Multi-trait analysis of post-harvest storage in rocket salad (Diplotaxis tenuifolia) links sensorial, volatile and nutritional data.
Rocket salad (Diplotaxis tenuifolia; wild rocket) is an important component of ready to eat salads providing a distinct peppery flavour and containing nutritionally relevant compounds. Quality deteriorates during post-harvest, in relation to time and storage temperature amongst other factors. Volatile organic compounds (VOCs) are easily measurable from rocket leaves and may provide useful quality indicators for e.g. changes in isothiocyanates derived from nutritionally important glucosinolates. VOC profiles discriminated storage temperatures (0, 5 and 10°C) and times (over 14days). More specifically, concentrations of aldehydes and isothiocyanates decreased with time paralleling a fall in vitamin C and a reduction in sensorial quality at the two higher temperatures. Sulphur containing compounds rise at later time-points and at higher temperatures coincident with an increase in microbial titre, mirroring a further drop in sensorial quality thus indicating their contribution to off-odours.


A Clinical Comparative Study on Percutaneous and Open Approaches for Screw Internal Fixation in Treating Thoracolumbar Fractures.
Conventional open internal fixation surgery for thoracolumbar fractures has many complications and long recovery time. There are few clinical studies on the minimally invasive percutaneous injured vertebrae screw internal fixation. The purpose of this paper is to evaluate the application value of minimally invasive percutaneous injured vertebrae screw internal fixation in the treatment of thoracolumbar fractures (TF). A total of 98 patients with TF admitted to our hospital from January 2019 to December 2021 were retrospectively enrolled. According to the surgical method, the patients were divided into the study group (n = 49, treated with minimally invasive percutaneous injured vertebrae screw internal fixation) and the control group (n = 49, treated with traditional open internal fixation surgery). The two groups were compared in the perioperative period, the degree of pain at different periods, the percentage of the height of the anterior edge of the injured vertebra, the Cobb angle of the injured vertebra body and the wedge angle of the injured vertebra body at the first week and the last follow-up, and the postoperative complications and the occurrence of the cone shell after the operation were recorded. Then, statistical analysis such as Student's t test or Chi-Square test was performed. The operation time (p = 0.002), intraoperative blood loss (p < 0.001), postoperative drainage volume (p = 0.011), and length of hospital stay (p = 0.003) in the study group were significantly lower than that in the control group. The VAS in the study group (3.38 ± 1.02) was significantly lower than that in the control group (4.56 ± 1.04) on the 7th day after the operation, with a significant difference (p < 0.001). The correction values of the percentage of leading edge height (LEH), Cobb angle, wedge angle in the study group were significantly lower than that in the control group at 1 week after surgery (all ps < 0.001). The incidence of postoperative complications in the study group (one case, 2.04%) was significantly lower than that in the control group (seven cases, 14.29%) (p = 0.031). At 1 month, 6 months, 10 months, and the last follow-up, the incidence of "empty shell" on CT scan in the study group were lower than that in the control group with a significant difference (all ps < 0.05). Applying minimally invasive percutaneous injured vertebrae screw internal fixation is more beneficial to shorten the operation time and hospital stay, with fewer postoperative complications.


Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.
Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 μg kg-1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.


Neurilemmoma in the foot as a cause of heel pain: a report of two cases.
Two cases of deep-seated neurilemmoma that arose from plantar branches of the posterior tibial nerve and caused chronic heel pain are described. At the initial examination, one case was misdiagnosed as tarsal tunnel syndrome and the other was overlooked as plantar fasciitis; both cases were treated for long periods prior to operation. Deep-seated neurilemmomas in the foot can easily be overlooked and misdiagnosed as tarsal tunnel syndrome or plantar fasciitis because of the rarity, absence of palpable mass, and similarity of symptoms to those of other frequently encountered foot disorders. Magnetic resonance imaging provides the best modality for differential diagnosis. In the present cases, surgical excision of the tumors resulted in immediate and complete relief of chronic heel pain. Surgeons should consider neurilemmoma as a cause of persistent chronic heel pain despite the rarity of the disease.


Return to play post-Achilles tendon rupture: a systematic review and meta-analysis of rate and measures of return to play.
This systematic review and meta-analysis sought to identify return to play (RTP) rates following Achilles tendon rupture and evaluate what measures are used to determine RTP. A systematic review and meta-analysis were performed. Studies were assessed for risk of bias and grouped based on repeatability of their measure of RTP determination. PubMed, CINAHL, Web of Science and Scopus databases were searched to identify potentially relevant articles. Studies reporting RTP/sport/sport activity in acute, closed Achilles tendon rupture were included. 108 studies encompassing 6506 patients were included for review. 85 studies included a measure for determining RTP. The rate of RTP in all studies was 80% (95% CI 75% to 85%). Studies with measures describing determination of RTP reported lower rates than studies without metrics described, with rates being significantly different between groups (p<0.001). 80 per cent of patients returned to play following Achilles tendon rupture; however, the RTP rates are dependent on the quality of the method used to measure RTP. To further understand RTP after Achilles tendon rupture, a standardised, reliable and valid method is required.


Practices and views of wheelchair service providers regarding wheelchair-skills training for clients and their caregivers: a global online survey.
To determine the extent to which wheelchair service providers conduct wheelchair-skills training, the nature of training, and the providers' perceptions on training. Anonymous global online survey consisting of 29 questions administered via the REDCap electronic data-capture tool to English-speaking wheelchair service providers. We received 309 responses from wheelchair service providers in 35 countries. Of the respondents who responded to the question "…do you typically provide wheelchair-skills training…?" 227 (81.6%) reported "yes, always" or "yes, usually" for clients and 213 (81.9%) for caregivers. The median duration of training sessions for clients and caregivers was 45 and 30 min; the median number of sessions was 2 for both. Regarding the importance of training, 251 (94.4%) answered "very important" for clients and 201 (78.5%) for caregivers. For clients and caregivers, 182 (68.4%) and 191 (74.3%) of respondents considered themselves adequately prepared for the trainer role. A variety of barriers and facilitators to training were identified. Most wheelchair service providers report that they provide wheelchair-skills training for clients and their caregivers, most consider such training to be important and most consider themselves adequately prepared for the training role. However, the amount of training is generally minimal. Further efforts are needed to address the identified barriers to training.IMPLICATIONS FOR REHABILITATIONMost wheelchair-service providers report that they provide wheelchair-skills training.Most consider such training to be important.Most consider themselves adequately prepared.However, the extent of training is generally minimal.These findings have implications for clinicians, educators, and policymakers.


Consequences from emotional stimulus on breathing for singing.
This study aimed to investigate the effect from emotional stimulus on the correlation between intercostal (INT)/abdominal (rectus abdominis [RC], lateral abdomen [OBL], and lower lateral abdomen [LOBL]) muscle activity and trunk wall (upper thorax [UTX], lower thorax [LTX], and abdomen [ABD]) movement. An electromyographic (EMG) activity was recorded from the INT, RC, OBL, and LOBL sites. UTX, LTX, and ABD movement were traced with three strain gauge sensors. Recordings were compared between singing with emotional stimulus (ES) and without emotional stimulus (NES). Muscle activity was recorded by use of an ambulatory four-channel monitoring system (Physiometer PHY 400, Premed, Norway). Seven advanced student singers (three males and four females) participated as subjects. Four sample performances were performed: (1) extreme tones, (2) swell tones, (3) arpeggio, and (4) glissando. All sample performances were sung on the vowel /a:/. We conclude that classical singers change their breathing pattern when they vocalize using ES compared with using NES. The results imply that vocalizing using ES facilitates a more prominent role for LOBL activity in the positioning of the abdominal wall and thorax than observed when vocalizing using NES.


Characterization of cadmium removal from aqueous solution by biochar produced from a giant Miscanthus at different pyrolytic temperatures.
The objective of this study was to investigate the feasibility of biochar for removing Cd from aqueous solution. Biochars were produced from a Miscanthus sacchariflorus via slow pyrolysis at 300, 400, 500 and 600°C. Higher pyrolytic temperature resulted in biochar with a higher aromatic structure and fewer polar functional groups. In particular, pH and surface area of biochar increased greatly at pyrolytic temperatures ≥ 500°C, which increased Cd sorption capacity up to 13.24 mgg(-1). The diffuse-controlled Cd removal was likely due to a surface sorption or a precipitation reaction depending on pH. A simulation with the visual MINTEQ program indicated that the precipitate was Cd(OH)2. In addition, biochar treatment significantly removed the acute toxicity of Cd toward Daphnia magna, resulting in increase of EC50 (50% effective concentration) value from 0.16 to 0.76 mgL(-1).


Adult renal myoepithelial hamartoma.
A renal myoepithelial hamartoma presented as a lucent filling defect with gross hematuria in an adult female. Preoperative studies caused conflicting impressions. The predominance of smooth muscle and incorporated tubuloepithelial elements characterize the tumor as a hamartoma of myoepithelial type. Pertinent review of the literature confirms the rarity of this lesion in adults.


Primary and secondary gliosarcomas: clinical, molecular and survival characteristics.
Gliosarcoma is classified by the World Health Organization as a variant of glioblastoma. These tumors exhibit biphasic histologic and immunophenotypic features, reflecting both glial and mesenchymal differentiation. Gliosarcomas can be further classified into primary (de novo) tumors, and secondary gliosarcomas, which are diagnosed at recurrence after a diagnosis of glioblastoma. Using a retrospective review, patients seen at MD Anderson Cancer Center between 2004 and 2014 with a pathology-confirmed diagnosis of gliosarcoma were identified. 34 patients with a diagnosis of gliosarcoma seen at the time of initial diagnosis or at recurrence were identified (24 primary gliosarcomas (PGS), 10 secondary gliosarcomas (SGS)). Molecular analysis performed on fourteen patients revealed a high incidence of TP53 mutations and, rarely, EGFR and IDH mutations. Median overall survival (OS) for all patients was 17.5 months from the diagnosis of gliosarcoma, with a progression free survival (PFS) of 6.4 months. Comparing PGS with SGS, the median OS was 24.7 and 8.95 months, respectively (from the time of sarcomatous transformation in the case of SGS). The median OS in SGS patients from the initial diagnosis of GB was 25 months, with a PFS of 10.7 months. Molecular analysis revealed a higher than expected rate of TP53 mutations in GS patients and, typical of primary glioblastoma, IDH mutations were uncommon. Though our data shows improved outcomes for both PGS and SGS when compared to the literature, this is most likely a reflection of selection bias of patients treated on clinical trials at a quaternary center.


The hemodynamic effects and mechanism of action of pulmonary artery balloon counterpulsation in the treatment of right ventricular failure during left heart bypass.
The efficacy of pulmonary artery balloon counterpulsation (PABC) was evaluated in improving right ventricular (RV) output during left heart bypass for global cardiac failure. In 13 pigs, a 40-ml balloon was positioned within a graft anastomosed to the pulmonary artery distal to the pulmonary valve, and left heart bypass was instituted from the left atrium to the carotid artery. Global myocardial failure was produced by an infusion of propranolol (range, 25 to 78 mg). In this model, RV output decreased despite volume loading to a right atrial pressure of 15 mm Hg and atrioventricular sequential pacing at 100 beats per minute. Pulmonary artery balloon counterpulsation increased both RV output (from 519 +/- 76 to 1,117 +/- 110 ml/min; p less than 0.01) and RV systolic stroke work (from 1.3 +/- 0.4 to 2.3 +/- 0.6 gm-m; p less than 0.01). Right atrial pressure decreased (from 15.5 +/- 0.9 to 10.7 +/- 1.0 mm Hg; p less than 0.01) in 8 of the pigs studied during RV failure. In 5 pigs, ventricular fibrillation occurred without a stable model of RV failure, and there was no cardiac output before or after counterpulsation. The mechanism of action of PABC was studied by placing a flow probe around a large branch of the right pulmonary artery. During RV failure, balloon inflation caused flow through the pulmonary circulation, and ventricular systole resulted in filling of the graft. During ventricular fibrillation, balloon inflation and deflation produced only a to-and-fro movement of blood in the pulmonary artery branch without net forward flow.(ABSTRACT TRUNCATED AT 250 WORDS)


Levels of selenium in blood and tissues associated with some selenium deficiency diseases in New Zealand sheep.
Whole bloods from weaned lambs with severe selenium responsive unthriftiness usually contain <5 ng Se/ml. Mildly or moderately affected lambs have blood levels of 5-10 ng/ml. Selenium responsive infertility in ewes appears to be associated with whole blood selenium levels below 10 ng/ml.


Factors Predicting Older People's Acceptance of a Personalized Health Care Service App and the Effect of Chronic Disease: Cross-Sectional Questionnaire Study.
Mobile health (mHealth) services enable real-time measurement of information on individuals' biosignals and environmental risk factors; accordingly, research on health management using mHealth is being actively conducted. The study aims to identify the predictors of older people's intention to use mHealth in South Korea and verify whether chronic disease moderates the effect of the identified predictors on behavioral intentions. A cross-sectional questionnaire study was conducted among 500 participants aged 60 to 75 years. The research hypotheses were tested using structural equation modeling, and indirect effects were verified through bootstrapping. Bootstrapping was performed 10,000 times, and the significance of the indirect effects was confirmed through the bias-corrected percentile method. Of 477 participants, 278 (58.3%) had at least 1 chronic disease. Performance expectancy (β=.453; P=.003) and social influence (β=.693; P<.001) were significant predictors of behavioral intention. Bootstrapping results showed that facilitating conditions (β=.325; P=.006; 95% CI 0.115-0.759) were found to have a significant indirect effect on behavioral intention. Multigroup structural equation modeling testing the presence or absence of chronic disease revealed a significant difference in the path of device trust to performance expectancy (critical ratio=-2.165). Bootstrapping also confirmed that device trust (β=.122; P=.039; 95% CI 0.007-0.346) had a significant indirect effect on behavioral intention in people with chronic disease. This study, which explored the predictors of the intention to use mHealth through a web-based survey of older people, suggests similar results to those of other studies that applied the unified theory of acceptance and use of technology model to the acceptance of mHealth. Performance expectancy, social influence, and facilitating conditions were revealed as predictors of accepting mHealth. In addition, trust in a wearable device for measuring biosignals was investigated as an additional predictor in people with chronic disease. This suggests that different strategies are needed, depending on the characteristics of users.


Tolerance to sound intensity of binaural coincidence detection in the nucleus laminaris of the owl.
Neurons of the owl's nucleus laminaris serve as coincidence detectors for measurement of interaural time difference. The discharge rate of nucleus laminaris neurons for both monaural and binaural stimulation increased with sound intensity until they reached an asymptote. Intense sounds affected neither the ratio between binaural and monaural responses nor the interaural time difference for which nucleus laminaris neurons were selective. Theoretical analysis showed that high afferent discharge rates cause coincidence detectors with only excitatory input to lose their selectivity for interaural time difference when coincidence of impulses from the same side becomes as likely as that of impulses from the two sides. We hypothesize that inhibitory input whose strength increases with sound intensity protects nucleus laminaris neurons from losing their sensitivity to interaural time difference with intense sounds.


Engaging children and young people on the potential role of artificial intelligence in medicine.
There is increasing interest in Artificial Intelligence (AI) and its application to medicine. Perceptions of AI are less well-known, notably amongst children and young people (CYP). This workshop investigates attitudes towards AI and its future applications in medicine and healthcare at a specialised paediatric hospital using practical design scenarios. Twenty-one members of a Young Persons Advisory Group for research contributed to an engagement workshop to ascertain potential opportunities, apprehensions, and priorities. When presented as a selection of practical design scenarios, we found that CYP were more open to some applications of AI in healthcare than others. Human-centeredness, governance and trust emerged as early themes, with empathy and safety considered as important when introducing AI to healthcare. Educational workshops with practical examples using AI to help, but not replace humans were suggested to address issues, build trust, and effectively communicate about AI. Whilst policy guidelines acknowledge the need to include children and young people to develop AI, this requires an enabling environment for human-centred AI involving children and young people with lived experiences of healthcare. Future research should focus on building consensus on enablers for an intelligent healthcare system designed for the next generation, which fundamentally, allows co-creation. Children and young people (CYP) want to be included to share their insights about the development of research on the potential role of Artificial Intelligence (AI) in medicine and healthcare and are more open to some applications of AI than others. Whilst it is acknowledged that a research gap on involving and engaging CYP in developing AI policies exists, there is little in the way of pragmatic and practical guidance for healthcare staff on this topic. This requires research on enabling environments for ongoing digital cooperation to identify and prioritise unmet needs in the application and development of AI.


Bone marrow mononuclear stem cells transplanted in rat infarct myocardium improved the electrical conduction without evidence of proarrhythmic effects.
The arrhythmogenic effect of stem cells transplantation (SCT) in an infarct myocardium is still unknown. We investigated arrhythmogenicity of SCT in rat cryo-infarct model. In rat cryo-infarct model, bone marrow mononuclear stem cells (MNSC, 1 x 10(7) cells) were transplanted into the infarct border zone (BZ) of the LV epicardium. We compared the optical mapping and inducibility of ventricular tachycardia/fibrillation (VT/VF) among normal (n=5), cryo-infarct (n=6), and SCT rats (n=6). The VT/VF inducibility was higher in the cryo- infarct (47.2%, p=0.001) and SCT groups (34.6%, p=0.01) than in the normal group (12.8%). The induced VT/VF episodes persisted for more than 2 minutes in 4.3%, 26.4% and 17.3% in the normal, cryo-infarct and SCT group, respectively. In the SCT group, the action potential duration at 70% was shorter at the SCT site than the BZ during SR (75.2 +/- 8.1 vs. 145.6 +/- 4.4 ms, p=0.001) and VT (78.2 +/- 13.0 vs. 125.7 +/- 21.0 ms, p= 0.001). Conduction block was observed at the SCT site and BZ during VT. However, no reentry or ectopic foci were observed around the SCT sites. The electrical conduction was improved by SCT without evidence of augmentation of arrhythmia in the rat cryo-infarct model.


Electrophoresis in gel slabs of any thickness: a rapid, multiple, adaptable, facile and inexpensive method.
A new apparatus has been developed to facilitate a good, effective transfer of protein from a first-dimension gel into a second-dimension gel. This new simple apparatus makes running time of the slab gel short and is convenient for the simultaneous processing of many polyacrylamide gel slabs and ultra-thin (100 micrometers) gels. Many gels can be run at the same time in a small space and be readily inserted or removed. Multiple gels can easily be prepared. The plates can have any desired shape and dimension, and their thickness can easily be changed. The present method is very simple and inexpensive, has a wide application and has many other advantages.


[The antiradiation effect of the cytostatic ribamidil and the possible mechanisms of its action].
Ribamidil has a cytostatic effect on bone marrow cells and a radioprotective therapeutic action. Ribamidil favors CFUs proliferation and does not interfere with the process of CFUs migration.


Calcium silicate layer on titanium fabricated by electrospray deposition.
Titanium and its alloys have been used as implant materials. Non-ideal osseointegration of the implant materials has facilitated the development of the bioactive coatings on the implant surfaces. In this work, the bioactive calcium silicate (CaSi) powder prepared in a green synthesis route was used to cover the surface of Ti implants by a facile electrospray deposition method. Post annealing in air was also applied to form the oxidation layer on the Ti surface with the aim of increasing the bond strength between the CaSi coating layer and Ti substrate. For the characterization of the coatings several analytical methods such as X-ray diffraction, scanning electron microscopy, secondary neutral mass spectrometry, and Raman-spectroscopy were used, in addition to the measurement of bond strength and corrosion resistance. The results indicated a uniform CaSi layer with a thickness of about 1 μm deposited on the Ti substrate. Annealing in the range of 700-900 °C in air resulted in the formation of rutile phase of TiO2; more importantly, annealing at 800 °C did not significantly affect the composition of the CaSi layer consisting of β-Ca2SiO4. The bond strength between the coating layer and Ti substrate can be remarkably enhanced at an annealing temperature of 700 or 800 °C compared with the as-prepared coating without annealing. The annealed coatings had a better corrosion resistance than the as-prepared coating. It is concluded that the electrospray method associated with the post-annealing can be successfully used for the deposition of a CaSi layer with a defined structure and composition on titanium implants.


Comparative assessment of oral hygiene and periodontal status among children who have Poliomyelitis at Udaipur city, Rajasthan, India.
To assess and compare the oral hygiene and periodontal status among children with Poliomyelitis having upper limb disability, lower limb disability and both upper and lower disability at Udaipur city, Rajasthan, India. Total sample comprised of 344 Poliomyelitis children (upper limb disability: 33.4%; lower limb disability: 33.7%; both upper and lower limb disability: 32.9%) in the age group of 12-15 years. Clinical examination included recording Simplified Oral Hygiene Index and Community Periodontal Index. Analysis of variance (ANOVA), multiple logistic and stepwise linear regression were used for statistical analysis. The mean OHI-S (2.52 ± 1.05) score was found to be highest among children who had both upper and lower limb disability (p<0.05). The highest and lowest mean number of healthy sextants were found among those with only lower limb disability (4.53 ± 2.05) and among those with both upper and lower limb disability (0.77 ± 1.39), respectively (p<0.05). Stepwise multiple linear and multiple logistic regression analysis showed that the best predictor for oral hygiene and periodontal status was limb involved in the disability. The results of the study depicted an overall poor oral hygiene and periodontal status of the group. It was recognized that limbs involved in the disability had an impact on the oral hygiene and periodontal condition. The situation in this specialized population draws immediate attention for an integrated approach in improving the oral health and focus towards extensive research.


Family history and frontal lobe seizures predict long-term remission in newly diagnosed cryptogenic focal epilepsy.
Cryptogenic focal epilepsy (CFE) is a heterogeneous clinical disorder including patients with severe refractory forms and patients with a fairly good prognosis. Predictors of prognosis in CFE are poorly understood. The aim of this retrospective study is to identify long-term (5-year) prognostic predictors in patients with newly diagnosed CFE. Subjects with cryptogenic focal epilepsy (CFE) seen from April 1987 to September 2011 in two twin Epilepsy Centres located in Reggio Calabria and Catanzaro, Calabria, Southern Italy, were screened. Patients were excluded if they had psychogenic seizures, major psychiatric disorders presence of brain lesions except for non-specific white matter T2-hyperintensities, short follow-up (less than five years) or for having received the diagnosis of CFE elsewhere. One hundred and eighty-six patients, firstly diagnosed in our Centres, constituted the study sample. Survival curves were generated according to the Kaplan-Meier method and compared with the log-rank test. The endpoint was the cumulative time-dependent chance of 5-year remission after treatment start. Independent predictors of remission were tested by multivariate analysis using Cox proportional hazards function models. The accuracy of the resulting model was tested with Receiver Operating Characteristics (ROC) curve analysis. The cumulative incidence of remission was 23%. At Kaplan-Meier analysis, the only factor predicting remission was family history of epilepsy or febrile seizures (FS; p=0.02). At Cox regression, family history and frontal lobe epilepsy showed to be independent predictors of outcome (p=0.02 and 0.03, respectively). The accuracy of these predictors was good (area under ROC curve 0.648, 95% CI 0.575-0.716). Interestingly, we also found a considerable (7 years) diagnostic delay that did not result in a worse prognosis. About one quarter of subjects with newly diagnosed CFE attains 5-year seizure remission during follow-up. Family history of epilepsy or FS and frontal localization are independent prognostic predictors.


Enzymic hydrolysis of diol lipids by pancreatic lipase.
Chain length and positional specificities of pancreatic lipase for diol lipids have been examined by use of the synthetic substrates such as the diol esters and related esters that contain C6--C20 even-numbered saturated acids and oleic acid as fatty acids, and ethylene glycol, 1,2- and 1,3-propanediols, 1,3-, 1,4-, and 2,3-butanediols, monohydric alcohols, and glycerol as alcohols. No remarkable difference in the degree of hydrolysis was observed in the case of diol esters having C14--C20 fatty acids at least during 30-min digestion, though hydrolysis reached a maximum in diol diotanoates after the same period. Pancreatic lipase specifically released only the fatty acids esterified with the primary hydroxyl groups of diols.


The clinical pharmacokinetics of quinapril.
Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose proportional following single oral 2.5- to 80-mg Q doses. Q absorption and hydrolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL following 40-mg Q). Dose-proportional QT area under the curve and dose-independent percent of dose excreted in urine as QT demonstrate that the extent of Q conversion to QT is constant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clearances of 1,850 and 220 mL/min, respectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactivity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketopiperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an administered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary excretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clearance of both Q and QT is independent of dose, and metabolism to compounds other than QT is not extensive.


ERK phosphorylation is dependent on cell adhesion in a subset of pediatric sarcoma cell lines.
Osteosarcoma (OS) and Pax-Foxo1 fusion negative rhabdomyosarcoma (FN-RMS) are pediatric sarcomas with poor prognoses in patients with advanced disease. In both malignancies, an actin binding protein has been linked to poor prognosis. Integrin adhesion complexes (IACs) are closely coupled to actin networks and IAC-mediated signaling has been implicated in the progression of carcinomas. However, the relationship of IACs and actin cytoskeleton remodeling with cell signaling is understudied in pediatric sarcomas. Here, we tested the hypothesis that IAC dynamics affect ERK activation in OS and FN-RMS cell lines. Adhesion dependence of ERK activation differed among the OS and FN-RMS cells examined. In the OS cell lines, adhesion did not have a consistent effect on phospho-ERK (pERK). ERK phosphorylation in response to fetal calf serum or 1 ng/ml EGF was nearly as efficient in OS cell lines and one FN-RMS cell line in suspension as cells adherent to poly-l-lysine (PL) or fibronectin (FN). By contrast, adhesion to plastic, PL or FN increased ERK phosphorylation and was greater than additive with a 15 min exposure to 1 ng/ml EGF in three FN-RMS cell lines. Increases in pERK were partly dependent on FAK and PAK1/2 but independent of IAC maturation. As far as we are aware, this examination of adhesion-dependent signaling is the first in pediatric sarcomas and has led to the discovery of differences from the prevailing paradigms and differences in the degree of coupling between components in the signaling pathways among the cell lines.


Hypertrophic pachymeningitis in polyarteritis nodosa: a case-based review.
Hypertrophic pachymeningitis (HP) is a rare neurological disorder with focal or diffuse thickening of the dura mater, which usually causes headache, cranial neuropathies, seizures, and motor or sensory impairments. The development of HP is attributed to an immune-mediated mechanism, and some autoimmune diseases have been implicated in the development of HP. Herein, we describe the case of a 73-year-old woman with persistent headache ascribable to HP, which developed approximately 3 years after a diagnosis of polyarteritis nodosa (PAN). She was treated with high-dose corticosteroid and cyclophosphamide that resulted in immediate disappearance of headache and improved radiological findings of thickened dura mater. In addition, she was subsequently administered methotrexate, ultimately resulting in maintenance of remission and regular reduction of prednisolone. In our review of published English articles, only two cases of HP in patients with PAN have been reported to date, suggesting that HP is a rare complication in PAN. However, it should be recognized that HP may develop as a neurological involvement related to PAN.


Gastrin's trophic effect in the colon: identification of a signaling pathway mediated by protein kinase C.
In previous studies we have reported that gastrin exerts a trophic effect on rat colonic epithelial cells in vitro. The effect of gastrin appeared to be mediated through a protein kinase C mechanism. In this study, we have characterized the role of protein kinase C in the gastrin-induced stimulation. Gastrin, in a time- and dose-dependent manner, increased protein kinase C translocation from the cytosol to the membrane, an index of enzyme activation. Maximum translocation occurred in 1 to 2 min following exposure to gastrin (10(-8) M), before declining back to baseline level within 5 min. Gastrin did not change total protein kinase C activity in the colonic cells. Staurosporine, an inhibitor of protein kinase C, totally abolished the basal as well as the gastrin-stimulated activity of protein kinase C. The tumor promoter phorbol 12-myristate 13-acetate also stimulated colonic epithelial protein kinase C. However, prolonged treatment of cells with phorbol inhibited their subsequent response to gastrin stimulation. The response to gastrin was also prevented by the gastrin receptor antagonist proglumide. These observations suggest that protein kinase C mediates the stimulatory effect of gastrin on colonic epithelial cells, possibly through a receptor mechanism.


Changes of trans and saturated fatty acid content in savory baked goods from 2015 to 2021 and their effect on consumers' intake using substitution models: A study conducted in Greece.
In Greece, nearly a third of savory baked goods (SBGs) exceeded the limit of 2 g of nonruminant or industrial trans fatty acids (i-TFA) per 100 g fat in 2015. The impact of the Commission Regulation (European Union) 2019/649 on exposure to trans fatty acids (TFA), i-TFA, and saturated fatty acid (SFA) from SBGs has not been previously evaluated. The study aimed to explore fatty acid reformulation of SBG products and assess differences in TFA, i-TFA, and SFA intakes using a sample of Greek SBG consumers from a nationally representative survey. In 2021, 140 samples of SBGs were collected in the greater metropolitan area of Athens, and their fat profile and content were compared to those from 2015. Based on these measurements, food consumption substitution models were employed to examine TFA and SFA intake differences, and the percent contribution from SBG among consumers was calculated (N = 1008). Nutrient densities were calculated by adjusting all fat intakes by individual mean energy intake (percentage of daily total energy intake). The 2% i-TFA legislative limit/100 g of fat in measured SBGs was exceeded by 11.4% in 2021 compared to 31.1% in 2015 (19.7% increase in compliance). Median i-TFA and TFA intakes from SBGs were reduced from 0.05 (0.01, 0.12)% and 0.13 (0.03, 0.27)% in 2015 to 0.03 (0.01, 0.09) and 0.06 (0.03, 0.13)% in 2021, respectively. In terms of SFA, a mean increase/100 g was calculated, resulting in an increased intake in 2021 compared to 2015 [5.18% (2.78, 8.37) and 3.55 (1.99, 5.73), respectively]. Despite the reductions seen in i-TFA content of SBGs, food product reformulation efforts in Greece should focus not only on TFA content but also on SFA reduction to improve public health.


[Systemic diseases in patients with cataract-extraction (author's transl)].
214 patients who underwent cataract-extraction in 1973 were examined for systemic diseases. The average age of patients with (70%) and without (30%) general diseases was 67 years. The frequency of cardio-vascular and respiratory diseases corresponded to that observed in the general population of the same age. In contrast, the rate of diabetes mellitus was four times higher than to be expected statistically. The importance of an adequate clinical management of diabetic cataract patients is discussed.


Altering the orientation of a fused protein to the RNA-binding ribosomal protein L7Ae and its derivatives through circular permutation.
RNA-protein complexes (RNPs) are useful for constructing functional nano-objects because a variety of functional proteins can be displayed on a designed RNA scaffold. Here, we report circular permutations of an RNA-binding protein L7Ae based on the three-dimensional structure information to alter the orientation of the displayed proteins on the RNA scaffold. An electrophoretic mobility shift assay and atomic force microscopy (AFM) analysis revealed that most of the designed circular permutants formed an RNP nano-object. Moreover, the alteration of the enhanced green fluorescent protein (EGFP) orientation was confirmed with AFM by employing EGFP on the L7Ae permutant on the RNA. The results demonstrate that targeted fine-tuning of the stereo-specific fixation of a protein on a protein-binding RNA is feasible by using the circular permutation technique.


Fatal Abdominal Compartment Syndrome Due to Severe Triglyceride-Induced Pancreatitis in Early Pregnancy.
Serum levels of maternal lipids rise physiologically in normal pregnancy, and women with underlying hypertriglyceridemia may experience dramatic elevations which place them at risk for pancreatitis. We describe the case of a woman with severe familial hypertriglyceridemia and prior pancreatitis who discontinued her lipid-lowering therapy early in pregnancy. She promptly developed severe abdominal pain and was hospitalized with acute pancreatitis during the late first trimester. Despite aggressive medical treatment and critical care monitoring, she developed abdominal compartment syndrome (ACS) with associated acute renal failure, which progressed to cardiorespiratory failure and was ultimately fatal. ACS is an alarming complication of acute pancreatitis that has been poorly studied in pregnancy.


Functional domains of the insulin receptor responsible for chemotactic signaling.
The insulin receptor mediates a variety of cellular responses to insulin, including glucose transport, endocytosis, and cell proliferation. The role of the insulin receptor in mediating cellular motility has not, however, been extensively investigated. In this report, we demonstrate that chinese hamster ovary (CHO) cells that normally have low concentrations of insulin receptor display chemotaxis toward insulin after overexpression of the wild type human insulin receptor. Chemotaxis toward insulin proceeded through a pertussis toxin-sensitive pathway and required both tyrosine kinase activity and tyrosine autophosphorylation of the regulatory region of the beta-subunit. In contrast, the autophosphorylation sites in the carboxyl terminus of the receptor were not required for chemotactic activity. A mutation in the juxtamembrane region, which disabled tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), also prevented the chemotactic response, suggesting a possible role for IRS-1 in chemotactic signaling. In the absence of insulin receptor, however, the presence of excess transfected IRS-1 was not sufficient to mediate chemotaxis toward insulin. These results demonstrate that the intact insulin receptor can stimulate a chemotactic signaling pathway and that this initial pathway more closely correlates with that for insulin-stimulated cell proliferation than for insulin-stimulated receptor endocytosis.


Rapid cycling of nitrogen and phosphorus from dying roots of Lolium perenne.
Previous experiments, using 32P pulse labelling, showed that when roots of Lolium perenne were detached from the shoot, a substantial proportion of the phosphorus in the roots could within a few weeks be released and be captured by another, living plant. This paper describes experiments designed to confirm and further investigate this rapid nutrient transfer. Roots from plants grown with ample N and P were detached and placed in litter bags in soil. They lost up to 60% of their initial N and up to 70% of their P in three weeks. Even when roots were grown with deficient P supply, resulting in C:P ratios of 300-400, they lost 20-30% of their initial P. Time-courses of 32P loss from roots suspended in solution gave results which agreed with these figures. The initially rapid rate of 32P loss had declined greatly within three weeks. In a pot experiment small L. perenne plants showed a marked increase in their N and P content during 30 days after a neighbouring large plant's shoot was removed, supporting rapid capture of nutrients lost from the detached roots. To investigate P loss from roots while attached to the shoot, L. perenne shoots were clipped every four days and 32P loss from the roots measured. After the third clip the rate of loss increased, eventually to more than four times that from the control plants.


High-efficiency polymer solar cells with small photon energy loss.
A crucial issue facing polymer-based solar cells is how to manage the energetics of the polymer/fullerene blends to maximize short-circuit current density and open-circuit voltage at the same time and thus the power conversion efficiency. Here we demonstrate that the use of a naphthobisoxadiazole-based polymer with a narrow bandgap of 1.52 eV leads to high open-circuit voltages of approximately 1 V and high-power conversion efficiencies of ∼9% in solar cells, resulting in photon energy loss as small as ∼0.5 eV, which is much smaller than that of typical polymer systems (0.7-1.0 eV). This is ascribed to the high external quantum efficiency for the systems with a very small energy offset for charge separation. These unconventional features of the present polymer system will inspire the field of polymer-based solar cells towards further improvement of power conversion efficiencies with both high short-circuit current density and open-circuit voltage.


Climate change mitigation role of renewable energy consumption: Does institutional quality matter in the case of reducing Africa's carbon dioxide emissions?
Renewable energy and institutions have emerged among other variables touted to address climate change problems. However, empirical results have been conflicting. With a relatively poorer state of institutional quality and a lower level of renewable energy development amidst rising carbon dioxide (CO2) emissions in Africa, the study assesses: a) the direct effect of renewable energy and institutional quality on CO2 emissions in Africa; and b) the moderation role of institutional quality on the effect of renewable energy on CO2 emissions in Africa. The study relies on panel data covering 2002-2021 for 32 African countries. The Fully-Modified OLS regression method is employed to analyze the data based on the environmental Kuznets curve (EKC) hypothesis and Stochastic Impacts by Regression on Population, Affluence, & Technology (STIRPAT) model. The results show that urbanization and trade openness increase CO2 emissions. Although income has a positive effect on carbon emissions, the square term has a negative confirming the EKC hypothesis. Renewable energy also reduces CO2 emissions. Institutional quality variables of control of corruption, rule of law, regulatory quality, political stability and absence of violence, voice and accountability, government effectiveness and institutional index created from the above indicators reduce CO2 emissions. In addition, except government effectiveness, the remaining indicators of institutional quality negatively moderate the effect of renewable energy on CO2 emissions. The results among other things imply that intensifying the development and usage of renewable energy would help address the rising carbon dioxide emissions trend in Africa. Also, strengthening institutions promises to reduce CO2 emissions.


Thalidomide inhibition of perturbed vasculature and glial-derived tumor necrosis factor-alpha in an animal model of inflamed Alzheimer's disease brain.
Injection of Abeta(1-42) peptide into rat hippocampus has been found to induce microglial reactivity and perturbed vasculature in an animal model of inflamed Alzheimer's disease (AD) brain. We report the anti-angiogenic and anti-inflammatory compound, thalidomide, to significantly inhibit peptide-induced vascular changes including endothelial cell proliferation (marker rat endothelial cell antigen-1, RECA-1), angiogenic activity (marker laminin) and leakiness of blood-brain barrier (BBB, marker albumin). Thalidomide also blocked microgliosis and astrogliosis with double immunostaining showing considerable regions of association of activated microglia with vascular remodeling and leaky BBB. Thalidomide inhibition of the glial-derived proinflammatory/angiogenic factor TNF-alpha (tumor necrosis factor-alpha) in Abeta(1-42)-injected brain and also in vitro from peptide-activated human microglia could underly the changes in vascular processes. Thalidomide treatment in vivo was also associated with a significant reduction in hippocampal neuronal loss. Our findings suggest altered cerebral vasculature as an integral component of inflammatory responses with thalidomide an effective inhibitor of gliosis, vascular changes and TNF-alpha leading to neuroprotection in an animal model of inflamed AD brain.


An integrated leachate bed reactor - anaerobic membrane bioreactor system (LBR-AnMBR) for food waste stabilization and biogas recovery.
This study developed an integrated LBR - AnMBR system for efficient stabilization and biogas recovery from food waste (FW) at room temperatures (21-22 °C). First, the leachate recirculation rate (4.4-13.2 L/h) was optimized to maximize hydrolysis and acidification yields. The maximum hydrolysis yield of 551 gSCOD/kg VSadded was achieved at recirculation rate of 13.2 L/h. The VFA concentrations in the FW leachate was as high as 12.5-16.0 g/L, resulting in a high acidification of 468 g CODVFA/kg VS. The solubilized FW was further stabilized by feeding the leachate to AnMBR. Different hydraulic (HRT) and solids retention times (SRT) were tested to achieve high COD removal and methane yields. High COD removal of 86 ± 3% was obtained in the AnMBR at HRT of 13 and SRT of 75 days. High biogas recovery of about 850 kWh per ton FWtreated was achieved along with high quality of AnMBR permeates containing low COD concentration but advantageously high concentration of nutrients (NH4+-N 317-403 mg/L, total phosphate 23-213 mg/L) without any particulates, which can be reused for landscape or liquid fertilizer.


Characterizing Orthostatic Tremor Using a Smartphone Application.
Orthostatic tremor is one of the few tremor conditions requiring an electromyogram for definitive diagnosis since leg tremor might not be visible to the naked eye. An iOS application (iSeismometer, ObjectGraph LLC, New York) using an Apple iPhone 5 (Cupertino, CA, USA) inserted into the patient's sock detected a tremor with a frequency of 16.4 Hz on both legs. The rapid and straightforward accelerometer-based recordings accomplished in this patient demonstrate the ease with which quantitative analysis of orthostatic tremor can be conducted and, importantly, demonstrates the potential application of this approach in the assessment of any lower limb tremor.


Enzymatic hydrolysis of haloperidol decanoate and its inhibition by proteins.
When [14C]haloperidol decanoate, a long-acting neuroleptic and an ester of haloperidol and decanoic acid, was incubated in human whole blood and plasma and in rat plasma and homogenates of rat brain, lung, liver, kidney, pancreas and muscle, no hydrolysis of the ester was seen. Although the decanoate was hydrolyzed by partially purified carboxylesterase, addition of rat plasma or liver homogenate to the enzymic reaction mixture resulted in marked inhibition of hydrolysis, whereas addition of the defatted residues of plasma or liver produced only partial inhibition. The enzymic hydrolysis was inhibited also by beta-lipoprotein and albumin, depending on their concentrations. The assumption that interaction between haloperidol decanoate and protein resulted in inhibition of the hydrolytic reaction mediated by the enzyme was validated by kinetic models and experimental data. The kinetics were apparently competitive. Based on the kinetic analysis, the interaction between the decanoate and albumin or beta-lipoprotein was investigated by measuring their equilibrium constants and extent of protein binding. Haloperidol decanoate appeared to interact with several proteins; this was exemplified by other measures of protein binding, an increasing effect of proteins on the solubility, and the partition ratio of the ester. The interaction between haloperidol decanoate and proteins caused marked stabilization of this ester against enzymatic hydrolysis and, thereby, influenced its metabolism.


Home-based treadmill training to improve gait performance in persons with a chronic transfemoral amputation.
To investigate the effectiveness of a home-based multiple-speed treadmill training program to improve gait performance in persons with a transfemoral amputation (TFA). Repeated measures. Research laboratory. Individuals with a TFA (N=8) who had undergone a unilateral amputation at least 3 years prior as a result of limb trauma or cancer. Home-based treadmill walking for a total of 30 minutes a day, 3 days per week for 8 weeks. Each 30-minute training session involved 5 cycles of walking for 2 minutes at 3 speeds. Participants were tested pretraining and after 4 and 8 weeks of training. The primary measures were temporal-spatial gait performance (symmetry ratios for stance phase duration and step length), physiological gait performance (energy expenditure and energy cost), and functional gait performance (self-selected walking speed [SSWS], maximum walking speed [MWS], and 2-minute walk test [2MWT]). Eight weeks of home-based training improved temporal-spatial gait symmetry at SSWS but not at MWS. A relative interlimb increase in stance duration for the prosthetic limb and proportionally greater increases in step length for the limb taking shorter steps produced the improved symmetry. The training effect was significant for the step length symmetry ratio within the first 4 weeks of the program. Energy expenditure decreased progressively during the training with nearly 10% improvement observed across the range of walking speeds. SSWS, MWS, and 2MWT all increased by 16% to 20%. Home-based treadmill walking is an effective method to improve gait performance in persons with TFA. The results support the application of training interventions beyond the initial rehabilitation phase, even in individuals considered highly functional.


Evaluation of human T-cell leukemia virus in vitro diagnostics using plasma specimens collected in Japan.
In vitro diagnostics (IVDs) for primary detection test/screening of human T-cell leukemia virus (HTLV) have recently been updated to new-generation products in Japan. In this study, the performance of these products was evaluated and discussed in terms of the usability of HTLV diagnosis in Japan. The performance of 10 HTLV IVDs for primary detection test and confirmatory/discriminatory test was evaluated. Plasma specimens that had been declared ineligible for transfusion were provided by the Japanese Red Cross Blood Center. The diagnostic specificity of the IVDs was 100% (160/160). Six sandwich assays resulted in all HTLV-1/HTLV-positive specimens being positive (46/46). On the other hand, one sandwich assay, IVD under development 2 (UD2), resulted in one HTLV-1-positive and one HTLV-positive specimen being negative (44/46, 95.7%). One indirect assay, HISCL HTLV-1, could not detect one HTLV-positive specimen (45/46, 97.8%), but the updated product, UD1, correctly detected it (46/46, 100%). Serodia HTLV-I, based on a particle agglutination assay, resulted in 44 of the 46 positive specimens, but could not detect two specimens (44/46, 95.7%). ESPLINE HTLV-I/II, based on an immunochromatography assay (ICA), was able to diagnose all specimens as positive (46/46, 100%). Six sandwich assays and an ICA demonstrated high diagnostic sensitivity and specificity and are recommended for use in HTLV diagnosis in conjunction with confirmatory/discriminatory test using the INNO-LIA HTLV-I/II Score.


The relationship between lifespan and reproduction in the grasshopper Melanoplus.
An experiment was conducted to examine the relationship between reproduction and longevity in an annual iteroparous species of grasshopper, Melanoplus sanguinipes. Two hypotheses derived from life history theory were tested. These included: 1) virgin females produce fewer eggs and live longer than mated females, and 2) the rate of egg production and longevity are negatively related. The results of this study indicated that there is no trade-off between reproduction and longevity in this species of grasshopper. It is suggested that other factors, such as male-female interactions, may be more important in affecting female survival than reproduction.


Induction of parturition in Zebu-cross recipients carrying in vitro-produced Bos indicus embryos.
Induction of parturition has been used as a management tool in cattle in several countries, but not commonly in Zebu breeds in tropical production systems. When timed according to the stage of gestation, most induction protocols employing a combination of PGF2alpha and a potent, short-acting corticosteroid, resulted in a predictable interval from induction to calving, with no detrimental effects on calf viability; however, the incidence of placental retention was usually elevated. Pretreatment with a long-acting corticosteroid induced placental maturation and greatly reduced the incidence of placental retention following induction with PGF2alpha and a short-acting corticosteroid. Recently, Brazilian cattle breeders have faced a new challenge with a large number of in vitro-produced embryos. Without a reliable method of cryopreservation, large numbers of embryos have been transferred fresh, creating a new demand for protocols for synchronizing recipients and managing their calving. A parturition-induction protocol, efficacious in Bos taurus cattle, was modified for use in Bos indicus cattle (which generally have a longer gestation than B. taurus cattle). Zebu-cross recipients carrying Nelore in vitro-produced embryos were pretreated with 1 mg/60 kg triamcinolone acetonide on Day 280 of gestation, followed by treatment with 500 microg of cloprostenol and 25 mg of dexamethasone on Day 287. The interval from treatment to calving was predictable and the incidence of retained placenta was low, similar to that described previously for B. taurus cattle, demonstrating that this treatment protocol could be used for induction of parturition in Zebu cattle in Brazil.


Changes in the excitability of hindlimb motoneurons during muscular atonia induced by stimulating the pedunculopontine tegmental nucleus in cats.
We have previously reported that electrical stimulation delivered to the ventral part of the pedunculopontine tegmental nucleus (PPN) produced postural atonia in acutely decerebrated cats [Neuroscience 119 (2003) 293]. The present study was designed to elucidate synaptic mechanisms acting on motoneurons during postural atonia induced by PPN stimulation. Intracellular recording was performed from 72 hindlimb motoneurons innervating extensor and flexor muscles, and the changes in excitability of the motoneurons following the PPN stimulation were examined. Repetitive electrical stimulation (20-50 microA, 50 Hz, 5-10 s) of the PPN hyperpolarized the membrane potentials of both the extensor and flexor motoneurons by 2.0-12 mV (6.0 +/- 2.3 mV, n = 72). The membrane hyperpolarization persisted for 10-20 s even after termination of the stimulation. During the PPN stimulation, the membrane hyperpolarization was associated with decreases in the firing capability (n = 28) and input resistance (28.5 +/- 6.7%, n = 14) of the motoneurons. Moreover the amplitude of Ia excitatory postsynaptic potentials was also reduced (44.1 +/- 13.4%, n = 14). After the PPN stimulation, these parameters immediately returned despite that the membrane hyperpolarization persisted. Iontophoretic injections of chloride ions into the motoneurons reversed the polarity of the membrane hyperpolarization during the PPN stimulation. The polarity of the outlasting hyperpolarization however was not reversed. These findings suggest that a postsynaptic inhibitory mechanism, which was mediated by chloride ions, was acting on hindlimb motoneurons during PPN-induced postural atonia. However the outlasting motoneuron hyperpolarization was not due to the postsynaptic inhibition but it could be due to a decrease in the activity of descending excitatory systems. The functional role of the PPN in the regulation of postural muscle tone is discussed with respect to the control of behavioral states of animals.


Relationship between an increase of juvenile hormone titer in early instars and the induction of diapause in fully grown larvae of Sesamia nonagrioides.
The larvae of Sesamia nonagrioides (Lepidoptera: Noctuidae) grown at 25 degrees C and long photoperiod (16:8h light:dark) pupate in the 5th or 6th (mostly) larval instar, while the larvae reared under a short photoperiod (12:12h) enter diapause during which they consume some food and undergo up to 12 (usually 3-4) stationary larval molts. Diapause programming includes an increase of juvenile hormone (JH) titer in the hemolymph from about 20 to 50 nM in the 4th and 5th instar larvae (titer in earlier instars was not measured). JH I, II, and III are present in approximate ratio 1-2:10:1. The JH titer drops to zero before pupation but remains around 20 nM during diapause. Perfect extra larval molts associated with a body weight increase can be induced in the non-diapausing larvae with a JH analogue (JHA). The weight rise is due to accumulation of reserves and not to a general body growth. The timing of extra molts is similar to the molting pattern of the diapausing larvae only when JHA is present since early larval instars. In the diapausing larvae, JHA application affects neither molting periodicity nor the body weight. It is concluded that (1) Increased JH titer in early larval instars is a part of diapause programming; (2) The extension of larval stage in the diapausing larvae, but not the timing pattern of extra molts, is due to continuously high JH titer; (3) The diapause program includes low food intake, maintenance of a certain body weight, and periodic larval molts.


Distinct role of subcomplexes of the COPI coat in the regulation of ArfGAP2 activity.
COPI vesicles serve for transport of proteins and membrane lipids in the early secretory pathway. Their coat protein (coatomer) is a heptameric complex that is recruited to the Golgi by the small GTPase Arf1. Although recruited en bloc, coatomer can be viewed as a stable assembly of an adaptin-like tetrameric subcomplex (CM4) and a trimeric 'cage' subcomplex (CM3). Following recruitment, coatomer stimulates ArfGAP-dependent GTP hydrolysis on Arf1. Here, we employed recombinant coatomer subcomplexes to study the role of coatomer components in the regulation of ArfGAP2, an ArfGAP whose activity is strictly coatomer-dependent. Within CM4, we define a novel hydrophobic pocket for ArfGAP2 interaction on the appendage domain of γ₁-COP. The CM4 subcomplex (but not CM3) is recruited to membranes through Arf1 and can subsequently recruit ArfGAP2. Neither CM3 nor CM4 in itself is effective in stimulating ArfGAP2 activity, but stimulation is regained when both subcomplexes are present. Our findings point to a distinct role of each of the two coatomer subcomplexes in the regulation of ArfGAP2-dependent GTP hydrolysis on Arf1, where the CM4 subcomplex functions in GAP recruitment, while, similarly to the COPII system, the cage-like CM3 subcomplex stimulates the catalytic reaction.


Aluminum concentration in deciduous teeth is dependent on tooth type and dental status.
Aluminum (Al) concentration was assessed in deciduous teeth in relation to sex, year of birth, tooth type, and the presence of caries and roots. Three hundred and twenty-three deciduous teeth from children born during the period 1952 93 in a county in southeast Sweden were sampled, and the Al content determined by graphite furnace atomic absorption spectrophotometry. The arithmetic mean of the Al concentration was 0.58 +/- 0.64 ppm dry weight (mean +/- standard deviation) and differed significantly between incisors (1.05 +/- 1.04 ppm) and canines (0.48 +/- 0.50 ppm) and between incisors and molars (0.53 +/- 0.55 ppm). A significant difference was found between teeth with and without caries. No significant differences were found between sexes. The Al concentration correlated significantly with tooth weight for incisors (r = -0.47) and canines (r = -0.45) but not for molars (r = 0.03). No significant change in Al concentration was found over time. Caries-free deciduous molars are suggested as the most useful teeth for biological monitoring of aluminum.


A 12-week, randomized, double-blind, placebo-controlled, four-arm dose-finding phase 2 study evaluating bexagliflozin as monotherapy for adults with type 2 diabetes.
To compare the safety and efficacy of bexagliflozin administered as monotherapy at three dosage strengths over a 12-week period to patients with type 2 diabetes who were either naïve to pharmacotherapy or were previously prescribed one oral hypoglycaemic agent and underwent a 6-week period of medication abstinence. Adults with type 2 diabetes (n = 292) having an HbA1c of between 7.0% and 8.5% were randomized to receive one of three dosage strengths of bexagliflozin (5, 10 or 20 mg) or placebo. The primary endpoint was the change from baseline to week 12 in the %HbA1c. Secondary endpoints included the changes from baseline in fasting plasma glucose (FPG), systolic blood pressure and diastolic blood pressure, body mass and fraction of patients achieving an HbA1c of <7%. The mixed model repeated measure estimates of the placebo-adjusted change in %HbA1c from baseline to week 12 for the 5, 10 and 20 mg groups were -0.55% (95% CI: -0.76%, -0.34%, P < 0.0001), -0.68% (95% CI: -0.89%, -0.47%, P < 0.0001) and -0.80% (95% CI: -1.01%, -0.59%, P < 0.0001), respectively. Significant and dose-dependent placebo-adjusted mean reductions from baseline to week 12 in FPG and body mass were observed. The fraction of subjects achieving an HbA1c of <7% was significantly greater in the 20 mg bexagliflozin group. The incidence of adverse events was similar for participants in all active arms (42.3%) compared with the rate measured in those receiving placebo (40.3%). Bexagliflozin confers substantial and dose-dependent benefits on subjects with type 2 diabetes and has an acceptable safety profile. Further evaluation of bexagliflozin for the control of type 2 diabetes in adults is warranted.


Isolation and characteristics of a leukemia-growth-promoting factor from calf thymus.
Leukemia-growth-promoting factor (LGPF) as we previously reported stimulates the growth of a murine leukemia subline (L17R) extensively. LGPF was isolated and 10(4) fold purified from calf thymuses by a combination of ammonium sulfate precipitation, Sephadex G-100 chromatography, hydroxylapatite chromatography, and Mono S-fast protein liquid chromatography (Mono S-FPLC). The mol. wt of LGPF was estimated to be approximately 25,000 a.m.u. from the elution pattern of Sephadex G-100 chromatography. The activity had high affinity for Mono S beads which are cation exchangers. Mono S fractions of LGPF are effective at a low concentration of 5 ng/ml. The activity was inactivated by heat (56 degrees C, 30 min), 1 mg/ml trypsin (37 degrees C, 1h), and 50 mM dithiothreitol (20 degrees C, 1h). The growth L17R leukemia cells are not only stimulated by LGPF, but also by pituitary and brain fibroblast growth factor (FGF). These data strongly suggest that LGPF is a heat sensitive cationic protein(s) acting as a member of FGF family.


2-(2-Eth-oxy-2-oxoacetamido)-benzoic acid.
The title compound, C11H11NO5, has a nearly planar geometry. In the crystal, the mol-ecules are assembled into chains parallel to the [11] direction by O-H⋯O and C-H⋯O hydrogen bonds.


Preponderance of lysosomal bodies in cultured fibroblasts from patients with recessive epidermolysis bullosa dystrophica. An electron microscopic study.
Fibroblasts of skin explants from three normal men and six patients with recessive epidermolysis bullosa dystrophica (EBD-R) were cultured in Dulbecco's medium, grown to confluence, sectioned and studied with the electron microscope. The normal control fibroblasts from the 6th to 13th passage (secretory phase) showed irregular or lobed nuclei with centrally scattered chromatin. They also had prominent RER, Golgi complexes, variously shaped mitochondria and cytoskeletal microfibrils. Their peripheral cytoplasm exhibited many vacuoles and a small number of these were autophagic lysosomes. In addition to the ultrastructural features described in the control fibroblasts, the EBD-R cells from the 6th passage contained remarkable numbers of strongly electron dense lysosomal bodies through their entire cytoplasm with very few empty vacuoles. It is speculated that the accumulation of these lysosomes may be connected with a primary metabolic cellular defect in the dermal fibroblasts of patients with EBD-R akin to that described in mucopolysaccharide storage diseases.


Ratio between the number of Th1 and Th2 lymphocytes in the peripheral blood and concentration of proinflammatory cytokines in lochia of women with postpartum endometritis.
We estimated the percentage of CD4+ lymphocytes synthesizing IFN-gamma and IL-4 in the peripheral blood and measured the concentrations of IL-1, IL-6, and TNF-alpha in lochia of patients with postpartum endometritis. T lymphocytes with intracellular IFN-gamma prevailed in women with physiological course of the postpartum period. The number of cells containing IL-4 increased in patients with postpartum endometritis. On days 5-7 after childbirth the concentrations of proinflammatory cytokines IL-1beta and TNF-alpha in lochia of these patients were higher than in healthy postpartum women (by 1.4 and 2.7 times, respectively). The concentrations of cytokines IL-1beta, TNF-alpha, and IL-6 increased most significantly in patients with postpartum endometritis and active viral infection (by 3.4, 4.2, and 1.6 times, respectively).


Endogenous prostaglandin I2 regulates the neural emergency system through release of calcitonin gene related peptide.
We previously reported that endogenous prostaglandin I(2), generated by a mild irritant, sensitised calcitonin gene related peptide (CGRP) containing sensory nerves and facilitated the release of CGRP and gastric mucosal protection against ethanol. Administration of capsaicin also inhibited ethanol induced gastric mucosal injury through immediate release of CGRP from primary sensory neurones, which is termed the neural emergency system. In the present study, we tested whether endogenous prostaglandin I(2) also modulates the cytoprotective action of capsaicin using prostaglandin I receptor knockout mice (IP(-/-)). The stomachs of IP(-/-) or their wild-type counterparts (IP(+/+)), anaesthetised with urethane (1.225 g/kg), were doubly cannulated from the oesophageal and duodenal sides, and the gastric mucosa was perfused (1 ml/min) with physiological saline. Perfusate was changed to 50% ethanol alone, or 50% ethanol containing capsaicin (16 approximately 1600 micro M). The injured area was estimated at the end of each perfusion experiment. In some animals, CGRP-(8-37), a CGRP antagonist (0.3 mg/kg), or indomethacin (1 mg/kg) was intravenously injected before perfusion of 50% ethanol containing capsaicin. Capsaicin inhibited the injured area in a dose dependent manner. Fifty per cent ethanol containing capsaicin (480 micro M) immediately increased intragastric levels of CGRP although 50% ethanol alone did not. The protective action of capsaicin (480 micro M) against ethanol was completely abolished by intravenous injection of CGRP-(8-37). Indomethacin also inhibited the protective action of capsaicin, and this was accompanied by reduced levels of intragastric CGRP. Intragastric levels of prostaglandin E(2) were not increased by capsaicin treatment but those of 6-keto-prostaglandin F(1alpha), a metabolite of prostaglandin I(2), were markedly increased. No protective action of capsaicin was observed in IP(-/-) which lacked the ability to increase intragastric CGRP levels in response to ethanol containing capsaicin. The CGRP content of the stomach from untreated IP(-/-) did not differ from those in IP(+/+). Capsaicin (160 micro M) together with intragastric perfusion of beraprost sodium (PGI(2) analogue, 2.5 micro g/ml) showed enhanced protection against ethanol induced injury. This enhanced protection was completely blocked by intravenous injection of CGRP-(8-37). The present results suggest that endogenous prostaglandin I(2) enhances the protective action of the capsaicin mediated neural emergency system against ethanol induced gastric mucosal injury through enhancement of CGRP release.


Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction who receive propranolol.
Beta blockers are frequently prescribed for survivors of acute myocardial infarction (AMI). Although ventricular ectopic activity was found to be associated with mortality in several cohorts, there are no data on the relation of ventricular ectopic activity to mortality in patients with AMI who receive beta blockers. One thousand six hundred and fifty participants in the Beta-Blocker Heart Attack Trial who were randomized to receive propranolol (60 or 80 mg 3 times daily) had 24-hour ambulatory electrocardiography at baseline. By multivariate analysis considering 16 variables, ventricular ectopic activity was independently associated with sudden death (p = 0.02 to 0.001) and total mortality (p = 0.04 to 0.0001) for an average follow-up of 25 months. By univariate analysis, ventricular ectopic activity was associated with increased total mortality (odds ratios 2.13 to 3.54) and sudden death mortality (odds ratio 2.26 to 3.93). The association of ventricular ectopic activity with mortality was observed in both high- and low-risk patient subsets with odds ratios similar to the placebo group. Thus, treatment with propranolol does not alter the relation between ventricular ectopic activity and mortality.


Outcomes of Patients With ST-Elevation Myocardial Infarction Receiving and Not Receiving Reperfusion Therapy: The Importance of Examining All Patients.
Hospitals treating patients with ST-elevation myocardial infarction (STEMI) may show good results with reperfusion treatment (fibrinolysis or primary percutaneous coronary intervention [PPCI]), but a comprehensive evaluation should factor in outcomes of patients with STEMI who do not receive reperfusion. We compared outcomes of patients receiving and not receiving reperfusion within a complete system of STEMI care by hospital type: PPCI centres, fibrinolysis centres, centres that only transfer for PPCI, and centres providing a mix of fibrinolysis and PPCI transfer. All patients presenting to 82 Quebec hospitals with characteristic symptoms, a final diagnosis of acute myocardial infarction, and core-laboratory confirmed STEMI over two 6-month periods were studied. Of the total 3731 patients with STEMI, 2918 (78.2%) received reperfusion treatment (81% PPCI, 19% fibrinolysis); 813 (21.8%) did not. For reperfusion-treated patients, 30-day mortality was 5.4% in PPCI centres, 5.4% in fibrinolysis centres, 6.9% in transfer PPCI centres, and 6.0% in mixed centres (P = 0.55). For untreated patients, 30-day mortality was 15.7% (PPCI centres), 16.1% (fibrinolysis centres), 21.8% (transfer PPCI), and 24.6% (mixed) (P = 0.08). Adjusted mortality odds ratios for all patients were 1.00 (PPCI centres), 1.50 (95% CI: 0.97-2.32; fibrinolysis centres), 1.30 (0.95-1.78; transfer PPCI centres), and 1.58 (1.09-2.29; mixed centres). PPCI was within recommended delays in 35.4%, 11.9%, and 1.2% of PPCI, transfer, and mixed centres, respectively. Mixed centres had the highest crude and adjusted all-patient 30-day STEMI mortality. Relatively good outcomes of reperfusion-treated patients, despite long treatment delays, can misrepresent overall performance if untreated patients are not examined.


Impact of p53 and PDGFR-β Expression on Metastasis and Prognosis of Patients with Pancreatic Cancer.
Identifying novel predictors of hematogenous metastasis is essential to select optimal therapeutic strategies for pancreatic cancer. The goal of this study was to clarify the clinical implications of p53 and platelet-derived growth factor receptor-β (PDGFR-β) in pancreatic cancer using immunohistochemistry (IHC). Specimens obtained by surgical resection and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the primary tumor were used for IHC. EUS-FNA was performed before any treatment. We analyzed the clinical implications of p53 and PDGFR-β IHC. We also performed a comparative analysis of the IHC findings between surgical and EUS-FNA specimens. This study involved 149 patients (120 who did not receive and 29 who received preoperative therapy). EUS-FNA specimens were obtained from 20 patients without preoperative therapy and 20 patients with preoperative therapy. Abnormal p53 and high PDGFR-β expression was significantly correlated with a high incidence of hematogenous metastasis (p < 0.001) and poor postoperative survival (p = 0.006). In patients without preoperative therapy, the results for p53 and PDGFR-β staining were concordant between surgical and EUS-FNA specimens in 95 % of the cases. In patients with preoperative therapy, 80 and 70 % of the patients showed consistent p53 and PDGFR-β expression between surgical and EUS-FNA specimens, respectively. Pancreatic cancer patients with simultaneous abnormal p53 and high PDGFR-β expression have a significantly higher risk of hematogenous metastasis and a poor prognosis after surgery. IHC evaluation using EUS-FNA specimens may be able to identify patients with highly metastatic pancreatic cancer who may benefit from aggressive therapeutic intervention.


Status of estrogen receptor expression and epigenetic methylation in Leydig cells after exposure to metalloestrogen - selenium.
The trace element selenium (Se) is essential for the maintenance of spermatogenesis and fertility. A growing volume of evidence shows that Se is necessary for testosterone synthesis, and Se can stimulate Leydig cell proliferation. However, Se can also act as a metalloestrogen, which can mimic estrogen and activate the estrogen receptors. This study aimed to investigate Se effect on estrogen signaling and the epigenetic status of Leydig cells. Mouse Leydig cells (MA-10) were cultured in a medium supplemented with different Se concentrations (4, 8 µM) for 24 h. Next, cells were assessed for morphological and molecular (qRT PCR, western blot, immunofluorescence) analyses. Immunofluorescence revealed strong immunosignal for 5-methylcytosine in both control and treated cells, with a stronger signal in the 8 μM treated group. qRT-PCR confirmed an increased expression of methyltransferase 3 beta (Dnmt3b) in 8 μM cells. Analysis of the expression of γH2AX (a marker for double-stranded DNA breaks) revealed an increase in the DNA breaks in cells exposed to 8 μM Se. Selenium exposure did not affect the expression of canonical estrogen receptors (ERα and ERβ), however, an increase in membrane estrogen receptor G-protein coupled (GPER) protein expression was observed.To sum up, in a high concentration (8 μM) Se affects GPER expression (non-genomic estrogen signaling) in Leydig cells possibly via acting on receptor protein and/or its binding. This causes DNA breaks and induces changes in Leydig cell methylation status, especially in de novo methylation which is mediated by Dnmt3b.


Biopharmaceuticals and biotechnology medicines: an issue of nomenclature.
Over the past two decades terms such as 'biopharmaceuticals' and 'biotechnology medicines' have crept into the pharmaceutical vocabulary. Such terms often have different meanings for different people and it is perhaps time that they were more formally defined.


Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a rare but highly aggressive variant of squamous cell carcinoma-report of a case and review of the literature.
Pseudoangiosarcomatous squamous cell carcinoma is an unusual but aggressive variant of acantholytic squamous cell carcinoma of the vulva that mimics angiosarcoma on histology. We present a case of a 57-year-old woman with bilateral inguinal metastatic disease at the time of diagnosis, who died 4 months later because of distant metastatic disease to the lungs. Molecular analysis did not reveal any human papillomavirus infection. Because of the positive p53 immunostaining and the association to lichen sclerosus and simple type of high-grade vulvar intraepithelial neoplasia, alteration of p53 tumor suppressor gene might be involved in the pathogenesis of vulvar pseudoangiosarcomatous squamous cell carcinoma. However, further molecular studies are required.


Numerical study of currents in workers induced by body-motion around high-ultrahigh field MRI magnets.
To numerically evaluate the electric field/current density magnitudes and spatial distributions in healthcare workers when moving through strong, nonuniform static magnetic fields generated by the magnetic resonance imaging (MRI) system and to understand the relationship between the field characteristics and levels/distributions of induced field quantities. Tissue-equivalent, whole-body male and female voxel phantoms are engaged to model the workers at various positions and variety of body motions around three real superconducting magnets with field strengths of 1.5 T, 4 T, and 7 T. The numerical calculations of induced fields are based on an efficient, quasistatic finite-difference scheme. The simulations show that it is possible to induce electric fields/current densities above levels recommended by International Commission for Non-ionizing Radiation Protection (ICNIRP) and Institute of Electrical and Electronics Engineers (IEEE) standards when the worker is moving very close to the imager. The results indicate that the worker should be at least approximately 0.5-1.0 m axially away from the cryostat end for field strengths between 1.5-7 T to limit the exposure according to the standards when moving at a nominal 1 m second(-1). To comply with international safety regulations, workers either need to be restricted in their access to certain areas around the magnet or to ensure slow movement in specified regions.


Improving physio-mechanical and biological properties of 3D-printed PLA scaffolds via in-situ argon cold plasma treatment.
As a bone tissue engineering material, polylactic acid (PLA) has received significant attention and interest due to its ease of processing and biocompatibility. However, its insufficient mechanical properties and poor wettability are two major drawbacks that limit its extensive use. For this purpose, the present study uses in-situ cold argon plasma treatment coupled with a fused deposition modeling printer to enhance the physio-mechanical and biological behavior of 3D-printed PLA scaffolds. Following plasma treatment, field emission scanning electron microscopy images indicated that the surface of the modified scaffold became rough, and the interlayer bonding was enhanced. This resulted in an improvement in the tensile properties of samples printed in the X, Y, and Z directions, with the enhancement being more significant in the Z direction. Additionally, the root mean square value of PLA scaffolds increased (up to 70-fold) after plasma treatment. X-ray photoelectron spectroscopy analysis demonstrated that the plasma technique increased the intensity of oxygen-containing bonds, thereby reducing the water contact angle from 92.5° to 42.1°. The in-vitro degradation study also demonstrated that argon plasma treatment resulted in a 77% increase in PLA scaffold degradation rate. Furthermore, the modified scaffold improved the viability, attachment, and proliferation of human adipose-derived stem cells. These findings suggest that in-situ argon plasma treatment may be a facile and effective method for improving the properties of 3D-printed parts for bone tissue engineering and other applications.


Human leukocyte antigen antibodies for monitoring transplant patients.
Human leukocyte antigen (HLA) antibody-mediated hyperacute rejection has dramatically decreased since the clinical introduction of crossmatch technology. However, the role of HLA antibody in acute and chronic rejection remains unclear. In this article, we cite publications to show the correlation between HLA antibody and allograft rejection. Potential pathological mechanisms of antibody-mediated rejection are also proposed and the rationale of commonly used HLA antibody detection techniques are introduced. The advantages and disadvantages of these technologies are further discussed in detail. We conclude that owing to the recent availability of improved antibody detection methods, a causal relationship between HLA antibodies and allograft rejection is now considered to exist.


Smoking determines the 10-year (2004-2014) prognosis in patients with Acute Coronary Syndrome: the GREECS observational study.
Smoking has long been positively associated with the development and progression of coronary heart disease. However, longitudinal cohort studies evaluating smoking habits among cardiac patients as well as the role of socio-demographic factors determining such behaviours are scarce and have been focused on primary care practice. Thus the aim of the present work was to examine the association of active smoking and behaviours and exposure to second-hand smoke, with the 10-year Acute Coronary Syndrome (ACS) prognosis, among cardiovascular patients. From October 2003 to September 2004, a sample of six Greek hospitals was selected and almost allconsecutive 2172 ACS patients were enrolled. In 2013-14, the 10-year follow-up was performed in 1918 participants (11 % loss to follow-up). Smoking habits at the time of entry to the study, as well as during the follow-up period were studied using a standard questionnaire. Patients who had >60 pack-years of smoking had 57.8 % higher ACS mortality and 24.6 % higher risk for any ACS event. Nested model, adjusted only for age and sex, revealed that for every 30 pack-years of smoking increase, the associated ACS risk increased by 13 % (95 % CI 1.03, 1.30, p = 0.001). When further adjusted analysis, including several potential confounders, was applied the tested relationship was still significant (95 %CI 1.03, 1.30, p = 0.09). Accordingly, the risk for fatal ACS events increased by 8 % for every 30 pack-years of smoking increase (95 % CI 1.03, 1.63, p = 0.06). Moreover, 52 % of the patients reported being exposed to secondhand smoke and when further adjustments were made, it was revealed that they had 33 % (95 % CI 1.12, 1.60, p = 0.01) higher risk of having recurrent ACS events. Active smoking and second-hand smoke among cardiac patients still represent a substantial clinical burden. Thus, smoking cessation policies should be incorporated into the long-term therapeutic management.


Regulation of the p75 neurotrophin receptor attenuates neuroinflammation and stimulates hippocampal neurogenesis in experimental Streptococcus pneumoniae meningitis.
Streptococcus pneumoniae meningitis is a destructive central nervous system (CNS) infection with acute and long-term neurological disorders. Previous studies suggest that p75NTR signaling influences cell survival, apoptosis, and proliferation in brain-injured conditions. However, the role of p75NTR signaling in regulating pneumococcal meningitis (PM)-induced neuroinflammation and altered neurogenesis remains largely to be elucidated. p75NTR signaling activation in the pathological process of PM was assessed. During acute PM, a small-molecule p75NTR modulator LM11A-31 or vehicle was intranasally administered for 3 days prior to S. pneumoniae exposure. At 24 h post-infection, clinical severity, histopathology, astrocytes/microglia activation, neuronal apoptosis and necrosis, inflammation-related transcription factors and proinflammatory cytokines/mediators were evaluated. Additionally, p75NTR was knocked down by the adenovirus-mediated short-hairpin RNA (shRNA) to ascertain the role of p75NTR in PM. During long-term PM, the intranasal administration of LM11A-31 or vehicle was continued for 7 days after successfully establishing the PM model. Dynamic changes in inflammation and hippocampal neurogenesis were assessed. Our results revealed that both 24 h (acute) and 7, 14, 28 day (long-term) groups of infected rats showed increased p75NTR expression in the brain. During acute PM, modulation of p75NTR through pretreatment of PM model with LM11A-31 significantly alleviated S. pneumoniae-induced clinical severity, histopathological injury and the activation of astrocytes and microglia. LM11A-31 pretreatment also significantly ameliorated neuronal apoptosis and necrosis. Moreover, we found that blocking p75NTR with LM11A-31 decreased the expression of inflammation-related transcription factors (NF-κBp65, C/EBPβ) and proinflammatory cytokines/mediators (IL-1β, TNF-α, IL-6 and iNOS). Furthermore, p75NTR knockdown induced significant changes in histopathology and inflammation-related transcription factors expression. Importantly, long-term LM11A-31 treatment accelerated the resolution of PM-induced inflammation and significantly improved hippocampal neurogenesis. Our findings suggest that the p75NTR signaling plays an essential role in the pathogenesis of PM. Targeting p75NTR has beneficial effects on PM rats by alleviating neuroinflammation and promoting hippocampal neurogenesis. Thus, the p75NTR signaling may be a potential therapeutic target to improve the outcome of PM.


Prediction of Catheter-Associated Urinary Tract Infections Among Neurosurgical Intensive Care Patients: A Decision Tree Analysis.
Catheter-associated urinary tract infections (CAUTIs) are the most common device-associated infections in hospitals and can be prevented. To identify the risk factors and develop a risk prediction model for CAUTIs among neurosurgical intensive care unit (NICU) patients. All patients admitted to the NICU of a tertiary hospital between January 2019 and January 2020 were enrolled. Two decision tree models were applied to analyze the risk factors associated with CAUTIs in NICU patients. The performance of the decision tree model was evaluated. A total of 537 patients admitted to the NICU with indwelling catheters were recruited for this study. The rate of CAUTIs was 4.44 per 1000 catheter days, and Escherichia coli was the predominant pathogen causing CAUTIs among indwelling catheter patients. The classification and regression tree model displayed good power of prediction (area under the curve : 0.920). Nine CAUTI risk factors (age ≥60 years (P = 0.004), Glasgow Coma Scale score ≤8 (P = 0.009), epilepsy at admission (P = 0.007), admission to the hospital during the summer (P < 0.001), ventilators use (P = 0.007), receiving less than 2 types of antibiotics (P < 0.001), albumin level <35 g/L (P = 0.002), female gender (P = 0.002), and having an indwelling catheter for 7-14 days (P = 0.001) were also identified. We developed a novel scoring model for predicting the risk of CAUTIs in patients with neuro-critical illness in daily clinical practice. This model identified several risk factors for CAUTI among NICU patients, novel factors including epilepsy and admission during the summer, can be used to help providers prevent and reduce the risk of CAUTI among vulnerable groups.


Practical considerations for a method of rapid cardiac function analysis based on three-dimensional speckle tracking in a three-dimensional diagnostic ultrasound system.
The purpose of this study was to validate the accuracy of our novel 3D speckle tracking method by using numerical data, and to demonstrate the rapid processing of this method by using data obtained from human subjects. In order to create a method that can rapidly assess cardiac function in regional heart wall segments, a 3D speckle tracking algorithm was created that focuses on data quality and performance. Prototype application software based on this algorithm was written to evaluate cardiac wall motion and to calculate indices such as strain. Time series 3D image data were generated for artificial numerical models that simulate the shape of the left ventricle and exhibit various types of motion. We compared observed values returned by the algorithm with expected values yielded by the models. This software was also applied to volume data of the human heart acquired by a 3D ultrasound system. Measurement of the indices was evaluated by using an error ratio that was a residual between an expected value and estimated one divided by the expected value. The average error ratio of the time series volumes was less than 5% for all indices, and no individual error ratio was more than 10% for numerical models. The process was complete within 0.5 s per frame for human heart volumes. This application software can provide good estimates of various wall motion indices. The results are similar to data from numerical models, and are provided quickly enough for routine clinical usage.


Intravenous verapamil in the treatment of paroxysmal supraventricular tachycardia in children.
Fifty-four spontaneous episodes of paroxysmal supraventricular tachycardia (PSVT) in 23 patients, varying in age from one day to fourteen years, were treated with intravenous verapamil according to a specific protocol. Stable sinus rhythm was obtained promptly with no side effects in 76% of episodes. There was no response in 9%; an unstable rhythm in 7.5%; and severe side effects (hypotension, sinus bradycardia and cardio-respiratory arrest) in 7.5%. All severe side effects were associated with larger than recommended doses of verapamil. Intravenous verapamil reverted 100% of all episodes of idiopathic PSVT in eight patients; 83% of episodes in five patients with congenital heart disease; and only 57% of episodes in nine patients with Wolff-Parkinson-White syndrome. It was ineffective in one neonate who had had intra-uterine SVT.


Detection of antibodies to bovine viral diarrhoea virus (BVDV) and characterization of genomes of BVDV from Brazil.
An ELISA for the detection of antibodies to bovine viral diarrhea virus (BVDV) was developed based on antigens derived from a genotype I BVDV strain isolated in Switzerland. Using monoclonal antibodies we showed that this antigen contained the conserved non-structural protein NS3 whereas it essentially lacked the more strain-specific E2 surface glycoprotein. This ELISA has a sensitivity of 97.5% and a specificity of 99.2% as compared to the serum neutralization test (SNT). Preliminary experiments showed that this ELISA reliably detects antibodies to BVDV strains circulating in Brazil. Serum samples obtained from 430 adult cattle on 19 farms of the State of Rio Grande do Sul (Brazil) and one farm from Corrientes (Argentina) were tested for antibodies by means of this ELISA. We found antibodies in 56% +/- 15.1% of the cattle sera tested, which indicates that, in Brazil, the prevalence of infection with BVDV is similar to that found in Europe and the USA. Our sequence analysis of two BVDV isolates showed that BVDV of both genotypes I and II circulate in Brazil.


Approaches to resection of recurrent solitary mediastinal lymph nodes after esophagectomy.
Esophageal cancer recurrence in solitary mediastinal lymph node that may possibly been left behind in the first surgery differs from other recurrence patterns because it is still local disease and offers the possibility of complete cure through resection, but it is technically difficult. We resected recurrent mediastinal lymph nodes in six cases. A left transthoracic approach was used in three patients. Other approaches were left thoracoabdominal, right open transthoracic and transcervical. R0 resections were achieved in five patients without severe surgical stress or postoperative complications. Overall survival after resection of recurrent lymph nodes was 43 (16-82) months. Approaches to resection of recurrent solitary mediastinal lymph nodes after esophagectomy should be consider to perform curative treatment safely and less invasively.


Lithium tremor and caffeine intake: two cases of drinking less and shaking more.
Lithium tremor worsened in two patients when caffeine (coffee) was eliminated from their diets. An associated reduction in renal lithium clearance resulting in increased serum lithium level is thought to be the mechanism.


Adenine base editing in an adult mouse model of tyrosinaemia.
In contrast to traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here we show in a mouse model of tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (FAH)-positive hepatocytes in the liver, and rescued weight loss in mice. We also generated FAH+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of a chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABEs. Our findings suggest that adenine base editing can be used for the correction of genetic diseases in adult animals.


The Assessment of Complications After Major Abdominal Surgery: A Comparison of Two Scales.
An accurate and reproducible method for the evaluation of postoperative morbidity is essential for a valid assessment of the outcomes of surgery. However, there is still no consensus on reporting of complications. The Clavien-Dindo classification (CDC) of complications is a validated system which reports only the most severe complication. The Comprehensive Complication Index (CCI) is a novel scale designed to capture the overall burden of complications. The aim of our study is to validate and compare the CDC and the CCI in the setting of high-risk surgical patients in whom multiple complications are common. A prospective, observational study analyzed 206 high-risk adult patients undergoing major abdominal surgery. Each postoperative complication was recorded until discharge or readmission within 30 days. The severity of complications was graded with the CDC, and the CCI was calculated subsequently. Correlations of the CDC and the CCI with hospitalization indicators and functional activity on discharge were assessed and compared. A total of 424 complications occurred in 125 (60.7%) patients. The median CCI for the cohort was 20.9 (0-44.9). CD grade II was the most frequent among patients with complications (62/125; 49.6%). The CCI and the CDC have shown a strong correlation (r = 0.969, P < 0.01). Both scales strongly correlated with the parameters of hospitalization, but the CCI showed a stronger correlation to the intensive care unit length of stay (LOS; 0.670 versus 0.628, P < 0.001), postoperative LOS (0.652 versus 0.630, P = 0.041), and prolonged intensive care unit LOS (0.604 versus 0.555, P < 0.001). The median CCI and the highest CD grade were significantly different respective to the functional activity on discharge (P < 0.001). The CDC and the CCI are the effective methods for reporting of complications after major abdominal surgery. The CCI is a more accurate scale for use in high-risk patients and correlates better with the postoperative LOS.