Elite controllers and lessons learned for HIV-1 cure.
Following the success of HIV-1 antiviral treatment that maintains undetectable levels of viral replication and lack of clinical progression, the design of an HIV-1 cure for patients became the next objective. The success of the treated individuals together with the identification of subjects that spontaneously control the clinical progression for long periods, such as long-term non-progressors (LTNPs) and particularly LTNP Elite Controllers (LTNP EC) have shed hope for the feasibility of a potential cure. Although a successful cure has not been attained yet, these patients have provided critical information on the mechanisms involved in the clinical control such as host genetic factors, as well as strong immune responses against the virus. Less attention has been paid to virological factors, particularly the association of the genetic variability and the control of viral infection. Considering all these studies, it has become clear that a combination of several host, immune and viral factors is needed to attain control of the viral replication control and the non-progressor clinical phenotype. Because this control can be reached through different combinations of factors, this group of individuals is not homogenous. As HIV-1 cure has been shown to be extremely difficult to achieve, a more feasible objective is the functional cure of the viral infection. After the analysis of multiple studies on the mechanisms of control in LTNP EC, we found subjects with various host protective factors and prolonged viral control. These subjects present a complete lack of evolution after more than 20-30 years of infection, stable levels of CD4+ cells (>400-500 cells/μl), a strong immune response, and no signs of clinical progression. We propose that individuals with these characteristics could have attained a functional cure of the HIV-1 infection.


Preparation, Purification, and Use of Fatty Acid-containing Liposomes.
Liposomes containing single-chain amphiphiles, particularly fatty acids, exhibit distinct properties compared to those containing diacylphospholipids due to the unique chemical properties of these amphiphiles. In particular, fatty acid liposomes enhance dynamic character, due to the relatively high solubility of single-chain amphiphiles. Similarly, liposomes containing free fatty acids are more sensitive to salt and divalent cations, due to the strong interactions between the carboxylic acid head groups and metal ions. Here we illustrate techniques for preparation, purification, and use of liposomes comprised in part or whole of single chain amphiphiles (e.g., oleic acids).


Impact of the EARL harmonization program on automatic delineation of metabolic active tumour volumes (MATVs).
The clinical validation of the EARL harmonization program for standardised uptake value (SUV) metrics is well documented; however, its potential for defining metabolic active tumour volume (MATV) has not yet been investigated. We aimed to compare delineation of MATV on images reconstructed using conventional ordered subset expectation maximisation (OSEM) with those reconstructed using point spread function modelling (PSF-reconstructed images), and either optimised for diagnostic potential (PSF) or filtered to meet the EANM/EARL harmonising standards (PSF7). Images from 18 stage IIIA-IIIB lung cancer patients were reconstructed using all the three methods. MATVs were then delineated using both a 40% isocontour and a gradient-based method. MATVs were compared by means of Bland-Altman analyses, and Dice coefficients and concordance indices based on the unions and intersections between each pair of reconstructions (PSF vs OSEM, PSF7 vs PSF and PSF7 vs OSEM). Using the 40% isocontour method and taking the MATVs delineated on OSEM images as a reference standard, the use of PSF7 images led to significantly higher Dice coefficients (median value = 0.96 vs 0.77; P < 0.0001) and concordance indices (median value = 0.92 vs 0.64; P < 0.0001) than those obtained using PSF images. The gradient-based methodology was less sensitive to reconstruction variability than the 40% isocontour method; Dice coefficients and concordance indices were superior to 0.8 for both PSF reconstruction methods. However, the use of PSF7 images led to narrower interquartile ranges and significantly higher Dice coefficients (median value = 0.96 vs 0.94; P = 0.01) and concordance indices (median value = 0.89 vs 0.85; P = 0.003) than those obtained with PSF images. This study demonstrates that automatic contouring of lung tumours on EARL-compliant PSF images using the widely adopted automatic isocontour methodology is an accurate means of overcoming reconstruction variability in MATV delineation. Although gradient-based methodology appears to be less sensitive to reconstruction variability, the use of EARL-compliant PSF images significantly improved the Dice coefficients and concordance indices, demonstrating the importance of harmonised-images, even when more advanced contouring algorithms are used.


Pedestrian fatalities in Alaska, 1980-1984.
During 1980-1984, 94 pedestrians (15.6% of 601 total traffic-related fatalities) were killed and 1,293 were injured in Alaska. The pedestrian fatality rate for Alaskan Natives (10.95 per 100,000 population per year) was four times the rate for non-Natives (2.84 per 100,000 population per year), and in Anchorage was 13 times higher (37.98 per 100,000 per year compared to 2.89 per 100,000 per year, respectively). Alcohol use by adult pedestrians and drivers was strongly associated with pedestrian fatal events and was especially associated with Alaskan Native pedestrian fatalities (O.R. 8, 95% CI 1.95-32.78). This previously unrecognized epidemic needs to be controlled by attacking associated risk-factors and by modifying the environment to separate pedestrians from motor vehicles.


Selective sampling of phosphopeptides for detection by MALDI mass spectrometry.
The analysis of phosphopeptides by mass spectrometry (MS) is one of the most challenging tasks in proteomics. This is due to the lower isoelectric point (pI) of phosphopeptides, which leads to inefficient sample ionization in MS, particularly when competing with other peptides. The problem is compounded by the typical low abundance of phosphopeptides in biological samples. We describe here a simple nonsorptive method to isolate phosphopeptides based on their pI. A voltage is applied to selectively migrate the phosphopeptides into a capillary, which are negatively charged at acidic pH. The selectively sampled fraction is directly deposited onto MALDI sample target in nanoliter volumes (7-35 nL) for highly sensitive MS detection. No significant sample loss is evident in this procedure; hence, the MS was able to detect the isolated phosphopeptides at trace quantity. In this case, attomole-level detection limit is achieved for synthetic phosphopeptides (nM concentration and nL volume), from a mixture containing other peptides at up to 1 million times higher in concentration. Selective sampling was also applied to the tryptic digest of beta- and alpha-caseins to reveal the multiple phosphorylated peptides at the low-femtomole level using MALDI MS. Knowledge of pI based on the rejection/injection of peptides was found to be useful in peak assignment. To confirm the sequence of the selectively sampled peptides, fraction collection was performed for offline ESI MS/MS analysis.


Molecular mimicry: a herpes virus glycoprotein antigenically related to a cell-surface glycoprotein expressed by macrophages, polymorphonuclear leucocytes, and platelets.
Bovine herpes virus type 1 (BHV-1) gIII is a major virion glycoprotein with homology to the immunoglobulin superfamily. We have investigated the possibility that gIII is related to host molecules and have identified a gIII-specific monoclonal antibody (mAb) that cross-reacts with normal bovine cells. The cross-reactive entity was expressed mainly on monocyte/macrophages (M phi), polymorphonuclear leucocytes (PMN) and platelets, and was identified as a 43,000-63,000 molecular weight (MW) cell-surface glycoprotein. For M phi, the glycoprotein appears to be a general lineage marker, rather than a maturation or activation marker, and may be a functional receptor, as evidenced by its endocytosis via coated pits and its involvement in proliferation of mononuclear cells in vitro. This novel leucocyte marker was also detected on subsets of human, ovine and canine M phi. Competitive binding assays with sera from cattle immunized with BHV-1 or gIII revealed apparent low responsiveness to the cross-reactive epitope. The results suggest that BHV-1 gIII is antigenically related to a novel host leucocyte receptor and that evasion and/or interference with leucocyte function may be a consequence of this molecular mimicry relationship.


Exploring Ecosystems and Health by Shifting to a Regional Focus: Perspectives from the Oceania EcoHealth Chapter.
This article highlights contributions that can be made to the public health field by incorporating "ecosystem approaches to health" to tackle future environmental and health challenges at a regional level. This qualitative research reviews attitudes and understandings of the relationship between public health and the environment and the priorities, aspirations and challenges of a newly established group (the Oceania EcoHealth Chapter) who are attempting to promote these principles. Ten semi-structured interviews with Oceania EcoHealth Chapter members highlighted the important role such groups can play in informing organisations working in the Oceania region to improve both public health and environmental outcomes simultaneously. Participants of this study emphasise the need to elevate Indigenous knowledge in Oceania and the role regional groups play in this regard. They also emphasis that regional advocacy and ecosystem approaches to health could bypass silos in knowledge and disciplinary divides, with groups like the Oceania EcoHealth Chapter acting as a mechanism for knowledge exchange, engagement, and action at a regional level with its ability to bridge the gap between environmental stewardship and public health.


Functional neuroimaging findings in healthy middle-aged adults at risk of Alzheimer's disease.
It is well established that the neurodegenerative process of Alzheimer's disease (AD) begins many years before symptom onset. This preclinical phase provides a crucial time-window for therapeutic intervention, though this requires biomarkers that could evaluate the efficacy of future disease-modification treatments in asymptomatic individuals. The last decade has witnessed a proliferation of studies characterizing the temporal sequence of the earliest functional and structural brain imaging changes in AD. These efforts have focused on studying individuals who are highly vulnerable to develop AD, such as those with familial genetic mutations, susceptibility genes (i.e. apolipoprotein epsilon-4 allele), and/or a positive family history of AD. In this paper, we review the rapidly growing literature of functional imaging changes in cognitively intact individuals who are middle-aged: positron emission tomography (PET) studies of amyloid deposition, glucose metabolism, as well as arterial spin labeling (ASL), task-dependent, resting-state functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) studies. The prevailing evidence points to early brain functional changes in the relative absence of cognitive impairment and structural atrophy, although there is marked variability in the directionality of the changes, which could, in turn, be related to antagonistic pleiotropy early in life. A common theme across studies relates to the spatial extent of these changes, most of which overlap with brain regions that are implicated in established AD. Notwithstanding several methodological caveats, functional imaging techniques could be preferentially sensitive to the earliest events of AD pathology prior to macroscopic grey matter loss and clinical manifestations of AD. We conclude that while these techniques have great potential to serve as biomarkers to identify at-risk individuals, more longitudinal studies with greater sample size and robust correction for multiple comparisons are still warranted to establish their utility.


Diversity and plasticity in signaling pathways that regulate smooth muscle responsiveness: Paradigms and paradoxes for the myosin phosphatase, the master regulator of smooth muscle contraction.
A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness to stimuli. Cellular MLCP activity is negatively and positively regulated in response to G-protein activation and cAMP/cGMP production, respectively, through the MYPT1 regulatory subunit and an endogenous inhibitor protein named CPI-17. In this article we review the outcomes from two decade of research on the CPI-17 signaling and discuss emerging paradoxes in the view of signaling pathways regulating smooth muscle functions through MLCP.


Fast screening for children's developmental language disorders via comprehensive speech ability evaluation-using a novel deep learning framework.
Developmental language disorders (DLDs) are the most common developmental disorders in children. For screening DLDs, speech ability (SA) is one of the most important indicators. In this paper, we propose a solution for the fast screening of children's DLDs based on a comprehensive SA evaluation and a deep framework of machine learning. Fast screening is crucial for promoting the prevalence and practicality of DLD screening which in turn is important for the treatment of DLDs and related social and behavioral abnormalities (e.g., dyslexia and autism). Our solution is focused on addressing the drawbacks existing in the previous DLD screening methods which include test failure due to text-based inducing material design and illiteracy of most young children, incomplete language evaluation indicators, and professional-reliant evaluation procedures. First, to avoid test failure, a novel comprehensive inducing procedure (CIP) with non-text (i.e., audio-visual) stimulus materials was designed that could cover a large range of modalities to adequately explore the comprehensive SA of the subjects. Second, to address incomplete language evaluation, a set of comprehensive evaluation indicators with full consideration of the characteristics of the children's language acquisition is proposed; furthermore, to break the professional-reliant limitation, we specifically designed a deep framework for fast and accurate screening. Experimental results showed that the proposed deep framework is effective and professional with a 92.6% accuracy on DLD screening. Additionally, to provide a benchmark for the novel problem, we provide a CIP dataset with about 2,200 responses from over 200 children, which may also be useful for further DLD studies and insightful for the fast screening design of other behavioral abnormalities. Fast screening of children's DLDs can be achieved at accuracy up to 92.6% by our proposed deep learning framework. For successful fast screening, an elaborated CIP with corresponding comprehensive evaluating indicators is necessary to be designed for children suspected to have DLDs.


Displacement of maxillary third molar into the infratemporal fossa. A case report.
Our study aims to present a new case of maxillary third molar dislodgement into the infratemporal fossa during the effort of extraction and the surgical approach performed to retrieve the tooth. Guidelines to prevent this complication are presented. We describe a new case of maxillary third molar displacement into the infratemporal fossa following an unsuccessful surgical procedure of tooth removal by a general dentist. The location of the displaced tooth was confirmed with computed tomography (CT) scanning with a 3D reconstruction. The tooth was removed under general anesthesia through an intraoral approach. It took less than 10 min for the whole procedure to be accomplished. CT examination is of paramount importance to precisely locate the dislodged tooth. Removal can be successfully accomplished via an intraoral approach with meticulous manipulations. An incision of adequate length and a long Langebeck retractor are valuable to ensure a wide surgical field.


Intraocular pressure measurement in patients with previous LASIK surgery using pressure phosphene tonometer.
To compare intraocular pressure (IOP) assessment in post-LASIK patients using non-contact tonometry, pressure phosphene tonometry and applanation tonometry. Sixty-two consecutive LASIK patients were analysed preoperatively and postoperatively with non-contact, pressure phosphene and applanation tonometry. Comparisons among these values were assessed with paired sample Student t-test, Pearson's correlation test and Bland-Altman plotting. There was no significant difference for preoperative IOP measurement between non-contact, pressure phosphene and applanation tonometry. The mean +/-SD difference between the preoperative non-contact tonometry and postoperative pressure phosphene tonometry IOP measurements was 0.80 +/- 2.77 mmHg (P < 0.01). Postoperative applanation tonometry significantly underestimated IOP measurement by 5.45 +/- 2.96 mmHg (P < 0.001) and postoperative non-contact tonometry significantly underestimated IOP measurement by 9.96 +/- 2.25 mmHg (P < 0.001). Pressure phosphene tonometry may provide an alternative method for the assessment of IOP in post-LASIK patients.


Quick-brain magnetic resonance imaging for nonhydrocephalus indications.
In 2002, "quick-brain" (QB) MR imaging (ultrafast spin echo T2-weighted imaging) was introduced as an alternative technique to CT scanning for assessing children with hydrocephalus. The authors have observed high patient and physician satisfaction with this technique at their institution, which has led to an increasing frequency of its use for nonhydrocephalic indications. The goal in this study was to characterize, quantitate, and assess the use of QB MR imaging for these additional indications. Between February 2003 and December 2007, 1146 consecutive QB MR imaging studies were performed, and the findings were entered prospectively into a radiology database. All available clinical records were retrospectively reviewed to assign > or = 1 of the following indications to each study: hydrocephalus, macrocephaly, Chiari malformation, intracranial cyst, screening prior to lumbar puncture, screening for congenital anomalies, trauma, and other. Changes in the distribution of indications over time and clinical experience for each indication were reviewed. The total number of QB imaging studies performed increased each year. The proportion of studies performed for nonhydrocephalic indications also increased (from 23 to 50%). The most common indication was screening for macrocephaly, and all other indications were nearly evenly distributed. Quick-brain MR imaging was used extensively for the initial evaluation and follow-up in patients with little need for additional studies. Its false-negative rate, however, remains unknown. The role of QB MR imaging for nonhydrocephalic indications is expanding, and it appears promising for a number of screening and surveillance paradigms. "Quick-brain plus" protocols for specific indications may add sensitivity and are under development.


Acute effects of hexavalent chromium on the performance and microbial community of activated sludge in aerobiotic reactors.
This study investigated the acute effects of hexavalent chromium (Cr(VI)) shock load at 2.5, 6 and 25 mg/L on the performance and bacterial community structures in aerobiotic activated sludge reactors. The results showed that eight-day Cr(VI) toxicity made the removal rates of COD and NH3-N to obviously decrease in all reactors. Furthermore, the higher the Cr(VI) concentration was, the more severe the influence on the whole system would be. The effect of Cr(VI) on NH3-N removal was more serious than that on COD and the function of nitrification was harder to recover. The specific oxygen uptake rate (SOUR) values dropped by 73%, 68% and 31% at 2.5, 6 and 25 mg Cr(VI)/L, respectively. The data of SOUR showed that though the concentration of Cr(VI) was low, the whole respiratory activity of bacteria was much affected. The relative abundance change of genus between the initial stage and the last showed that the bacterial community structure changed significantly. Comparing with the initial stage, the phyla of Proteobacteria, Acidobacteria and Planctomycetes were markedly reduced at the end stage. The genera of Ferruginibacter, Coxiella and Rhodanobacter were also markedly reduced. Although the performance of activated sludge can be restored at the end, the whole respiratory activity of bacteria was still at a low level according to the data of SOUR.


Effector-independent reduction in choice reaction time following bi-hemispheric transcranial direct current stimulation over motor cortex.
Increased reaction times (RT) during choice-RT tasks stem from a requirement for additional processing as well as reduced motor-specific preparatory activation. Transcranial direct current stimulation (tDCS) can modulate primary motor cortex excitability, increasing (anodal stimulation) or decreasing (cathodal stimulation) excitability in underlying cortical tissue. The present study investigated whether lateralized differences in choice-RT would result from the concurrent modulation of left and right motor cortices using bi-hemispheric tDCS. Participants completed a choice-RT task requiring either a left or right wrist extension. In forced-choice trials an illuminated target indicated the required response, whereas in free-choice trials participants freely selected either response upon illumination of a central fixation. Following a pre-test trial block, offline bi-hemispheric tDCS (1 mA) was applied over the left and right motor cortices for 10 minutes, which was followed by a post-tDCS block of RT trials. Twelve participants completed three experimental sessions, two with real tDCS (anode right, anode left), as well as a sham tDCS session. Post-tDCS results showed faster RTs for both right and left responses irrespective of tDCS polarity during forced-choice trials, while sham tDCS had no effect. In contrast, no stimulation-related RT or response selection differences were observed in free-choice trials. The present study shows evidence of an effector-independent speeding of response initiation in a forced-choice RT task following bi-hemispheric tDCS and yields novel information regarding the functional effect of bi-hemispheric tDCS.


Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties.
Classical concepts of atrial fibrillation (AF) have been rooted in Moe's multiple-wavelet hypothesis and simple cellular-automaton computer model. Recent experimental work has raised questions about the multiple-wavelet mechanism, suggesting a discrete "driver region" underlying AF. We reexplored the theoretical basis for AF with a 2-dimensional computer model of a 5x10-cm sheet of atrial cells with realistic ionic and coupling properties. Vagal actions were formulated based on patch-clamp studies of acetylcholine (ACh) effects. In control, a single extrastimulus resulted in a highly meandering unstable spiral wave. Simulated electrograms showed fibrillatory activity, with a dominant frequency (DF, 6.5 Hz) that correlated with the mean rate. Uniform ACh reduced core meander of the spiral wave by approximately 70% (as measured by the standard deviation of spiral-wave tip position) and accelerated the DF to 17.0 Hz. Simulated vagally induced refractoriness heterogeneity caused wavefront breakup as accelerated reentrant activity in regions of short refractoriness impinged on regions unable to respond in a 1:1 fashion because of longer refractoriness. In 7 simulations spanning the range of conditions giving sustained AF, 5 were maintained by single dominant spiral waves. On average, 3.0+/-1.3 wavelets were present (range, 1 to 7). Most wavelets were short-lived and did not contribute to AF maintenance. In contrast to predictions of the multiple-wavelet hypothesis, but in agreement with recent experimental evidence, our model indicates that AF can result from relatively stable primary spiral-wave generators and is significantly organized. Our results suggest that vagal AF may arise from ACh-induced stabilization of the primary spiral-wave generator and disorganization of the heterogeneous tissue response. The full text of this article is available at http://www.circresaha.org.


[Evaluability of the Health Gym Program in Recife, Pernambuco State, Brazil].
Implementation of the Health Gym Program is one of the key strategies in the Brazilian National Health Promotion Policy, but thus far no evaluability studies have been performed on this intervention in Recife, Pernambuco State, one of the first cities in the country to implement this intervention. This study aimed to measure the evaluability of the Health Gym Program in the city of Recife, based on the description of the intervention and the elaboration of its log frame model and theoretical models for evaluation, in addition to identifying evaluative questions. A qualitative approach was used, based on a seven-element system, by document research, interviews, and discussion with the program's managers and staff, as well as the condensation of meanings technique for analysis of the documents and interviews. The analysis showed that the program has a wide range of objectives, principles, and guidelines, and that part of the management ignores such elements. After modeling the program, the study showed the methodological and operational feasibility for the development of an evaluative survey that was discussed and negotiated with managers and workers.


Registered clinical trials on addiction: a cross-sectional study on ClinicalTrials.gov.
Clinical trials drive the development of medicine. However, little is known about the current status of clinical trials on addiction. This study aimed to provide a comprehensive analysis of registered addiction-related trials from ClinicalTrials.gov. We examined all addiction-related trials registered on ClinicalTrials.gov up to March 23, 2020. Statistical analysis was performed by using SPSS 25.0, and a two-sided p < .05 was considered statistically significant. 370 eligible trials were identified. Over half of trials were completed, while only 13.8% of trials reported results. Sample sizes varied a lot with a median number of 84 per trial. Universities were the primary sponsor for 164 (44.3%) trials, followed by hospitals (96, 26.0%). Compared to trials without results, more trials with results were sponsored by universities (62.7% vs. 41.4%, p = .003), and conducted in United States/Canada (90.2% vs. 48.3%, p < .001). Most interventional trials were randomized with a parallel assignment, and 56.3% were blinded. Thirty one (41.3%) observational trials were cohort studies and 12 (16.0%) were case-only studies. Interventional trials were more likely to be funded by the US Government, while more observational trials were supported by industries. Trials funded by the US Government were more likely to be completed than those funded by other sources (p = .009). Most registered trials on ClinicalTrials.gov about addiction were interventional trials with purpose for treatment. Most interventional trials were randomized, parallel, and masked. Our analysis highlighted the need for improvement in completing study results on the ClinicalTrials.gov.


Application of the matching law to pitch selection in professional baseball.
This study applied the generalized matching equation (GME) to pitch selection in professional baseball. The GME was fitted to the relation between pitch selection and hitter outcomes for five professional baseball pitchers during the 2014 Major League Baseball season. The GME described pitch selection well. Pitch allocation varied across different game contexts such as inning, count, and number of outs in a manner consistent with the GME. Finally, within games, bias decreased for four of the five pitchers and the sensitivity parameter increased for three of the five pitchers. The results extend the generality of the GME to multialternative natural sporting contexts, and demonstrate the influence of context on behavior in natural environments.


Proof of Concept of a Gamified DEvelopmental Assessment on an E-Platform (DEEP) Tool to Measure Cognitive Development in Rural Indian Preschool Children.
Over 250 million children in developing countries are at risk of not achieving their developmental potential, and unlikely to receive timely interventions because existing developmental assessments that help identify children who are faltering are prohibitive for use in low resource contexts. To bridge this "detection gap," we developed a tablet-based, gamified cognitive assessment tool named DEvelopmental assessment on an E-Platform (DEEP), which is feasible for delivery by non-specialists in rural Indian households and acceptable to all end-users. Here we provide proof-of-concept of using a supervised machine learning (ML) approach benchmarked to the Bayley's Scale of Infant and Toddler Development, 3rd Edition (BSID-III) cognitive scale, to predict a child's cognitive development using metrics derived from gameplay on DEEP. Two-hundred children aged 34-40 months recruited from rural Haryana, India were concurrently assessed using DEEP and BSID-III. Seventy percent of the sample was used for training the ML algorithms using a 10-fold cross validation approach and ensemble modeling, while 30% was assigned to the "test" dataset to evaluate the algorithm's accuracy on novel data. Of the 522 features that computationally described children's performance on DEEP, 31 features which together represented all nine games of DEEP were selected in the final model. The predicted DEEP scores were in good agreement (ICC [2,1] > 0.6) and positively correlated (Pearson's r = 0.67) with BSID-cognitive scores, and model performance metrics were highly comparable between the training and test datasets. Importantly, the mean absolute prediction error was less than three points (<10% error) on a possible range of 31 points on the BSID-cognitive scale in both the training and test datasets. Leveraging the power of ML which allows iterative improvements as more diverse data become available for training, DEEP, pending further validation, holds promise to serve as an acceptable and feasible cognitive assessment tool to bridge the detection gap and support optimum child development.


Discrimination of Brazilian lager beer by 1H NMR spectroscopy combined with chemometrics.
1H NMR spectroscopy combined with chemometrics was employed to discriminate lager beer samples from two different classes, according to their style and information provided on the label. Partial replacement of barley malt by adjuncts is a common practice adopted by large breweries, which can lead to a decrease in diastatic power, requiring the use of exogenous enzymes. For this reason, small variations in the spectral profile can occur in the carbohydrates region. Many studies have focused on differentiating beers according to type and brewing process. However, there have no studies concerning the discrimination of beers of the same type that differ only in style, using 1H NMR spectroscopy. In this study PCA (first three components explained 81.5% of the dataset variability), PLS-DA and SIMCA models proved to be powerful tool with predict power higher than 90% for distinguishing lager beers based on the raw materials employed in the brewing process.


Pancreatic Divisum: An Unusual Cause of Chronic Pancreatitis in a Young Patient.
Pancreatic divisum is a condition that occurs in 4-14% of the population. Pancreatic divisum occurs in development when the ventral bud and dorsal bud of the pancreas fail to fuse. Patients with this condition are usually asymptomatic, however, 25-38% of these patients experience recurrent pancreatitis that may further progress to chronic pancreatitis. This case is of a 20-year-old female presenting with abdominal pain in the left and right upper quadrants of the abdomen with a significant history of recurrent pancreatitis since the age of seven. The patient was examined with computed tomography (CT), which identified pancreatitis. Further magnetic resonance cholangiopancreatography (MRCP) assisted in the diagnosis of a type III pancreatic divisum, given the remnant of short communication between the dorsal and ventral duct.


Practical recommendations for home-nebulized corticosteroid use in children aged ≤ 5 years with asthma: A review and advisory group consensus.
Despite nebulized budesonide being identified by the Global Initiative for Asthma report as a viable alternative to inhaled corticosteroids (ICS) delivered by pressurized metered-dose inhalers (pMDIs) with spacers, practical guidance on nebulized corticosteroid use in the pediatric population remains scarce. To review the current literature and provide practical recommendations for nebulized budesonide use in children aged ≤ 5 years with a diagnosis of asthma. A group of 15 expert pediatricians in the respiratory and allergy fields in Thailand developed Delphi consensus recommendations on nebulized budesonide use based on their clinical expertise and a review of the published literature. Studies that evaluated the efficacy (effectiveness) and/or safety of nebulized budesonide in children aged ≤ 5 years with asthma were assessed. AR patients. Overall, 24 clinical studies published between 1993 and 2020 met the inclusion criteria for review. Overall, results demonstrated that nebulized budesonide significantly improved symptom control and reduced exacerbations, asthma-related hospitalizations, and the requirement for oral corticosteroids compared with placebo or active controls. Nebulized budesonide was well tolerated, with no severe or drug-related adverse events reported. Following a review of the published evidence and group consensus, a treatment algorithm as per the Thai Pediatric Asthma 2020 Guidelines was proposed, based on the availability of medications in Thailand, to include nebulized budesonide as the initial treatment option alongside ICS delivered by pMDIs with spacers in children aged ≤ 5 years. ThNebulized budesonide is an effective and well-tolerated treatment option in children aged ≤ 5 years with asthma.


Probiotic therapy reduces periodontal tissue destruction and improves the intestinal morphology in rats with ligature-induced periodontitis.
With increase in the incidence of resistance to antibiotics, probiotics are emerging as a promising adjunctive periodontal therapy. The authors of this study evaluate the influence of probiotic (PROB) supplementation on ligature-induced periodontitis (LIP) and intestinal morphology in rats. Thirty-two rats were randomly divided into four groups: control (C), LIP, PROB, and LIP/PROB. In groups PROB and LIP/PROB, the PROB was administered orally by addition to the drinking water of the animals for 44 days. In groups LIP and LIP/PROB, the mandibular right first molar of the animals received a cotton ligature that was left in the same position for 14 days. All animals were euthanized 44 days after the start of the PROB supplementation. The jaws were resected and histomorphometric analyses were performed. The measurements included evaluation of attachment loss (AL) and alveolar bone level (ABL) on the distal root of the mandibular first molar. Samples of the duodenum, jejunum, and ileum were also dissected from each animal to evaluate the villous height (VH) and crypt depth (CD). The data obtained were subjected to statistical analyses (analysis of variance, Tukey; P <0.05). Mean values of AL and ABL were significantly higher in group LIP compared with group LIP/PROB (AL: 3.05 ± 0.57 mm and 1.78 ± 0.63 mm, respectively; ABL: 4.21 ± 0.42 mm and 3.38 ± 0.17 mm, respectively). In group LIP/PROB, the mean values of VH and CD of the jejunum were significantly higher than the ones from group LIP (VH: 672.1 ± 83.3 µm and 528.0 ± 51.7 µm, respectively; CD: 463.8 ± 100.9 µm and 269.0 ± 48.4 µm, respectively). It can be concluded that PROB supplementation 1) reduces AL and alveolar bone loss in rats with LIP and 2) can protect the small intestine from reactive changes induced by LIP.


Monoclonal antibodies against antigens of the human mammary carcinoma cell line MCF-7.
Mouse monoclonal antibodies against the human mammary carcinoma cell line, MCF-7, were produced and tested against a panel of cell lines. They recognize a variety of intra- and extracellular antigens. Four of them did not react with the human rhabdomyosarcoma cell line A-204 used as a discriminating second target during initial screening. One of these, 45-B/B3, is specific for epithelia, and probably recognizes a cytokeratin. This antibody clearly differentiates carcinomas from sarcomas and lymphomas, and epithelial cells in culture from fibroblasts. It is not species-restricted.


Clinical experience with sotalol in the treatment of cardiac arrhythmias.
The treatment of cardiac arrhythmias has changed over the past several years, as concerns have grown about proarrhythmias and increased mortality associated with certain antiarrhythmic agents. Sotalol, a unique racemic compound with both Class II (beta-blocking) and Class III (repolarization-prolonging) properties, effectively controls life-threatening arrhythmias and has a favorable safety profile, especially when compared with traditional antiarrhythmic drugs. A review of clinical trials demonstrates that sotalol is an effective treatment for premature ventricular complexes, ventricular tachycardia, and ventricular fibrillation. Moreover, it significantly reduces cardiac and all-cause mortality in these patient populations. Although sotalol currently is approved in the United States only for the treatment of life-threatening ventricular arrhythmias, it also is active against several supraventricular arrhythmias. Sotalol is safe and generally well tolerated; most of the adverse effects experienced with its use are related to its beta-blocking activity. However, sotalol has been associated with life-threatening proarrhythmias, including torsades de pointes, but the incidence of this adverse effect is low. Unlike pure Class II agents, sotalol usually is well tolerated in patients with mild-to-moderate left ventricular dysfunction and rarely causes new or worsening congestive heart failure. Sotalol represents an advance in the treatment and prevention of symptomatic ventricular arrhythmias and appears to be a reasonable first-line choice when the arrhythmia is life threatening.


Effects of traditional medical herbs "minor bupleurum decoction" on the non-specific immune responses of white shrimp (Litopenaeus vannamei).
This study is investigating the effect of minor bupleurum decoction (Xiao-Chai-Hu decoction) on the non-specific immune response of white shrimp (Litopenaeus vannamei). To determine prophenoloxidase activity (proPO), reactive oxygen species production (ROS), superoxide anion production (O2-), nitric oxide production (NO), phagocytic rate (PR), phagocytic index (PI), superoxide dismutase activity (SOD), total haemocyte count (THC) and differential haemocyte count (DHC). In this experiment, treating with different dosages (0, 0.25, 0.5 and, 1%) of minor bupleurum decoction to detect immune parameters on day 0, 1, 2, 4, 7, 14, 21 and 28. Result is shown that 0.25% treatment significantly enhanced the superoxide dismutase (SOD) activity and, 0.25 and 1% treatment significantly increased the ROS production, nitric oxide (NO) production and phagocytic rate (PR) moreover, 0.5 and 1% treatment induced the proPO activity and superoxide anion (O2-) production. Evidence exactly indicated that minor bupleurum decoction is able to enhance the non-specific immunity responses of white shrimp via in vivo examination.


Time trends in diagnostic strategy, treatment, and prognosis of gastric cancer in the elderly: a population based study.
The impact of changes in diagnostic strategies for gastric cancer and attitudes towards surgery in elderly patients is not known. A population-based series of 842 gastric cancers diagnosed between 1976 and 1993 in patients aged 70 and older in Côte-dOr, France, was used to establish trends in diagnostic strategy, treatment, and prognosis. The use of endoscopy alone increased from 3% (1976-78) to 81% (1991-93). This trend was initially associated with a decrease in the use of x-ray alone, then with a decrease in the use of both x-ray and endoscopy. The proportion of resection for cure increased from 26% during 1976-78 to 43% during 1991-93 (P < 0.001). The proportion of cancers not extending beyond the gastric wall increased from 12% to 24% (P < 0.05). Operative mortality decreased from 38.7% (1976-78) to 13.3% (1991-93) and the corresponding 3-year crude survival rate rose from 7% to 18%. Improvements in the care of gastric cancer in elderly patients have been achieved, but further progress is warranted.


Identifiability of Components of Complex Interventions Using Factorial Designs.
The aim of this contribution is to demonstrate how the component structure of a complex intervention (CI) can be efficiently exploited for study design and statistical analysis by using concepts of factorial designs. Many studies on CIs in complementary and alternative medicine exhibit the structure of factorial designs, where all possible combinations of the levels of two or more treatments occur together. In this contribution, the treatment arms of CI studies are explicitly viewed as factorial combinations of their components. Experimental design offers the general concept of identifiability of effects, that is, unique estimability of the components' effects from the observed data. For factorial designs, a simple cross table representation of the treatment arms can show the components or sums or interactions of components that are identifiable within a given study design. The question of identifiability arises particularly if some combinations of components are not observed (e.g., individualized homeopathic prescription without consultation). Study designs from published homeopathy studies are used for demonstration. CI studies should explicitly use an intervention's factorial component structure if it is inherent in the treatment arms being compared. In this way, investigators can avoid study designs from which the effects of interest cannot be uniquely estimated and improve the interpretation of estimated effects.


Hepatic pseudolesion around the falciform ligament: prevalence, aberrant venous supply, and fatty infiltration evaluated by multidetector computed tomography and magnetic resonance imaging.
The aim of this study was to determine the prevalence and aberrant venous supply (inferior veins of Sappey) of hypoattenuating hepatic pseudolesions seen around the falciform ligament on portal-dominant phase multidetector computed tomography (MDCT) and the frequency of fatty infiltration of these pseudolesions on chemical-shift magnetic resonance imaging. Portal-dominant phase abdominal MDCT examinations of 728 patients were evaluated for the presence of a pseudolesion around the falciform ligament, and those with a presumed pseudolesion underwent chemical-shift magnetic resonance imaging to detect the fatty infiltration. Reconstructed MDCT images were investigated for the presence of an inferior vein of Sappey, and 30 patients without a pseudolesion were evaluated as a control group. A total of 160 pseudolesions were detected around the falciform ligament in 146 (20%) patients. The longest diameter of the pseudolesions was in the craniocaudal direction in most patients (61%). An inferior vein of Sappey supplying these pseudolesions was depicted in 40 (27%) patients, and it was highly significant (P = 0.001) compared with the controls for the presence of a pseudolesion around the falciform ligament. Fatty infiltration was found in 47 (29%) patients. Hepatic pseudolesions around the falciform ligament are frequently encountered on portal-dominant phase MDCT images. Detection of craniocaudal extension, inferior veins of Sappey, and fatty infiltration of these pseudolesions, which were firstly described in this article, with the largest subject group based on cross-sectional imaging, might be valuable in excluding true tumors.


Effects of 14 Versus 21 Days of Nimodipine Therapy on Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage Patients.
Oral nimodipine is standard therapy for patients suffering an aneurysmal subarachnoid hemorrhage (aSAH). During a national drug shortage, nimodipine therapy was shortened from a 21-day course to a 14-day course at our institution. The objective of this study was to compare neurological outcomes among patients who had previously received the standard duration of therapy compared with those who received a shortened duration as a result of the national drug shortage. This retrospective cohort study evaluated adult patients receiving nimodipine for aSAH from January 2012 to August 2013. Neurological outcome, graded by Modified Rankin Scale (mRS) at hospital discharge, was compared between patients receiving a shortened course and those receiving the standard duration of nimodipine. A total of 199 aSAH patients were included in the analysis. There were 164 patients in the standard-duration and 35 patients in the shortened-duration group. Baseline patient severity of illness, assessed by SAPS II (Simplified Acute Physiology Score), and severity of aSAH, assessed by Fisher grade, and Hunt and Hess grade scores, did not differ between the treatment groups. A shortened duration of nimodipine was not associated with a higher risk of a poor neurological outcome defined by mRS (odds ratio = 1.85; 95% CI = 0.54-6.32; P = 0.32). Mortality rates were similar between the groups. A 14-day course of nimodipine therapy was not associated with worse neurological outcomes in aSAH patients at one institution. More studies are needed prior to recommending a shortened duration of nimodipine therapy in all aSAH patients.


Swollen cortical neurons in Creutzfeldt-Jakob disease contain a phosphorylated neurofilament epitope.
The distribution of swollen neurons and the presence of a phosphorylated neurofilament protein (NFP) epitope in these cells were studied in six cases of Creutzfeldt-Jakob disease (CJD). Swollen neurons are widely distributed in the cerebral cortex and are most abundant in the cingulate and parahippocampal gyri. They are more numerous in the panencephalopathic type of CJD than in the subacute spongiform encephalopathic type. A phosphorylated epitope of NFP was detected in the perikarya of swollen neurons by an immunocytochemical method using a series of monoclonal antibodies that distinguish phosphorylated and nonphosphorylated epitopes of NFP. This abnormal distribution of phosphorylated NFP epitopes indicates that the process of NFP phosphorylation is altered in neurons affected by CJD. This investigation, in accordance with previous studies, suggests that the abnormal post-translational modification of the neurofilament may play an important role in the pathogenesis of several neurodegenerative disorders.


Study of compositions of musks in different types secreted by forest musk deer (Moschus berezovskii).
Musk is a secretion of the forest musk deer (Moschus berezovskii). Normal musk is a brown solid secretion with a light fragrance. In this study, abnormal types of musk, namely, white and black musks, were discovered during the musk collection process. Researchers have long been concerned with the components of musk. Herein, GC-MS, headspace solid-phase microextraction (HS-SPME), and nonmetric multidimensional scaling (NMDS) were used to analyze the nonpolar organic components, volatile organic components, and sample similarities among different musks, respectively. Abundant steroid hormones and proteins were also found in the musk. The steroid hormone concentrations were detected using a radioimmunoassay (RIA). Proteins in the samples were hydrolyzed and the amino acids concentrations were detected. The steroid hormone and amino acid concentrations in white musk were significantly lower than in normal and black musks (p<0.05). The components were subjected to NMDS analysis to understand the differences in components among different types of musk, with the results suggesting that white musk was different from normal and black musks.


A Custom-Made Nostril Retainer for Adult Population.
Nostril retainers are used in cleft lip nose surgery in the post-operative period to maintain alar diameter and resistance against contraction. Various custom made splints were described in the literature to mimic this function when nostril retainers cannot be used for economic or logistic reasons. The authors designed a nostril retainer made by silicone urinary catheter for adult age patients which can be prepared easily. The splint can be used in both unilateral cleft lip nose surgery and operations in the alar wing of the nose.


Psychiatric disorders in and service use by young homeless people.
To examine psychiatric morbidity, including substance use disorders, and service use in young people with experience of homelessness. A cross-sectional study of 34 new residents in a supported accommodation program in Melbourne. Current and lifetime psychiatric diagnoses were made using the Structured Clinical Interview for the Diagnostic and statistical manual of mental disorders, third edition, revised (DSM-III-R). Use of psychiatric and related services was also assessed. Of the 21 women and 13 men (mean age, 18.1 years; standard deviation, 2.2 years), 50% had a current major DSM-III-R diagnosis, and 82% had a lifetime DSM-III-R diagnosis. The most common diagnoses were alcohol dependence, depressive disorders and cannabis dependence. Co-morbidity was common. Few of the young people had sought or received any treatment for depressive or substance use disorders. Young people with experience of homelessness have a high prevalence of depressive disorders and substance use disorders, particularly alcohol and cannabis dependence. Despite this they have a low rate of service use. These findings suggest a need for closer interaction between mental health professionals and other agencies in the planning and provision of services to young homeless people.


Acetic, propionic, and oleic acid as the possible factors influencing the predominant residence of some species of Propionibacterium and coagulase-negative Staphylococcus on normal human skin.
The minimum inhibitory concentration (MIC) of acetic and propionic acid for resident bacteria on normal human skin, such as Propionibacterium acnes and Staphylococcus epidermidis, was 25 mg/mL or more at any pH tested (pH 5.5-6.8). While the MIC of these acids for most of the transient bacteria was markedly decreased by lowering the pH of the media and at pH 5.5, the mean pH value of the normal human skin, the MIC was 6.25 mg/mL or less. The MIC of oleic acid for some strains of Gram-positive transient bacteria of Streptococcus, Micrococcus, or Bacillus was 100 micrograms/mL or less at all pH's tested. Staphylococcus aureus was resistant to this acid at pH 6.8, but became as sensitive as Streptococcus when the pH was lowered. The growth of P. acnes, the most predominant resident bacterium, was enhanced markedly and reached a maximum level at 6.25 mg/mL of propionic acid, 12.5 mg/mL of acetic acid, and 50-100 micrograms/mL of oleic acid. On the basis of these results, we presumed that acetic, propionic, and oleic acids are factors influencing the predominant residence of some species of Propionibacterium and coagulase-negative Staphylococcus on normal human skin.


Molecular surveillance of measles and rubella in the WHO European Region: new challenges in the elimination phase.
The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus spread across the EUR by mobile groups has recently led to large outbreaks in the insufficiently vaccinated resident population. As an instrument for monitoring the elimination process and verifying the interruption of endemic virus transmission, molecular surveillance has to provide valid and representative data. Irrespective of the country's specific situation, it is required to ensure the functionality of the laboratory surveillance that is supported by the WHO Global Measles and Rubella Laboratory Network. To investigate whether the molecular surveillance in the EUR is adequate for the challenges in the elimination phase, we addressed the quality assurance of molecular data, the continuity and intensity of molecular monitoring, and the analysis of transmission chains. Published articles, the molecular External Quality Assessment Programme of the WHO, the Centralized Information System for Infectious Diseases of the WHO EUR and the WHO Measles and Rubella Nucleotide Surveillance databases served as information sources. Molecular proficiency testing conducted by the WHO in 2016 has shown that the expertise for measles and rubella virus genotyping exists in all parts of the EUR. The analysis of surveillance data reported nationally to the WHO in 2013-2016 has revealed some countries with outbreaks but not sufficiently representative molecular data. Long-lasting supranational MV transmission chains were identified. A more systematic molecular monitoring and recording of the transmission pattern for the whole EUR could help to create a meaningful picture of the elimination process.


Rehabilitation of Executive Function Impairments after Stroke.
Recent advances in neuropsychological research reveal the importance of cognitive function in stroke rehabilitation. Executive function is the highest function of the cognitive process, however, studies focused on rehabilitation outcomes are rare. Three ACoA aneurysm rupture survivors are trained with self-instructional training, a problem-solving procedure, and physical-set changing exercises for 6 months. Two subjects improved their scores on a neuropsychological test (Tinker-Toy Test) after problem-solving training. Patients revealed improvement in all activities in their everyday lives, including ADLs, instrumental ADLs, leisure activities, etc. These results suggest that a remedy for executive function impairments must be a fruitful area for future research in stroke rehabilitation.


Acromioclavicular joint fixation using an acroplate combined with a coracoclavicular screw.
Appropriate treatment of acromioclavicular joint dislocation is controversial. Acroplate fixation is one of the most common treatment methods of acromioclavicular joint (ACJ) dislocation. Based on the risk of re-dislocation after Acroplate fixation, we assumed that combined fixation with an Acroplate and a coracoclavicular screw helps improve the outcome. The main purpose of the current study was to compare the outcome of ACJ dislocation treated with an Acroplate alone and in combination with coracoclavicular screw. This study was carried out on 40 patients with ACJ dislocation types III to VI who were divided randomly into two equal groups: Acroplate group (P) and Acroplate in combination with coracoclavicular screw group (P + S). The screws were extracted 3-6 months postoperatively. The patients were followed for 1 year and Imatani's score was calculated. Finally, the data were compared between the groups. The mean Imatani's score was significantly higher in P + S group (83.4 ± 14.1) than P group (81.2 ± 10.3) (P < 0.001). The mean duration of surgery was the same in the two groups (59.8 ± 9.4 minutes in group P V.s 64.3 ± 10.9 minutes in group P + S; P = 0.169). There were no cases of re-dislocation, degenerative changes and ossification and all patients returned to their previous jobs or sporting activities. Using a coracoclavicular screw combined with an Acroplate can improve the patients' function after ACJ disruption without any significant increase in surgical duration. Authors recommend this technique in the fixation of ACJ dislocation.


Induction of apoptosis by telomere 3' overhang-specific DNA.
Telomeres are tandem repeats of a specific TTAGGG nucleotide sequence at the ends of chromosomes. Telomere shortening is proposed to act as a biological clock and cancer prevention mechanism by inducing a nonproliferative, senescent phenotype after a limited number of cellular divisions. Recent evidence also suggests that telomere disruption can trigger apoptosis in certain cell types, mimicking a major cellular response to DNA damage. Here, we show that addition of DNA oligonucleotides homologous to the telomere 3' overhang sequence causes lymphocytic (Jurkat) cells to undergo apoptosis, as described for lymphocytes following telomere loop disruption. We further implicate the p53 tumor suppressor and transcription factor, as well as the p53 homolog p73 and the E2F1 transcription factor, in mediating the apoptotic response. We propose that exposure of the telomere 3' overhang due to opening of the normal telomere loop structure is a physiologic signal for these DNA damage-like responses in vivo and that oligonucleotides partially or completely homologous to the telomere overhang mimic this signal in the absence of DNA damage or telomere disruption.


Origin of the ligand effect in the cobalt catalyzed regioselective hydroboration of 1,3-diene.
Hydroboration of 1,3-dienes can provide useful intermediates with multiple functionalities. However, achieving high regioselectivity is still a challenge. Recent experimental research studies indicate that this challenge could be overcome by the ligand effect. We made DFT calculations to elucidate the origin of ligand controlled regioselectivity in cobalt catalyzed hydroboration of 2-substituted 1,3-diene. The following conclusions have been reached: when using PHOX ((2-oxazolinyl)-phenyldiphenylphosphine) as the ligand, the favorable 1,4-selective oxidative hydrogen migration pathway was suggested to start with the rate-determining step of 1,4-selective oxidative hydrogen migration followed by reductive boryl migration. The unique 1,4-selectivity is proposed to be a result of the less steric hindrance between the substrate and the ligand PHOX. When dppp (1,3-bis-(diphenylphosphino)propane) is used as the ligand, the favorable pathway is proposed to be a 1,2-selective oxidative boryl migration pathway which involves 1,2-selective oxidative boryl migration and reductive hydrogen migration. Interestingly, another smaller-bite angle bisphosphine ligand dppe (1,2-bis(diphenylphosphino)ethane) favors the 1,4-selective oxidative boryl migration pathway. DFT calculations revealed that the preferred oxidative boryl migration pathway with both dppp and dppe is attributed to their electron-rich properties which accelerate the oxidative boryl migration step. The larger bite angle of dppp than that of dppe leads to bulkier steric hindrance and promotes 1,2-selective reductive hydrogen migration. On the other hand, for dppe with a smaller bite angle, the steric effect in the reductive hydrogen migration step is not dominant and 1,4-selective reductive hydrogen migration is favored. It is expected that the analysis of the ligand effect on the regioselectivity would enable further catalyst design.


Afatinib, an irreversible ErbB family blocker, with protracted temozolomide in recurrent glioblastoma: a case report.
There are few effective treatments for recurrent glioblastoma multiforme (GBM). We present a patient with recurrent GBM who achieved a prolonged response to treatment with afatinib, an irreversible ErbB family blocker, plus temozolomide. A 58-year-old female patient was diagnosed with multifocal primary GBM. After surgical resection, first-line therapy comprised radiotherapy and temozolomide. Following disease progression after 3 temozolomide cycles, the patient entered a phase I/II clinical trial of afatinib (20-40 mg daily for 28 days) plus temozolomide (50 mg/m2 every 21/28 days). Next-generation sequencing analysis of the brain tumor specimen was performed. At the last assessment, 63 treatment cycles had been completed and the patient had survived for ~5 years since recurrence. Significant disease regression was observed after 5 cycles and was maintained during long-term follow-up. Adverse events were consistent with the known tolerability profile of afatinib and were managed by treatment interruption/dose reduction. The patient had several epidermal growth factor receptor (EGFR) aberrations, including gene amplification and EGFRvIII positivity. Three somatic mutations were identified, including an unprecedented extracellular-domain substitution (D247Y). The patient has survived ~6-fold longer than normally expected in patients with recurrent GBM. The complex EGFR genotype may underlie sustained response to afatinib plus temozolomide.


Molecular Epidemiology of Pseudomonas syringae pv. syringae Causing Bacterial Leaf Spot of Watermelon and Squash in Florida.
From 2013 to 2014, bacterial leaf spot epidemics incited by Pseudomonas syringae pv. syringae affected an estimated 3,000 ha of watermelon and squash in Florida, and caused foliar blighting and transplant losses in severely affected fields. To investigate the diversity of the causal agent, we isolated 28 P. syringae strains from diseased plants grown in 10 Florida and Georgia counties over the course of 2 years. Strains were confirmed as P. syringae through sequence analysis of the 16S ribosomal RNA, phenotypic, and biochemical profiling; however, 20 displayed an atypical phenotype by exhibiting nonfluorescent activity on King's medium B agar and being negative for ice-nucleating activity. Multilocus sequence analysis and BOX polymerase chain reaction revealed the presence of two haplotypes among the collected strains that grouped into two distinct clades within P. syringae phylogroup 2. Pathogenicity testing showed that watermelon, cantaloupe, and squash seedlings were susceptible to a majority of these strains. Although both haplotypes were equally virulent on cantaloupe, they differed in virulence on watermelon and squash. The distribution of one haplotype in 9 of 10 Florida and Georgia counties sampled indicated that these epidemics were associated with the recent introduction of a novel clonal P. syringae lineage throughout major watermelon production areas in Florida.


Diagnostic performance of angiography-based quantitative flow ratio for the identification of myocardial ischemia as assessed by 13N-ammonia myocardial perfusion imaging positron emission tomography.
Quantitative flow ratio (QFR) is a novel, adenosine-free method for functional lesion interrogation based on 3-dimensional quantitative coronary angiography and computational algorithms. We sought to investigate the diagnostic performance of QFR versus myocardial perfusion imaging positron emission tomography (MPI-PET), which yields the highest accuracy for detection of myocardial ischemia. Diagnostic performance of QFR versus MPI-PET was assessed in consecutive patients undergoing both clinically indicated coronary angiography and 13N-ammonia MPI-PET within a six-month period. Out of 176 patients (439 coronary arteries), 19.3% were women. Percent area stenosis was 45 [32-58] %. Myocardial ischemia on 13N-ammonia MPI-PET was detected in 106 (24.1%) vessel territories and hemodynamic significance defined as contrast-flow vessel QFR ≤ 0.80 was observed in 83 (18.9%) vessels. Diagnostic accuracy, sensitivity, and specificity of contrast-flow vessel QFR for the prediction of myocardial ischemia on 13N-ammonia MPI-PET were 92.5 (95% CI 89.6-94.7) %, 73.6 (95% CI 64.1-81.7) %, and 98.5 (95% CI 96.5-99.5) %, respectively. The AUCs for contrast-flow vessel QFR, percent diameter stenosis, and percent area stenosis were 0.85 (95% CI 0.81-0.88, p < 0.001), 0.76 (95% CI 0.71-0.79, p < 0.001) and 0.75 (95% CI 0.70-0.79, p < 0.001), respectively. QFR, a novel diagnostic tool for functional coronary lesion assessment, provides good diagnostic agreement with MPI-PET and superior diagnostic accuracy for the detection of myocardial ischemia as compared to anatomic indices. Future studies will have to determine the non-inferiority of QFR to fractional flow reserve with respect to clinical outcomes.


Proteomic insights into cardiac cell death and survival.
Cardiovascular disease is the leading cause of death and disability in the developed world. To design novel therapeutic strategies to treat and prevent this disease, better understanding of cardiac cell function is necessary. In addition to (and, indeed, in combination with) genetics, physiology and molecular biology, proteomics plays a critical role in our understanding of cardiovascular systems at multiple scales. The purpose of this review is to examine recent developments in the field of myocardial injury and protection, examining how proteomics has informed investigations into organelles, signaling complexes, and cardiac phenotype.


THE GENETICS OF PHENOTYPIC PLASTICITY. VIII. THE COST OF PLASTICITY IN DAPHNIA PULEX.
In a heterogeneous world, the optimal strategy for an individual is to continually change its phenotype to match the optimal type. However, in the real world, organisms do not behave in this fashion. One potential reason why is that phenotypic plasticity is costly. We measured production and maintenance costs of plasticity in the freshwater crustacean Daphnia pulex (Cladocera: Crustacea) in response to the presence of chemical signals from a predator, the insect Chaoborus americanus. We looked at three changes in juvenile body size and shape: body length, body depth, and tailspine length. Fitness costs were measured as changes in adult growth and fecundity, and summarized as the intrinsic rate of increase (r) for individuals reared in the presence or absence of Chaoborus extract. The cost of plasticity was measured as a multiple regression of mean clone fitness against trait and trait plasticity. We found scant evidence for either production or maintenance costs of plasticity. We also failed to find direct costs of these juvenile structures, which is surprising, as others have found such costs. We attribute the lack of measurable direct or plasticity costs to a decrease in metabolic rates in the presence of the Chaoborus extract. This decrease in metabolic rate may have compensated for any cost increases. We call for more extensive measures of the costs of plasticity, especially under natural conditions, and the incorporation of costs into evolutionary models.


Sample-based approach can outperform the classical dynamical analysis - experimental confirmation of the basin stability method.
In this paper we show the first broad experimental confirmation of the basin stability approach. The basin stability is one of the sample-based approach methods for analysis of the complex, multidimensional dynamical systems. We show that investigated method is a reliable tool for the analysis of dynamical systems and we prove that it has a significant advantages which make it appropriate for many applications in which classical analysis methods are difficult to apply. We study theoretically and experimentally the dynamics of a forced double pendulum. We examine the ranges of stability for nine different solutions of the system in a two parameter space, namely the amplitude and the frequency of excitation. We apply the path-following and the extended basin stability methods (Brzeski et al., Meccanica 51(11), 2016) and we verify obtained theoretical results in experimental investigations. Comparison of the presented results show that the sample-based approach offers comparable precision to the classical method of analysis. However, it is much simpler to apply and can be used despite the type of dynamical system and its dimensions. Moreover, the sample-based approach has some unique advantages and can be applied without the precise knowledge of parameter values.


Long non-coding RNA LSINCT5 predicts negative prognosis and exhibits oncogenic activity in gastric cancer.
Long non-coding RNAs (lncRNAs) are recently discovered RNA transcripts that are aberrantly expressed in many tumor types. Numerous studies have suggested that lncRNAs can be utilized for cancer diagnosis and prognosis. LSINCT5 (long stress-induced non-coding transcript 5) is dramatically upregulated in breast and ovarian cancer and affects cellular proliferation. However, the expression pattern of LSINCT5 in gastrointestinal cancer and the association between aberrant expression of LSINCT5 in gastrointestinal cancer and malignancy, metastasis, or prognosis remain unknown. LSINCT5 expression was detected in gastrointestinal cancer and paired adjacent normal tissue samples or cell lines using reverse transcription quantitative PCR (RT-qPCR). We also investigated the potential relationship between tumor LSINCT5 levels and clinicopathological features of gastrointestinal cancer. Finally, we assessed whether LSINCT5 influences in vitro cell proliferation. The expression of LSINCT5 is significantly upregulated in gastrointestinal cancer tissues and cell lines relative to their normal counterparts. In addition, increased LSINCT5 expression was correlated with a larger tumor size, deeper tumor depth, and advanced clinical stage. Kaplan-Meier analysis indicated that gastric cancer (GC) and colorectal cancer (CRC) patients with higher LSINCT5 expression levels have worse disease-free survival (DFS) and disease-specific survival (DSS) rates. Moreover, multivariate analysis revealed that increased expression of LSINCT5 is an independent predictor of DFS and DSS rates in GC patients. The ectopic expression of LSINCT5 in gastrointestinal cancer cell lines resulted in an increase in cellular proliferation; conversely, knock down of LSINCT5 significantly inhibited proliferation. These results suggest that LSINCT5 may represent a novel prognostic indicator and a target for gene therapy in gastrointestinal cancer.


A New RF Heating Strategy for Thermal Treatment of Atherosclerosis.
Restenosis remains a challenge for the treatment of atherosclerosis due to the damage of the endothelial layer and induced proliferation of the smooth muscle cell. A new RF heating strategy was proposed to selectively ablate the atherosclerosis plaque, and to thermally inhibit the proliferation of smooth muscle cells, while keeping the endothelial cells intact. To achieve the goal, an internal cooling agent and distributed electrodes have been integrated in the new designed balloon catheter to focus the shape conformal energy onto the plaque shape. A three-dimensional (3-D) model with experimentally fitted parameters has been established to demonstrate the heating ability of the design and evaluate the microelectrodes configurations for different plaque geometries. The 3-D shape of the lesions resulting from different electrodes settings is obtained. It is found that by individual control of the micro-electrodes, special shapes of the lesions can be formed, which can match the eccentric crescent plaques. Besides, through changing of the polarity of the electrodes, separate lesions can be reached. This suggests the possibility for treatment of disconnected plaques in situ. By the control of RF heating and convection coefficient of the internal cooling agent, a targeted heating region away from the inner surface of the blood vessel can be realized. This study has illustrated the possibility of achieving a precision thermal treatment of atherosclerosis in favor of inhibiting further restenosis.


Discovery of an Inducible Toluene Monooxygenase That Cooxidizes 1,4-Dioxane and 1,1-Dichloroethylene in Propanotrophic Azoarcus sp. Strain DD4.
Cometabolic degradation plays a prominent role in bioremediation of commingled groundwater contamination (e.g., chlorinated solvents and the solvent stabilizer 1,4-dioxane [dioxane]). In this study, we untangled the diversity and catalytic functions of multicomponent monooxygenases in Azoarcus sp. strain DD4, a Gram-negative propanotroph that is effective in degrading dioxane and 1,1-dichloroethylene (1,1-DCE). Using a combination of knockout mutagenesis and heterologous expression, a toluene monooxygenase (MO) encoded by the tmoABCDEF gene cluster was unequivocally proved to be the key enzyme responsible for the cometabolism of both dioxane and 1,1-DCE. Interestingly, in addition to utilizing toluene as a primary substrate, this toluene MO can also oxidize propane into 1-propanol. Expression of this toluene MO in DD4 appears inducible by both substrates (toluene and propane) and their primary hydroxylation products (m-cresol, p-cresol, and 1-propanol). These findings coherently explain why DD4 can grow on propane and express toluene MO for active cooxidation of dioxane and 1,1-DCE. Furthermore, upregulation of tmo transcription by 1-propanol underlines the implication potential of using 1-propanol as an alternative auxiliary substrate for DD4 bioaugmentation. The discovery of this toluene MO in DD4 and its degradation and induction versatility can lead to broad applications, spanning from environmental remediation and water treatment to biocatalysis in green chemistry.IMPORTANCE Toluene MOs have been well recognized given their robust abilities to degrade a variety of environmental pollutants. Built upon previous research efforts, this study ascertained the untapped capability of a toluene MO in DD4 for effective cooxidation of dioxane and 1,1-DCE, two of the most prevailing yet challenging groundwater contaminants. This report also aligns the induction of a toluene MO with nontoxic and commercially accessible chemicals (e.g., propane and 1-propanol), extending its implications in the field of environmental microbiology and beyond.


Morphology control in crystalline nanoparticle-polymer aggregates.
Self-assembly of nanoparticles can be mediated by polymers, but has so far led almost exclusively to nanoparticle aggregates that are amorphous. Here, we employed Coulombic interactions to generate a range of composite materials from mixtures of charged nanoparticles and oppositely charged polymers. The assembly behavior of these nanoparticle/polymer composites depends on their order of addition: polymers added to nanoparticles give rise to stable aggregates, but nanoparticles added to polymers disassemble the initially formed aggregates. The amorphous aggregates were transformed into crystalline ones by transiently increasing the ionic strength of the solution. The morphology of the resulting crystals depended on the length of the polymer: short polymer chains mediated the self-assembly of nanoparticles into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer assemblies, within which the crystalline order of nanoparticles was retained.


SEQUENTIAL RADIATIONS AND PATTERNS OF SPECIATION IN THE HAWAIIAN CRICKET GENUS LAUPALA INFERRED FROM DNA SEQUENCES.
The tremendous diversity of endemic Hawaiian crickets is thought to have originated primarily through intraisland radiations, in contrast to an interisland mode of diversification in the native Hawaiian Drosophila. The Hawaiian cricket genus Laupala (family Gryllidae) is one of several native genera of flightless crickets found in rain-forest habitat across the Hawaiian archipelago. I examined the phylogenetic relationships among mitochondrial DNA (mtDNA) sequences sampled from 17 species of Laupala, including the 12S ribosomal RNA (rRNA), transfer RNA (RNA)val and 16S rRNA regions. The distribution of mtDNA variants suggests that species within Laupala are endemic to single islands. The phylogenetic estimate produced from both maximum likelihood and maximum parsimony supports the hypothesis that speciation in Laupala occurred mainly within islands. The inferred biogeographical history suggests that diversification in Laupala began on Kauai, the oldest rain-forested Hawaiian island. Subsequently, colonization to younger islands in the archipelago resulted in a radiation of considerable phylogenetic diversity. Phylogenetic patterns in mtDNA are not congruent with prior systematic or taxonomic hypotheses. Hypotheses that may explain the conflict between the phylogenetic patterns of mtDNA variation and the species taxonomy are discussed.


Prenatal Lipid-Based Nutrient Supplements Do Not Affect Pregnancy or Childbirth Complications or Cesarean Delivery in Bangladesh: A Cluster-Randomized Controlled Effectiveness Trial.
Background: Pregnancy and childbirth complications and cesarean delivery are common in Bangladesh.Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on pregnancy and childbirth complications and cesarean delivery.Methods: We conducted the Rang-Din Nutrition Study, a cluster-randomized controlled effectiveness trial within a community health program in rural Bangladesh. We enrolled 4011 pregnant women in early pregnancy. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing essential fatty acids and 22 vitamins and minerals. Pregnancy and childbirth complications and the cesarean delivery rate were secondary outcomes of the study.Results: Women in the LNS-PL group did not differ significantly from the IFA group with respect to mean systolic blood pressure at 36 wk gestation (113 and 112 mm Hg; P = 0.17), diastolic blood pressure at 36 wk gestation (68.9 and 68.7 mmHg; P = 0.88), or mean total number of pregnancy and childbirth complications (0.32 and 0.31; P = 0.86). They also did not differ significantly with respect to the prevalence of high blood pressure at 36 wk (1.74% and 2.03%; P = 0.62), antepartum hemorrhage (0.83% and 1.39%; P = 0.21), prolonged labor (8.34% and 8.79%; P = 0.68), early rupture of membranes (9.30% and 8.45%; P = 0.43), convulsions (1.57% and 1.08%; P = 0.24), high blood pressure in labor (1.54% and 1.19%; P = 0.46), obstructed labor (2.83% and 2.91%; P = 0.90), any complications during pregnancy or childbirth (35.9% and 37.1%; P = 0.64), episiotomy (6.31% and 6.44%; P = 0.90), or cesarean delivery (15.6% and 14.2%; P = 0.48).Conclusion: Compared with IFA, antenatal LNS-PL did not increase or decrease pregnancy and childbirth complications or cesarean delivery among women in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038.


PPARγ agonist rosiglitazone is neuroprotective after traumatic spinal cord injury via anti-inflammatory in adult rats.
Spinal cord injury (SCI) results in the loss of function below the lesion. Secondary injury following the primary impact includes a number of biochemical and cellular alterations leading to tissue necrosis and cell death. Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated transcription factor of nuclear hormone receptor superfamily. Thiazolidinedione rosiglitazone is a potent agonist of PPARγ which is shown to induce neuroprotection in animal models of focal ischemia and traumatic brain injury. SCI is induced by the application of vascular clips (force of 24 g) to the dura via a four-level T(5)-T(8) laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of rosiglitazone, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) apoptosis (terminal deoxynucleotidyl transferase-mediated UTP end labeling staining and electron microscopy); (4) proinflammatory cytokines TNF-α and IL-β; (5) PPARγ, HSP70 and HSP27 expressions. To elucidate whether the protective effects of rosiglitazone were mediated via the estrogen receptors, we investigated the effect of a PPARγ antagonist, GW9662, on the protective effects of rosiglitazone. GW9662 significantly antagonized the effect of the rosiglitazone and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of rosiglitazone after SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.


Zorrimidazolone, a bioactive alkaloid from the non-indigenous mediterranean stolidobranch Polyandrocarpa zorritensis.
Chemical analysis of the Mediterranean ascidian Polyandrocarpa zorritensis (Van Name 1931) resulted in the isolation of a series of molecules including two monoindole alkaloids, 3-indolylglyoxylic acid (3) and its methyl ester (4), 4-hydroxy-3-methoxyphenylglyoxylic acid methyl ester (1) and a new alkaloid we named zorrimidazolone (2). The structure of the novel compound 2 has been elucidated by spectroscopic analysis and bioactivity of all compounds has been investigated. Zorrimidazolone (2) showed a modest cytotoxic activity against C6 rat glioma cell line.


[Having an Eye for Families? - Standardized Family Diagnostics in Socialpediatric Centres].
Having an Eye for Families? - Standardized Family Diagnostics in Socialpediatric Centres In socialpediatric centres (SPZ) children and adolescents with mental and/or physical disorders/impairments are diagnosed and treated together with their families. This cross-sectional study researches to what extent standardized family diagnostic questionnaires are used in this context. One third of the 152 German SPZ participated in this questionnaire study (N = 50). While nearly all SPZ use intelligence tests (98 %) and symptom questionnaires (100 %) (s. Sydow u. Homes, in prep.), family diagnostic is applied remarkably seldom in German socialpediatric centres up to now: Only 14 of 28 family questionnaires whose use we had evaluated systematically, ever were used by the participating SPZs. Implications for research and clinical practice are derived.


Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.
The use of time series profiling to identify groups of functionally related genes (synexpression groups) is a powerful approach for the discovery of gene function. Here we apply this strategy during Ras(V12) immortalization of Drosophila embryonic cells, a phenomenon not well characterized. Using high-resolution transcriptional time-series datasets, we generated a gene network based on temporal expression profile similarities. This analysis revealed that common immortalized cells are related to adult muscle precursors (AMPs), a stem cell-like population contributing to adult muscles and sharing properties with vertebrate satellite cells. Remarkably, the immortalized cells retained the capacity for myogenic differentiation when treated with the steroid hormone ecdysone. Further, we validated in vivo the transcription factor CG9650, the ortholog of mammalian Bcl11a/b, as a regulator of AMP proliferation predicted by our analysis. Our study demonstrates the power of time series synexpression analysis to characterize Drosophila embryonic progenitor lines and identify stem/progenitor cell regulators.


Differential expression of cathepsins K, S and V between young and aged Caucasian women skin epidermis.
Cutaneous aging translates drastic structural and functional alterations in the extracellular matrix (ECM). Multiple mechanisms are involved, including changes in protease levels. We investigated the age-related protein expression and activity of cysteine cathepsins and the expression of two endogenous protein inhibitors in young and aged Caucasian women skin epidermis. Immunofluorescence studies indicate that the expression of cathepsins K, S and V, as well as cystatins A and M/E within keratinocytes is reduced in photoprotected skin of aged women. Furthermore, the overall endopeptidase activity of cysteine cathepsins in epidermis lysates decreased with age. Albeit dermal elastic fiber and laminin expression is reduced in aged skin, staining of nidogen-1, a key protein in BM assembly that is sensitive to proteolysis by cysteine, metallo- and serine proteases, has a similar pattern in both young and aged skin. Since cathepsins contribute to the hydrolysis and turnover of ECM/basement membrane components, the abnormal protein degradation and deposition during aging process may be related in part to a decline of lysosomal/endosomal cathepsin K, S and V activity.


Determination of Optimized Growth Medium and Cryoprotective Additives to Enhance the Growth and Survival of Lactobacillus salivarius.
The beneficial effects of lactic acid bacteria (LAB) have been intensively investigated in recent decades with special focus on modulation of the host intestinal microbiota. Numerous discoveries of effective probiotics are driven by a significantly increasing demand for dietary supplements. Consequently, technological advances in the large-scale production and lyophilization are needed by probiotic-related industries for producing probiotic LAB for commercial use. Our study had a dual objective, to determine the optimum growth medium composition and to investigate appropriate cryoprotective additives (CPAs) for Lactobacillus salivarius, and compare its responses with other Lactobacillus species. The one-factor-at-a-time method and central composite design were applied to determine the optimal medium composition for L. salivarius cultivation. The following composition of the medium was established (per liter): 21.64 g maltose, 85 g yeast extract, 1.21 ml Tween 80, 6 g sodium acetate, 0.2 g MgSO₄∙7H₂O, 0.02 g MnSO₄∙H₂O, 1 g K₂HPO₄, 1.5 g KH₂PO₄, 0.01 g FeSO₄∙7H₂O, and 1 g sodium citrate. A cryoprotective additive combination comprising 10% (w/v) skim milk and 10% (w/v) sucrose supplemented with 2.5% (w/v) sodium glutamate was selected for L. salivarius, and its effectiveness was confirmed using culture-independent methods in the freeze-dried cells of the Lactobacillus strains. In conclusion, the optimized medium enhanced the species-specific cultivation of L. salivarius. On the other hand, the cryoprotective effects of the selected CPA mixture may also be dependent on the bacterial strain. This study highlights the necessity for precise and advanced processing techniques for large-scale production of probiotics in the food and feed industries.


Body mass index and height in relation to type 2 diabetes by levels of intelligence and education in a large cohort of Danish men.
Socioeconomic status (SES) is inversely associated with risks of type 2 diabetes (T2D). We investigated if young men's cognitive function, measured by intelligence test scores and educational level, as determinants of SES modified associations between body mass index (BMI) and height with the risk of T2D. 369 989 young men from the Danish Conscription Database born between 1939 and 1959 with information on measured height, weight, intelligence test scores, and education were linked to the Danish National Patient Register. During follow-up from 1977 through 2015, T2D was recorded in 32 188 men. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regressions. BMIs below-average (z-scores ≤ 0) were not related to risks of T2D. For BMIs above-average (z-scores > 0), positive associations between BMI and T2D were slightly stronger among men with higher intelligence test scores or longer educations than among men with lower levels of these factors (pinteraction-values < 0.004). Irrespective of BMI, incidence rates of T2D were higher among men with low levels of intelligence test score and education. Height was inversely associated with T2D (per z-score, HR = 0.96 (95% CI 0.95-0.97) and the association did not vary by intelligence test scores or education (all pinteraction-values > 0.59). While below-average BMI was not associated with T2D risk, above-average BMIs were and these association were stronger among men with high cognitive function. Nevertheless, T2D risk was higher at lower levels of cognitive function throughout the range of BMI. Height was inversely associated with T2D and it was not modified by cognitive function.


Practices and exploration on competition of molecular biological detection technology among students in food quality and safety major.
With the increasing importance in the application of the molecular biological detection technology in the field of food safety, strengthening education in molecular biology experimental techniques is more necessary for the culture of the students in food quality and safety major. However, molecular biology experiments are not always in curricula of Food quality and safety Majors. This paper introduced a project "competition of molecular biological detection technology for food safety among undergraduate sophomore students in food quality and safety major", students participating in this project needed to learn the fundamental molecular biology experimental techniques such as the principles of molecular biology experiments and genome extraction, PCR and agarose gel electrophoresis analysis, and then design the experiments in groups to identify the meat species in pork and beef products using molecular biological methods. The students should complete the experimental report after basic experiments, write essays and make a presentation after the end of the designed experiments. This project aims to provide another way for food quality and safety majors to improve their knowledge of molecular biology, especially experimental technology, and enhances them to understand the scientific research activities as well as give them a chance to learn how to write a professional thesis. In addition, in line with the principle of an open laboratory, the project is also open to students in other majors in East China University of Science and Technology, in order to enhance students in other majors to understand the fields of molecular biology and food safety. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(4):343-350, 2017.


Comparisons of plasma aldosterone and renin data between an automated chemiluminescent immunoanalyzer and conventional radioimmunoassays in the screening and diagnosis of primary aldosteronism.
Determining values of plasma renin activity (PRA) or plasma active renin concentration (ARC), plasma aldosterone concentration (PAC), and aldosterone-to-renin ratio (ARR) is essential to diagnose primary aldosteronism (PA), but it takes several days with conventional radioimmunoassays (RIAs). Chemiluminescent enzyme immunoassays for PAC and ARC using the Accuraseed® immunoanalyzer facilitated the determination, but relations between Accuraseed® immunoanalyzer-based and RIA-based values in samples of PA confirmatory tests and adrenal venous sampling remained to be elucidated. We addressed this issue in the present study. This is a prospective, cross-sectional study. ARC and PAC values were measured by the Accuraseed® immunoanalyzer in samples, in which PRA and PAC values had been measured by the PRA-FR® RIA and SPAC®-S Aldosterone kits, respectively. The relations between Accuraseed® immunoanalyzer-based and RIA-based values were investigated with regression analyses. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was determined by the receiver operating characteristic analysis. After log-log transformations, linear relations with high coefficients of determination were observed between Accuraseed® immunoanalyzer-based and RIA-based data of renin and aldosterone. Following the PA guidelines of Japan Endocrine Society, Accuraseed® immunoanalyzer-based cutoffs were calculated from the regression equations: the basal PAC for PA screening >12 ng/dL, PAC for the saline infusion test >8.2 ng/dL, ARC for the furosemide-upright test <15 pg/mL, and ARR for the captopril challenge test >3.09 ng/dL per pg/mL. The optimal cutoff of Accuraseed® immunoanalyzer-based ARR for PA screening was >2.43 ng/dL over pg/mL not to overlook bilateral PA patients. The present study provided conversion formulas between Accuraseed® immunoanalyzer-based and RIA-based values of renin, aldosterone, and ARR, not only in basal samples but also in samples of PA confirmatory tests and adrenal venous sampling. Although validation studies are awaited, the present study will become priming water of harmonization of renin and aldosterone immunoassays.


Respiratory muscle strength in the physically active elderly.
Advancing age is associated with a decline in the strength of the skeletal muscles, including those of respiration. Respiratory muscles can be strengthened with nonrespiratory activities. We therefore hypothesized that regular exercise in the elderly would attenuate this age-related decline in respiratory muscle strength. Twenty-four healthy subjects older than 65 years were recruited (11 males and 13 females). A comprehensive physical activity survey was administered, and subjects were categorized as active (n = 12) or inactive (n = 12). Each subject underwent testing of maximum inspiratory and expiratory pressures (PI(max) and PE(max)). Diaphragmatic thickness (tdi) was measured via two-dimensional B-mode ultrasound. There were no significant differences between the active and inactive groups with respect to age (75 vs. 73 years) or body weight (69.1vs. 69.9 kg). There were more women (9) than men (3) in the inactive group. Diaphragm thickness was greater in the active group (0.31 +/- 0.06 cm vs. 0.25 +/- 0.04 cm; p = 0.011). PE(max) and PI(max) were also greater in the active group (130 +/- 44 cm H(2)O vs. 80 +/- 24 cm H(2)O; p = 0.002; and 99 +/- 32 cm H(2)O vs. 75 +/- 14 cm H(2)O; p = 0.03). There was a positive association between PI(max )and tdi (r = 0.43, p = 0.03). Regular exercise was positively associated with diaphragm muscle thickness in this cohort. As PE(max) was higher in the active group, we postulate that recruitment of the diaphragm and abdominal muscles during nonrespiratory activities may be the source of this training effect.


Gimap5-dependent inactivation of GSK3β is required for CD4+ T cell homeostasis and prevention of immune pathology.
GTPase of immunity-associated protein 5 (Gimap5) is linked with lymphocyte survival, autoimmunity, and colitis, but its mechanisms of action are unclear. Here, we show that Gimap5 is essential for the inactivation of glycogen synthase kinase-3β (GSK3β) following T cell activation. In the absence of Gimap5, constitutive GSK3β activity constrains c-Myc induction and NFATc1 nuclear import, thereby limiting productive CD4+ T cell proliferation. Additionally, Gimap5 facilitates Ser389 phosphorylation and nuclear translocation of GSK3β, thereby limiting DNA damage in CD4+ T cells. Importantly, pharmacological inhibition and genetic targeting of GSK3β can override Gimap5 deficiency in CD4+ T cells and ameliorates immunopathology in mice. Finally, we show that a human patient with a GIMAP5 loss-of-function mutation has lymphopenia and impaired T cell proliferation in vitro that can be rescued with GSK3 inhibitors. Given that the expression of Gimap5 is lymphocyte-restricted, we propose that its control of GSK3β is an important checkpoint in lymphocyte proliferation.


Treatment of metastatic colorectal cancer with hepatic artery combination chemotherapy.
Treatment of patients with hepatic metastases from colorectal cancer using hepatic artery floxuridine (FUDR) has been reported to induce high partial remission rates and perhaps prolonged survival. However, several investigators, including our own group, have obtained response rates of only 30%. Alkylating agents can increase the efficacy of antimetabolites. Based on clinical data and pharmacokinetic considerations the authors have combined FUDR with mitomycin C and carmustine (BCNU) by the arterial route. Thirty-six patients with hepatic metastases from colorectal cancer received FUDR 0.3 mg/kg/day 2 weeks of 4, mitomycin C 15 mg/M2 over 1 hour every 8 weeks, and BCNU 150 mg/M2 over 1 hour every 8 weeks--all via the hepatic artery using Infusaid pumps (Infusaid, Sharon, MA). The mitomycin C and BCNU were alternated monthly at the start of each FUDR cycle. The patient characteristics were as follows: 78% hepatomegaly, 44% also extrahepatic tumor, 42% prior systemic 5-fluorouracil. Combined partial and complete response rates were independent of prior chemotherapy: 71% if untreated, 67% with prior 5-fluorouracil. Median survival for the combined response/stable disease group was 13.7 months from the start of hepatic artery chemotherapy, and 4.5 months for the six nonresponders. Based on these data the authors have begun a randomized trial comparing single-agent FUDR to the FUDR, mitomycin C, BCNU combination.