for refresher training are discussed.


Telephone survey of service-user experiences of a telephone-based mental health triage service.
The participation of service users in all aspects of mental health service delivery including policy development, service planning and evaluation is increasingly an expectation of contemporary mental health care. Although there are a growing number of publications reporting service-user perspectives in the evaluation of mental health services, little attention has been paid to the views of service users about mental health triage services. The purpose of the study reported here was to examine service-users' (consumers and informal carers) experiences of a telephone-based mental health triage service. Using a framework developed from the World Health Organisation's elements of responsiveness, we conducted structured telephone interviews with service users who had contacted a telephone-based mental health triage service in regional Victoria, Australia. The main findings of the study were that consumers experienced more difficulty than carers in accessing the service and that, although most participants were satisfied, only a minority reported being involved in decision-making. Further work is needed to improve accessibility of mental health triage services and to investigate barriers to consumer self-referral. Professional development and practice support systems should be established to support mental health triage nurses in the development of collaborative, consumer-focused care.


[Activation of (ADP-ribose) polymerase by DNA fragmented by micrococcal nuclease and DNAase I].
Activation of (ADP-ribose) polymerase by DNA fragments obtained by digestion of calf thymus DNA with micrococcal nuclease and DNAase I was studied. It was found that activation of the enzyme is due to its interaction with the terminal parts of double-stranded DNA fragments, the level of activation being independent of the size of DNA fragments.


Positive effects of the Beatalk technique on speech characteristics of young adults with intellectual disability.
Background: The Beatalk technique is a speech therapy method, based on human beatboxing, involving intense, rapid repetitions of speech-like sounds. The goals of the current feasibility study were to test its effect in enhancing articulation accuracy and voice measures in a small group of adults with intellectual disability (ID), using a wide range of measures of verbal communication, and to refine the treatment protocol. Methods: A group pre-test-post-test experimental design was used (n = 12). Treatment consisted of ten weekly group sessions of 40 min, each followed by two self-practice sessions. Changes in speech intelligibility, voice, and communication skills were assessed. Results: The findings indicate significant improvements in speech production and intelligibility measures (Percentage of Consonant Correct, and staff-member intelligibility scores), voice measures (vocal loudness, Harmonic-Noise-Ratio, shimmer, and jitter) and staff-member communication scores. Implications: These results extend our understanding of the effects of the Beatalk technique, and suggest that it may have potential as an effective intervention for adults with ID. As the experimental design is limited in its ability to yield strong conclusions, further controlled studies are required.


Aromatic residue position on the nonpolar face of class a amphipathic helical peptides determines biological activity.
The apolipoprotein A-I mimetic peptide 4F (Ac-DWFKAFYDKVAEKFKEAF-NH(2)), with four Phe residues on the nonpolar face of the amphipathic alpha-helix, is strongly anti-inflammatory, whereas two 3F analogs (3F(3) and 3F(14)) are not. To understand how changes in helix nonpolar face structure affect function, two additional 3F analogs, Ac-DKLKAFYDKVFEWAKEAF-NH(2) (3F-1) and Ac-DKWKAVYDKFAEAFKEFL-NH(2) (3F-2), were designed using the same amino acid composition as 3F(3) and 3F(14). The aromatic residues in 3F-1 and 3F-2 are near the polar-nonpolar interface and at the center of the nonpolar face of the helix, respectively. Like 4F, but in contrast to 3F(3) and 3F(14), these peptides effectively inhibited lytic peptide-induced hemolysis, oxidized phospholipid-induced monocyte chemotaxis, and scavenged lipid hydroperoxides from low density lipoprotein. High pressure liquid chromatography retention times and monolayer exclusion pressures indicated that there is no direct correlation of peptide function with lipid affinity. Fluorescence studies suggested that, although the peptides bind phospholipids similarly, the Trp residue in 4F, 3F-1, and 3F-2 is less motionally restricted than in 3F(3) and 3F(14). Based on these results and molecular modeling studies, we propose that the arrangement of aromatic residues in class A amphipathic helical molecules regulates entry of reactive oxygen species into peptide-phospholipid complexes, thereby reducing the extent of monocyte chemotaxis, an important step in atherosclerosis.


EjMYB8 Transcriptionally Regulates Flesh Lignification in Loquat Fruit.
Transcriptional regulatory mechanisms underlying lignin metabolism have been widely studied in model plants and woody trees, but seldom in fruits such as loquat, which undergo lignification. Here, twelve EjMYB genes, designed as EjMYB3-14, were isolated based on RNA-seq. Gene expression indicated that EjMYB8 and EjMYB9 were significantly induced in fruit with higher lignin content resulting from storage at low temperature (0°C), while two treatments (low temperature conditioning, LTC; heat treatment, HT) both alleviated fruit lignification and inhibited EjMYB8 and EjMYB9 expression. Dual-luciferase assays indicated that EjMYB8, but not EjMYB9, could trans-activate promoters of lignin-related genes EjPAL1, Ej4CL1 and Ej4CL5. Yeast one-hybrid assay indicated that EjMYB8 physically bind to Ej4CL1 promoter. Furthermore, the putative functions of EjMYB8 were verified using transient over-expression in both N. tabacum and loquat leaves, which increased lignin content. Moreover, combination of EjMYB8 and previously isolated EjMYB1 generated strong trans-activation effects on the Ej4CL1 promoter, indicating that EjMYB8 is a novel regulator of loquat fruit lignification.


Insertional mutagenesis affecting programmed cell death leads to thymic hyperplasia and altered thymopoiesis.
The mouse mutant Ft displays thymic hyperplasia and fused toes (Ft) of the forelimbs. Both phenotypic abnormalities are caused by transgene insertion in the D region of chromosome 8. While the forelimb defect is probably caused by developmentally dysregulated programmed cell death, the mechanism underlying thymic hyperplasia has not been characterized. In this work, we show that expansion of the thymocyte compartment progresses with time, is polyclonal, and affects all major thymocyte subsets, including the earliest CD4-8- subset, i.e., CD44+ CD25- cells; hyperplasia is not an autonomous property of mutant T cells, but is caused indirectly by a primary defect in thymic stromal. The rate of cell division and the cell turnover of immature CD4-8- and CD4+8+ thymocytes under steady state conditions are not altered in hyperplastic Ft thymi. Immature CD4+8+ thymocytes of mutant mice, however, are less susceptible to induction in vitro of programmed cell death by different modes (TCR cross-linking, cortisone, or radiation). Increased production of thymocytes results in increased export of T cells, yet the size and composition of the peripheral T cell pool are normal. Overproduction of immature CD4+8+ thymocytes is offset partly by a reduced conversion rate of CD4+8+ double positive to single positive thymocyte growth control by epithelial cells, and may serve as a model to study the regulation of early thymopoiesis.


Ovarian torsion of mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman: A case report.
Adnexal torsion is 1 of the most common emergency gynecological disease. It is more often diagnosed in reproductive age, but rarely in postmenopausal women. The clinical symptoms of adnexal torsion are nonspecific in postmenopausal women. Epithelial ovarian tumors are common in adults, and the risk of malignancy increases with age, especially after menopause. So, it is difficult to diagnose adnexal torsion precisely compared with reproductive women, and most cases of adnexal torsion with postmenopausal women are diagnosed as a malignancy preoperatively. We report a case of ovarian torsion with mixed epithelial tumor misdiagnosed as a malignancy in postmenopausal woman. A 65-year-old woman presented lower left abdominal pain, and there was slight abdominal distension, but no tenderness or rebound tenderness on abdominal palpation. Radiologic assessments showed a huge multiseptated cystic mass with solid portion in the left ovary, and malignancy was suspected. The test for serum tumor markers revealed normal levels of cancer antigen 125 (CA-125). The patient underwent a laparotomy and there was torsion of the left ovary. We conducted frozen biopsy of left ovary for confirming malignancy before performing staging surgery. The result of a frozen section biopsy confirmed a borderline Brenner tumor associated with a benign mucinous tumor. Subsequently, total hysterectomy and right salpingo-oophorectomy were performed. The operation was completed without addition procedures LESSONS:: Ovarian torsion is benign in most cases and malignancy is rare. Although very rare, ovarian torsion can occur in postmenopausal women, and it should be taken into consideration that the possibility of malignancy is low in postmenopausal women with normal CA-125 levels. Instead of performing staging surgery, it appears to be appropriate to carry out surgery based on the result of intraoperative frozen section biopsy so that we were able to avoid unnecessary surgical procedures.


The prevalence of aspirin resistance in patients with metabolic syndrome.
Aspirin is recommended for primary prevention in patients with metabolic syndrome (MetS). In this study, we evaluated aspirin resistance in MetS patients. The study included 32 patients (23 males, 9 females; mean age 60.7+/-11.4 years) with the diagnosis of MetS, according to the criteria of the International Diabetes Federation. Aspirin resistance was determined by the PFA-100 analysis (Platelet Function Analyzer). The results were compared with a control group of 30 patients (16 males, 14 females; mean age 61.6+/-7.3 years) without MetS. All the patients were taking aspirin at the time of the PFA-100 analysis. Overall, 21 patients (33.9%) were aspirin nonresponders. The prevalence of aspirin resistance was 46.9% in the MetS group, and 20% in the control group. The difference between the two groups was statistically significant (p=0.033). Compared to aspirin responders, fasting blood glucose level was higher (102.0+/-14.6 mg/dl vs. 95.3+/-9.9 mg/dl; p=0.036) and waist circumference tended to be greater in nonresponders (97.4+/-14.1 cm vs. 89.7+/-15.0 cm; p=0.053). Multivariate logistic regression analysis showed that MetS (OR 0.28, 95% CI 0.09-0.88; p=0.029), fasting blood glucose (OR 0.95, 95% CI 0.91-0.99; p=0.045), uric acid (OR 0.46, 95% CI 0.28-0.76; p=0.002), gamma-glutamyl transferase (OR 1.04, 95% CI 1.00-1.08; p=0.043), high-sensitivity C-reactive protein (OR 1.07, 95% CI 1.01-1.12; p=0.015) levels and platelet count (OR 0.99, 95% CI 0.98-0.99; p=0.034) significantly affected aspirin resistance. Our results show that a significant proportion of MetS patients will not benefit from aspirin use due to high aspirin resistance.


DeepMesh: Mesh-based Cardiac Motion Tracking using Deep Learning.
3D motion estimation from cine cardiac magnetic resonance (CMR) images is important for the assessment of cardiac function and the diagnosis of cardiovascular diseases. Current state-of-the art methods focus on estimating dense pixel-/voxel-wise motion fields in image space, which ignores the fact that motion estimation is only relevant and useful within the anatomical objects of interest, e.g., the heart. In this work, we model the heart as a 3D mesh consisting of epi- and endocardial surfaces. We propose a novel learning framework, DeepMesh, which propagates a template heart mesh to a subject space and estimates the 3D motion of the heart mesh from CMR images for individual subjects. In DeepMesh, the heart mesh of the end-diastolic frame of an individual subject is first reconstructed from the template mesh. Mesh-based 3D motion fields with respect to the end-diastolic frame are then estimated from 2D short- and long-axis CMR images. By developing a differentiable mesh-to-image rasterizer, DeepMesh is able to leverage 2D shape information from multiple anatomical views for 3D mesh reconstruction and mesh motion estimation. The proposed method estimates vertex-wise displacement and thus maintains vertex correspondences between time frames, which is important for the quantitative assessment of cardiac function across different subjects and populations. We evaluate DeepMesh on CMR images acquired from the UK Biobank. We focus on 3D motion estimation of the left ventricle in this work. Experimental results show that the proposed method quantitatively and qualitatively outperforms other image-based and mesh-based cardiac motion tracking methods.


[Lights and shadows of combined epigenomic and transcriptomic profiling to identify novel diagnostic, prognostic or therapeutic targets for cardiovascular diseases.]
Cardiovascular diseases are the major cause of morbidity and mortality worldwide. Given the complex pathophysiology of cardiovascular diseases, an experimental approach capable of identifying multiple signaling networks activated in the heart upon pathological conditions could be particularly effective to identify new diagnostic, prognostic or therapeutic targets. Latest generation techniques now allow high-resolution investigations of the entire genome, the proteome and the cellular metabolome, as well as epigenetic modifications and associated gene expression profiles. In particular, the integration of epigenomic and transcriptomic data in the normal or pathological heart is a promising approach to identify novel molecular targets. These methods, although promising and innovative, can present several technical and analytical pitfalls. Here we will briefly describe these aspects and possible strategies to optimize the search for new diagnostic or therapeutic targets for cardiovascular diseases in the post-genomic era.


[The effect of pentobarbital sodium on mouse fibroblasts in vitro].
In mouse fibroblasts grown during a period of 48 h in a medium containing between 0.3 and 4.8 mMoles of sodium pentobarbital, there appeared diminished replication, some stathmokinesia, and plain toxicity. In further cells of this kind, taken from fetuses which had been treated with sodium pentobarbital via the dam, cell multiplication, lethality, and mitotic rate did not differ from those of control cells.


B-spline explicit active surfaces: an efficient framework for real-time 3-D region-based segmentation.
A new formulation of active contours based on explicit functions has been recently suggested. This novel framework allows real-time 3-D segmentation since it reduces the dimensionality of the segmentation problem. In this paper, we propose a B-spline formulation of this approach, which further improves the computational efficiency of the algorithm. We also show that this framework allows evolving the active contour using local region-based terms, thereby overcoming the limitations of the original method while preserving computational speed. The feasibility of real-time 3-D segmentation is demonstrated using simulated and medical data such as liver computer tomography and cardiac ultrasound images.


2010 perinatal GBS prevention guideline and resource utilization.
To quantify differences in early-onset sepsis (EOS) evaluations, evaluation-associated resource utilization, and EOS cases detected, when comparing time periods before and after the implementation of an EOS algorithm based on the Centers for Disease Control and Prevention (CDC) 2010 guidelines for prevention of perinatal Group B Streptococcus (GBS) disease. Retrospective cohort study of infants born at ≥36 weeks' gestation from 2009 to 2012 in a single tertiary care center. One 12-month period during which EOS evaluations were based on the CDC 2002 guideline was compared with a second 12-month period during which EOS evaluations were based on the CDC 2010 guideline. A cost minimization analysis was performed to determine the EOS evaluation-associated costs and resources during each time period. During the study periods, among well-appearing infants ≥36 weeks' gestation, EOS evaluations for inadequate GBS prophylaxis decreased from 32/1000 to <1/1000 live births; EOS evaluation-associated costs decreased by $6994 per 1000 live births; and EOS evaluation-associated work hours decreased by 29 per 1000 live births. We found no increase in EOS evaluations for other indications, total NICU admissions, frequency of infants evaluated for symptoms before hospital discharge, or incidence of EOS during the 2 study periods. Implementation of an EOS algorithm based on CDC 2010 GBS guidelines resulted in a 25% decrease in EOS evaluations performed among well-appearing infants ≥36 weeks' gestation, attributable to decreased evaluation of infants born in the setting of inadequate indicated GBS prophylaxis. This resulted in significant changes in EOS evaluation-associated resource expenditures.


Quick method for confirmation of quantitative trait loci.
Numerous algorithms for the identification and genetic mapping of quantitative trait loci (QTL) have been developed. Methods for confirming QTL maps involve either examination of independent segregating populations or the construction of congenic lines differing only in the QTL of interest. Because these projects require a minimum of several years or thousands of marker assessments in laboratory mice, an alternative, faster congenic method has been proposed. In a preliminary study, we tested this method for confirming QTLs identified in crosses between the ILS and ISS selected lines of mice for differential sensitivity to the hypnotic effects of ethanol. Herein, we report the construction of "segregating congenic" strains in which each QTL is made homozygous in a single generation, whereas the remainder of the genetic background is allowed to segregate. Sensitivity to ethanol among the progeny of such mice is consistent with predictions. Phenotypic variation is high, as expected, due to the background segregation, and statistical significance was attained in only 2 of 7 comparisons. Such segregating congenic populations may be a valuable research tool for confirming QTL map positions and for subsequent assessment of individual pathways and mechanisms of action of individual QTLs.


An ionising radiation-induced specific transcriptional signature of inflammation-associated genes in whole blood from radiotherapy patients: a pilot study.
This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction. Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response. Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.


Improving Translational Relevance in Preclinical Psychopharmacology (iTRIPP).
Animal models are important in preclinical psychopharmacology to study mechanisms and potential treatments for psychiatric disorders. A working group of 14 volunteers, comprising an international team of researchers from academia and industry, convened in 2021 to discuss how to improve the translational relevance and interpretation of findings from animal models that are used in preclinical psychopharmacology. The following paper distils the outcomes of the working group's discussions into 10 key considerations for the planning and reporting of behavioural studies in animal models relevant to psychiatric disorders. These form the iTRIPP guidelines (Improving Translational Relevance In Preclinical Psychopharmacology). These guidelines reflect the key considerations that the group thinks will likely have substantial impact in terms of improving the translational relevance of behavioural studies in animal models that are used to study psychiatric disorders and their treatment. They are relevant to the research community when drafting and reviewing manuscripts, presentations and grant applications. The iTRIPP guidelines are intended to complement general recommendations for planning and reporting animal studies that have been published elsewhere, by enabling researchers to fully consider the most appropriate animal model for the research purpose and to interpret their findings appropriately. This in turn will increase the clinical benefit of such research and is therefore important not only for the scientific community but also for patients and the lay public.


Synergistic effects of metal nanoparticles and a phenolic uncoupler using microdroplet-based two-dimensional approach.
A droplet-based microfluidic technique for testing multiple reagent concentrations is presented. We used this experimental approach to study combined effects of gold (AuNP) and silver nanoparticles (AgNP) with the phenolic uncoupler 2,4-dinitrophenol (DNP) with respect to the growth of Escherichia coli. In order to evaluate the toxicity of binary mixtures, we first encapsulated the E. coli cells and particle mixtures inside the microdroplets using PEEK (polyetherketone) modules. Two-dimensional concentration spaces with about 500 well separated droplets were addressed. We subsequently analyzed the cell growth, the viability and the autofluorescence intensity (metabolic activity) of the bacteria with a micro-flow-through fluorometer and photometer. Dose-dependent synergistic effects were found for the binary mixture of AgNPs and DNP, which indicated a stronger interaction in the mixture than it was expected from effect summation. For the binary mixture of DNP and AuNPs in non-toxic concentrations, we found only weak synergistic effects at low DNP concentrations. Furthermore, the non-toxic tested AuNPs causes effect summation in the binary mixture with the phenolic uncoupler. In general, we demonstrated the efficiency of a droplet-based microfluidic system for fast high-throughput screenings of binary and multiple mixtures. This work also confirmed the relevance of highly resolved droplet-based assays for the miniaturization of ecotoxicological aquatic test systems.


Striving for Stability in the Dough Mixing Quality of Spring Wheat under the Influence of Prolonged Heat and Drought.
The effects of prolonged heat and drought stress and cool growing conditions on dough mixing quality traits of spring wheat (Triticum aestivum L.) were studied in fifty-six genotypes grown in 2017 and 2018 in southern Sweden. The mixing parameters evaluated by mixograph and the gluten protein characteristics studied by size exclusion high-performance liquid chromatography (SE-HPLC) in dough were compared between the two growing seasons which were very different in length, temperature and precipitation. The genotypes varying in gluten strength between the growing seasons (≤5%, ≤12%, and ≤17%) from three groups (stable (S), moderately stable (MS), and of varying stability (VS)) were studied. The results indicate that most of the mixing parameters were more strongly impacted by the interaction between the group, genotype, and year than by their individual contribution. The excessive prolonged heat and drought did not impact the buildup and mixing time expressed as peak time and time 1-2. The gluten polymeric proteins (unextractable, %UPP; total unextractable, TOTU) and large unextractable monomeric proteins (%LUMP) were closely associated with buildup and water absorption in dough. Major significant differences were found in the dough mixing parameters between the years within each group. In Groups S and MS, the majority of genotypes showed the smallest variation in the dough mixing parameters responsible for the gluten strength and dough development between the years. The mixing parameters such as time 1-2, buildup, and peak time (which were not affected by prolonged heat and drought stress) together with the selected gluten protein parameters (%UPP, TOTU, and %LUMP) are essential components to be used in future screening of dough mixing quality in wheat in severe growing environments.


Fatty acid profile and qualitative characteristics of meat from zebu steers fed with different oilseeds.
The objective of this study was to evaluate the effects of dietary addition of ground oilseed sources on the quality, fatty acid profile, and CLA content of meat from zebu steers. Thirty-one zebu steers with an initial average age of 23 mo and an initial BW of 365 kg were used in this study. The experimental period was 84 d, which was preceded by an adaption period of 28 d. The diet was provided ad libitum with a forage:concentrate ratio of 40:60. Corn silage was used as the forage source. Four different concentrates were formulated for each treatment: without additional lipids (control) or with ground soybeans (SB), ground cottonseed (CS), or ground linseed (LS). The SB, CS, and LS diets were formulated to have 6.5% ether extract on a total dietary DM basis. The experiment was set up as a completely randomized design. After slaughter, samples were taken from the longissimus thoracis muscle for the measurement of fatty acid concentration and the evaluation of meat quality. The luminosity index was greater in the control and LS diets (P < 0.01). The greatest percentages of myristic acid (C14:0), palmitic acid (C16:0), trans octadecenoic acid (C18:1 trans-10, trans-11, or trans-12), and SFA in the subcutaneous fat were observed in the CS treatment (P < 0.01). Moreover, the least percentages of oleic acid (C18:1 cis-9) and total unsaturated fatty acids in the subcutaneous fat were observed in the CS diet (P < 0.01). The meat linoleic acid and α-linolenic acid percentages were greatest in the SB and LS treatments, respectively (P < 0.001). The unsaturated fatty acid:SFA ratio was smallest for the CS diet (P < 0.01). A gradual increase in oxidation was observed as a function of storage time; however, the diets did not affect the rancidity of the meat (P > 0.05). The fatty acid profile of subcutaneous fat was impaired by the addition of CS. Supplying ground oilseeds did not increase the content of CLA in the meat.


A Framework for Designing Scaffolds That Improve Motivation and Cognition.
A problematic, yet common, assumption among educational researchers is that when teachers provide authentic, problem-based experiences, students will automatically be engaged. Evidence indicates that this is often not the case. In this article, we discuss (a) problems with ignoring motivation in the design of learning environments, (b) problem-based learning and scaffolding as one way to help, (c) how scaffolding has strayed from what was originally equal parts motivational and cognitive support, and (d) a conceptual framework for the design of scaffolds that can enhance motivation as well as cognitive outcomes. We propose guidelines for the design of computer-based scaffolds to promote motivation and engagement while students are solving authentic problems. Remaining questions and suggestions for future research are then discussed.


Monogalactopyranosides of fluorescein and fluorescein methyl ester: synthesis, enzymatic hydrolysis by biotnylated β-galactosidase, and determination of translational diffusion coefficient.
Fluorescein monoglycosides (D-galactopyranoside (FMG) and D-glucopyranoside) and their methyl ester (MFMG) have been prepared from acetobromoglucose/galactose and fluorescein methyl ester in good yields. Enzymatic hydrolysis experiments (using biotinylated β-galactosidase) of the galacto derivatives have been performed and kinetic parameters were calculated. A 15-20 times increase of the fluorescence intensity has been observed during the hydrolysis. A linear increase of fluorescence has been noted at short time and low concentration of substrate, making these compounds useful and sensitive probes for galactosidases. The magnitude of the Michaelis-Menten constant (K(m)) value for MFMG is higher than that of FMG suggesting a possible conformational change of the fluorogenic substrate. K(m) value for biotinylated β-Gal with FMG is lower than that for the native enzyme. This observation indicates higher substrate affinity of the biotinylated enzyme in comparison to the native enzyme. Translational diffusion coefficients have been measured, for both fluorogenic substrates and both the products, employing fluorescence correlation spectroscopy. Translational diffusion coefficients for fluorogenic substrates and the enzymatic hydrolysis products have been measured to be similar, in the range of 3.5-4.5×10(-10) m(2) s(-1). Thus an enhancement or retardation of the enzymatic kinetics due to difference in translational mobility of substrate and product is not that apparent.


Complications and Outcomes of Impella Treatment in Cardiogenic Shock Patients With and Without Acute Myocardial Infarction.
Background In patients with cardiogenic shock (CS), acute myocardial infarction (AMI) is the most common cause, and a percutaneous microaxial ventricular assist device (Impella, Abiomed, Danvers, MA) is a choice for temporary mechanical circulatory support. However, data are limited on complications and outcomes of Impella treatment in patients with CS with and without AMI. Methods and Results Using nationwide prospective registry data in Japan, we included a total of 2047 patients with CS in whom the Impella devices were successfully placed between February 2020 and December 2021. Patients were divided into 2 groups according to the primary indication for the Impella use: AMI versus non-AMI. The primary end point was a composite of in-hospital all-cause death and major complications. Of the 2047 patients, the Impella was indicated for AMI in 1337 (65.3%). In the group without AMI, myocarditis was the leading cause of CS. Patients with AMI-CS were older and more likely to have cardiovascular risk factors than those with non-AMI-CS. The rates of in-hospital mortality (46.0% versus 43.9%, P=0.38) and major complications (35.2% versus 34.7%, P=0.85) were similar between the 2 groups. Overall, multivariable analysis identified older age, higher body mass index, previous transient ischemic attack or stroke, out-of-hospital cardiac arrest, and the Impella 5.0 as factors significantly associated with the primary end point. Conclusions The use of Impella in patients with and without AMI was related to similar clinical outcomes with high mortality and complication rates. Further studies are needed to identify patients who may benefit from the Impella devices in CS. Registration URL: https://www.umin.ac.jp/english. Identifier: UMIN000033603.


The emerging role of gene therapy in the treatment of cardiovascular diseases.
Cardiovascular disease is the number one source of morbidity and mortality in the United States. Therapies directed at a variety of cardiovascular diseases have blossomed over the last several decades. The advent of gene therapy, first as an intriguing tool, and subsequently with the early successes of gene trials involving the treatment of SCID, led to the development of gene therapy as a potentially exciting and viable therapy in cardiovascular diseases. A variety of novel vector technologies and delivery systems have been developed to more efficiently deliver the gene product to the desired organ or tissue bed. Early clinical trials focused on stimulating angiogenesis. Subsequently, a number of other aspects of cardiovascular disease have been identified as potential targets for gene therapy, including the prevention of restenosis, the prevention and treatment of thrombosis, and the prevention of transplant vasculopathy. With over forty clinical human trials either completed or currently enrolling, cardiovascular gene therapy has proven to be safe and initial results suggest its efficacy.