Type II phosphatidylinositol 4-kinase β is an integral signaling component of early T cell activation mechanisms.
The early signaling events in T cell activation through CD3 receptor include a rapid change in intra cellular free calcium concentration and reorganization of actin cytoskeleton. Phosphatidylinositol 4-kinases (PtdIns 4-kinases) are implicated as key components in these early signaling events. The role of type II PtdIns 4-kinase β in CD3 receptor signaling was investigated with the help of short hairpin RNA sequences. Cross-linking of CD3 receptors on Jurkat T Cells with monoclonal antibodies showed an early increase in type II PtdIns 4-kinase activity and co-localization of type II PtdIns 4-kinase β with CD3 ζ. Transfection of Jurkat T Cells with shRNAs inhibited CD3 receptor mediated type II PtdIns 4-kinase activation with a concomitant reduction in intra cellular calcium release, suggesting a role for type II PtdIns 4-kinase β in CD3 receptor signal transduction. Knock-down of type II PtdIns 4-kinase β with shRNAs also correlated with a decrease in PtdIns 4-kinase activity in cytoskeleton fractions and reduced adhesion to matrigel surfaces. These results indicate that type II PtdIns 4-kinase β is a key component in early T cell activation signaling cascades.


Gamma-radiation-induced chromosomal aberrations in human lymphocytes: dose-rate effects in stimulated and non-stimulated cells.
Stimulated and non-stimulated human peripheral blood lymphocytes were irradiated acutely and chronically, over 24 h. Dose-effect relationships for dicentric chromosomes were established and various models were fitted to the data. At prolonged irradiations the yield decreased in basic agreement with the linear-quadratic model of abberration induction. Dose-protraction experiments of PHA+ and PHA- lymphocytes, irradiated under various conditions of oxygenation and suspension (culture medium, whole blood) showed that the rejoining time increased from about 3 h in non-stimulated cells to about 10 h after PHA stimulation, and that this retarded rejoining was most likely due to blastic transformation itself and not to other conditions of irradiation.


Relatives and patients as partners in the management of schizophrenia. The development of a service model.
Considerable advances have been made in the family management of schizophrenia but there remains a major challenge for the psychiatric services to integrate these innovations into clinical practice. A number of important issues need to be considered in developing routine clinical services: the problem of engaging families in a therapeutic programme; the utility of the concept of 'expressed emotion'; and procedures for clinical practice. The latter include the needs of low-EE families; maintaining quality of intervention in a clinical context; responding to the multiplicity of needs of the patient and family; and integrating family interventions with ongoing rehabilitation practice. A model of service provision is described.


Atypical mycobacterial infection of intraparotid lymph nodes. Clinical and sialographic observations.
Four children are reported with a chronic caseating granulomatous infection on the intraparotid lymph nodes most likely due to atypical mycobacteria. The sialogram showed one or more masses within the parotid gland.


Health-related quality of life among persons with initial mild, moderate, and severe or critical COVID-19 at 1 and 12 months after infection: a prospective cohort study.
Currently, there is limited evidence about the long-term impact on physical, social and emotional functioning, i.e. health-related quality of life (HRQL) after mild or moderate COVID-19 not requiring hospitalization. We compared HRQL among persons with initial mild, moderate or severe/critical COVID-19 at 1 and 12 months following illness onset with Dutch population norms and investigated the impact of restrictive public health control measures on HRQL. RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled adult participants after confirmed SARS-CoV-2 diagnosis. HRQL was assessed with the Medical Outcomes Study Short Form 36-item health survey (SF-36). SF-36 scores were converted to standard scores based on an age- and sex-matched representative reference sample of the Dutch population. Differences in HRQL over time were compared among persons with initial mild, moderate or severe/critical COVID-19 using mixed linear models adjusted for potential confounders. By December 2021, 349 persons were enrolled of whom 269 completed at least one SF-36 form (77%). One month after illness onset, HRQL was significantly below population norms on all SF-36 domains except general health and bodily pain among persons with mild COVID-19. After 12 months, persons with mild COVID-19 had HRQL within population norms, whereas persons with moderate or severe/critical COVID-19 had HRQL below population norms on more than half of the SF-36 domains. Dutch-origin participants had significantly better HRQL than participants with a migration background. Participants with three or more COVID-19 high-risk comorbidities had worse HRQL than part participants with fewer comorbidities. Participants who completed the SF-36 when restrictive public health control measures applied reported less limitations in social and physical functioning and less impaired mental health than participants who completed the SF-36 when no restrictive measures applied. Twelve months after illness onset, persons with initial mild COVID-19 had HRQL within population norms, whereas persons with initial moderate or severe/critical COVID-19 still had impaired HRQL. Having a migration background and a higher number of COVID-19 high-risk comorbidities were associated with worse HRQL. Interestingly, HRQL was less impaired during periods when restrictive public health control measures were in place compared to periods without.


Organization of anterogradely labeled spinocervical tract terminations in the lateral cervical nucleus of the cat.
The anterograde transport of horseradish peroxidase following injections into the cervical, thoracic, or lumbosacral spinal cord was used to examine the organization of spinocervical tract terminations in the lateral cervical nucleus (LCN) of the cat. A somatotopic organization of the labeling originating from different spinal levels was observed in the mediolateral dimension. Cervical labeling generally occurred in the ventromedial portion and lumbosacral labeling in the dorsolateral portion of the LCN. Thoracic labeling occurred both in the middle and the most lateral edge of the nucleus. In all cases, labeling was distributed over most of the rostrocaudal extent of the LCN. In addition, distinct patches of labeling were present in the medialmost portion of the nucleus, regardless of the spinal level injected. These observations corroborate the topographical organization of the LCN described previously on the basis of physiological and retrograde labeling data, and support the identification of the medialmost part of the LCN as a distinct portion of the nucleus. Terminal labeling in the LCN always occurred in multiple, longitudinally distributed fields. The afferent input to each terminal field coursed in separate, loose bundles of fibers that descended from the superficial dorsolateral funiculus. Large injections resulted in more extensive, overlapping terminal fields. These observations indicate that collateral projections result in several discrete representations of a given portion of the skin over the longitudinal extent of the LCN, but that topographical relationships are longitudinally maintained. It is suggested that these multiple terminal fields are the anatomical correlate of the functionally selective convergence of spinocervical tract terminations, that has previously been postulated on physiological grounds to explain the generation of LCN receptive fields with homogenous receptor input within a somatotopic framework.


Impact of belatacept and tacrolimus on cytomegalovirus viral load control and relapse in moderate and high-risk cytomegalovirus serostatus kidney transplant recipients.
Belatacept improves long-term graft survival, but control of some primary viral infections may be impaired. We evaluated the impact of belatacept and tacrolimus on cytomegalovirus (CMV) viral control, remission and relapse in CMV high-risk and moderate-risk recipients. Using a multistate Markov model, we evaluated viral load state transitions of 173 kidney transplant recipients with at least one episode of viremia within 1 year after transplant: state 1, undetectable/low viral load; state 2, moderate viremia; and state 3, severe viremia. Among high-risk recipients, belatacept-treated recipients exhibited a significantly higher probability of entering moderate viremia (.36; 95% CI = .31, .41) than tacrolimus-treated recipients (.20; 95% CI = .13, .29). The expected number of days in viremic states differed. High-risk belatacept-treated recipients persisted in moderate viremia for significantly longer (128 days, 95% CI = 110, 146) than did tacrolimus-treated recipients (70.0 days, 95% CI = 45.2, 100) and showed a trend of shorter duration in low/undetectable viral load state (172 days, 95% CI = 148, 195) than did tacrolimus-treated recipients (239 days, 95% CI = 195, 277). Moderate-risk recipients showed better viral load control and with no differences by immunosuppression. High-risk belatacept-treated recipients showed defects in sustaining viral control relative to tacrolimus-treated recipients. Avoidance of initial use belatacept in high-risk recipients or development of modified management protocols should be considered.


The effect of fatty diacid acylation of human PYY3-36 on Y2 receptor potency and half-life in minipigs.
Peptides are notoriously known to display very short in vivo half-lives often measured in minutes which in many cases greatly reduces or eliminates sufficient in vivo efficacy. To obtain long half-lives allowing for up to once-weekly dosing regimen, fatty acid acylation (lipidation) have been used to non-covalently associate the peptide to serum albumin thus serving as a circulating depot. This approach is generally considered in the scientific and patent community as a standard approach to protract almost any given peptide. However, it is not trivial to prolong the half-life of peptides by lipidation and still maintain high potency and good formulation properties. Here we show that attaching a fatty acid to the obesity-drug relevant peptide PYY3-36 is not sufficient for long pharmacokinetics (PK), since the position in the backbone, but also type of fatty acid and linker strongly influences PK and potency. Furthermore, understanding the proteolytic stability of the backbone is key to obtain long half-lives by lipidation, since backbone cleavage still occurs while associated to albumin. Having identified a PYY analogue with a sufficient half-life, we show that in combination with a GLP-1 analogue, liraglutide, additional weight loss can be achieved in the obese minipig model.


[Histological diagnosis of lung bacterial necrotizing infections: a study of four fulminant cases].
We report the clinical and histopathological features of four cases of pulmonary bacterial infections associated with extensive necrosis, which were fatal within a few hours (two cases of group A Streptococcus, one case of Staphyloccocus aureus and one case of Haemophilus influenzae infection). These bacterial infections are extremely severe conditions due to the production of necrotizing toxins. Histological findings are distinctive, showing extensive hemorrhagic necrosis, widespread layers of bacteria, and very few or no inflammatory cell components. These dramatic infections are extremely rare, occuring with no apparent underlying disease, both in immunodeficient and immunocompetent patients. The main differential diagnosis is a viral infection, difficult to diagnose on histological examination alone. The diagnosis is based on histological and microbiological results.


Asymmetric Intermolecular Heck Reaction of Propargylic Acetates and Cycloalkenes to Access Fused Cyclobutenes.
An asymmetric Heck annulation of propargylic acetates with several types of cyclic olefins affords highly strained cyclobutenes in high enantioselectivity.


The Genetics of Hidradenitis Suppurativa.
A family history of hidradenitis suppurativa (HS) is reported by about one-third of patients, and the pattern of inheritance suggests a single gene disorder inherited as an autosomal dominant trait. Several γ-secretase gene mutations were identified in 6 Han Chinese families with multiple affected family members. Several of the Han Chinese patients had a severe disease phenotype, with involvement of nonflexural skin locations such as the back and chest. These findings have been repeated in other populations, but γ-secretase mutations have been found only in a minority of patients with HS.


Development, validation and reliabilty of a questionnaire to evaluate the changes on the level of physical exercises and in daily life habits due to COVID-19 pandemic social distancing.
Physical inactivity is expected to happen during the COVID-19 pandemic through home quarantine measures. The aim of this study was to develop, validate and perform the reliability of the questionnaire "Physical exercise (PE) level before and during social isolation (PEF-COVID19)" to evaluate the level of PE during the social distancing due to the COVID-19 pandemic and to try to identify changes in the daily life of the individuals. This transversal study was developed to measure psychometric properties of the questionnaire PEF-COVID19. The survey was divided into 4 sections including subjects' characterization, social isolation update and physical exercise performed, pain, anxiety and stress before and during COVID-19 pandemic. After the survey construction in Portuguese language (Brazil), the survey was transferred to an online digital platform (Google® forms). The Construct, Clarity and Relevance Validation strategy was judged by a panel of experts and the validity index (VI) were calculated. The reliability was evaluated through the test-retest interrater reliability and measured through the intraclass correlation coefficient (ICC) and Kappa coefficient (KC). Twenty-five experts participated of the survey validity and 34 respondents from the target population participated of the test-retest reliability. The general average measures for VI were all above 0.84 and test-retest ICC and KC were 0.89 and 0.88, respectively. This survey was considered valid and reliable to be applied to the general population over 18 years-old to investigate the PE practice and psychological aspects during the social distancing due to the COVID-19 pandemic, a public health problem.


Prognostic impact of comorbidities in hospitalized patients with acute exacerbation of chronic heart failure.
To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF). 1119 patients admitted for AE-CHF and with NT-proBNP levels >900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality. During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p<.001), and anemia (p<.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission. Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions.


LAST-seq: single-cell RNA sequencing by direct amplification of single-stranded RNA without prior reverse transcription and second-strand synthesis.
Existing single-cell RNA sequencing (scRNA-seq) methods rely on reverse transcription (RT) and second-strand synthesis (SSS) to convert single-stranded RNA into double-stranded DNA prior to amplification, with the limited RT/SSS efficiency compromising RNA detectability. Here, we develop a new scRNA-seq method, Linearly Amplified Single-stranded-RNA-derived Transcriptome sequencing (LAST-seq), which directly amplifies the original single-stranded RNA molecules without prior RT/SSS. LAST-seq offers a high single-molecule capture efficiency and a low level of technical noise for single-cell transcriptome analyses. Using LAST-seq, we characterize transcriptional bursting kinetics in human cells, revealing a role of topologically associating domains in transcription regulation.


Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study.
Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery.


Shunt Catheter Migration Due to Negative Thoracic Pressure.
Permanent cerebrospinal fluid diversion has a lengthy list of complications. We present an unusual clinical image of shunt catheter migration. A 54-year-old female had a history of subarachnoid hemorrhage that resulted in communicating hydrocephalus, which needed a ventriculoperitoneal shunt placement. On outpatient follow-up, she was found to have a sunken skin flap that was resistant to raising the shunt valve setting. A radiograph of the shunt system revealed that the peritoneal catheter had migrated into the thoracic cavity. On review of the patient's previous imaging, an area indicative of a minor pleural breach was identified that exposed the catheter to the negative thoracic pressure, which resulted in progressive catheter migration. The patient then underwent removal of the shunt system since her hydrocephalus had resolved. A pleural breach during shunt placement can result in the migration of the shunt catheter into the thoracic cavity under the effect of negative thoracic pressure.


Role of the basal ganglia in the control of sleep and wakefulness.
The basal ganglia (BG) act as a cohesive functional unit that regulates motor function, habit formation, and reward/addictive behaviors, but the debate has only recently started on how the BG maintain wakefulness and suppress sleep to achieve all these fundamental functions of the BG. Neurotoxic lesioning, pharmacological approaches, and the behavioral analyses of genetically modified animals revealed that the striatum and globus pallidus are important for the control of sleep and wakefulness. Here, we discuss anatomical and molecular mechanisms for sleep-wake regulation in the BG and propose a plausible model in which the nucleus accumbens integrates behavioral processes with wakefulness through adenosine and dopamine receptors.


Steam and air co-injection in removing residual TCE in unsaturated layered sandy porous media.
Steam and air co-injection is a promising technique for volatile and semi-volatile organic contaminant remediation in heterogeneous porous media. In this study, removal of trichloroethene (TCE) with steam-air co-injection was investigated through a series of 2D sandbox experiments with different layered sand structures, and through numerical simulations. The results show that a layered structure with coarse sand, in which steam and air convection are relatively rapid, resulted in a higher removal rate and a larger removal ratio than those observed in an experiment using finer sand; however, the difference was not significant, and the removal ratios from three experiments ranged from 85% to 94%. Slight downward movement of TCE was observed for Experiment 1 (TCE initially in a fine sand zone encased in a coarse sand), while no such movement was observed for Experiment 2 (TCE initially in two fine sand layers encased in a coarse sand) or 3 (TCE initially in a silty sand zone encased in a coarse sand). Simulations show accumulation of TCE at the interface of the layered sands, which indicates a capillary barrier effect in restraining the downward movement of TCE. This effect is illustrated further by a numerical experiment with homogeneous coarse sand, in which continuous downward TCE movement to the bottom of the sandbox was simulated. Another numerical experiment with higher water saturation was also conducted. The results illustrate a complicated influence of water saturation on TCE removal in a layered sand structure.


Outcomes of Zone 3 Open Globe Injuries by Wound Extent: Subcategorization of Zone 3 Injuries Segregates Visual and Anatomic Outcomes.
Open globe injuries (OGIs) are categorized by zone, with zone 3 (Z3) comprising wounds > 5 mm beyond the limbus. Outcomes of Z3 OGIs are highly heterogeneous. Open globe injuries with far posterior Z3 (pZ3) wounds were hypothesized to have worse visual and anatomic outcomes. Single-center retrospective cohort study. A total of 258 eyes with Z3 OGIs. A retrospective review of Z3 OGIs treated at a tertiary center over 12 years. Wounds ≥ 10 mm posterior to the limbus were defined as pZ3. Outcomes were compared between pZ3 and anterior Z3 (aZ3) eyes. Visual acuity on a logarithm of the minimum angle of resolution (logMAR) scale. Secondary outcomes included anatomic outcomes, development of retinal detachment and proliferative vitreoretinopathy, and the number of secondary surgeries. A total of 258 Z3 OGI eyes with > 30 days follow-up were assessed; 161 (62%) were pZ3. At 3-month follow-up, pZ3 OGIs were more likely to exhibit no light perception (pZ3: 38%; aZ3: 17%; P < 0.003), lack count fingers vision (pZ3: 72%; aZ3: 43%; P < 0.002), and fail to read a letter on the eye chart (pZ3: 83%; aZ3: 64%; P < 0.001). The visual acuity distribution at 3 months was significantly worse for pZ3 compared with aZ3 injuries (P < 0.004). Similar results were found at final follow-up. Multiple linear regression showed that pZ3 location was independently associated with worse visual acuity (β = 0.29, 95% confidence interval [CI], 0.09-0.50, P < 0.006) in addition to presenting acuity, age, vitreous hemorrhage, uveal prolapse, and afferent pupillary defect. Far posterior wounds injuries were more likely to develop retinal detachments (pZ3: 87%; aZ3: 71%; P < 0.01) and proliferative vitreoretinopathy (pZ3 66%; aZ3 47%; P < 0.03). Patients with pZ3 OGIs were significantly more likely to reach poor anatomic outcome (phthisis, enucleation, need for keratoprosthesis) compared with patients with aZ3 OGI (pZ3: 56%; aZ3: 40%; P < 0.03). Posterior OGI extension independently portends worse visual and anatomic outcomes. The effect on visual outcome was durable and clinically relevant compared with established predictors of OGI outcomes. Application of these findings improves the prognostic precision and will guide future research efforts to optimize surgical decision-making in severe OGI cases. Proprietary or commercial disclosure may be found after the references.


The Academy of Dental Materials: Providing roots and wings.
The long history of the Academy of Dental Materials (ADM) is documented with its strategies (a) to rapidly communicate science among its members, (b) to establish special awards to stimulate new science, and (c) to develop new dental materials scientists. We searched the history of the last 35 years of the ADM newsletters, transactions, journals, and officer notes. We document the (a) presidents, (b) meeting history, (c) membership growth, and (d) development of special awards through 2019 with the recent creation of the ADM Marshall Post-Doctoral Award. There are 36 years of recent ADM history, 42 international meetings, membership growth to 400 individuals from 15 countries, service of 19 presidents, Paffenbarger annual Awardees since 1989, induction of >200 fellows, and recognition of the first winner of Marshall Post-Doctoral Award in 2018. New directions for recruiting members are suggested. Three potential new thrusts for the organization are presented: artificial intelligence, genetic engineering, and intensive member mentoring. These suggestions for the ADM provide a path for the ADM to continue to adapt to the ever changing scientific landscape.


Validation of new real-time polymerase chain reaction assays for detection of hepatitis A virus RNA and parvovirus B19 DNA.
To meet European guidelines for plasma for fractionation, plasma fractionators have implemented parvovirus B19 (B19V) and hepatitis A virus (HAV) nucleic acid test (NAT) screening on test pools. In this study we evaluate recently developed in-house NAT assays for B19V DNA and HAV RNA. The B19V NAT was designed to target two different regions of the B19V genome. The B19V DNA and HAV RNA tests were validated according to commonly used guidelines. The performance of the B19V and HAV assays was evaluated during routine screening of more than 2 × 10(6) donations. The 95% lower limit of detection (LLD) of the HAV NAT was 1.34 IU/mL. The 95% LLD for B19V was 39.1 IU/mL for the NS1 region and 76.9 IU/mL for the VP2 region. The B19V test showed good accuracy, precision, robustness, and no cross-contamination was observed. Both assays detected B19V Genotypes 1 to 3 and HAV Genotypes I to III. During routine screening 103 donations showed B19V DNA loads of more than 1.25 × 10(6) IU/mL and one donation was reactive in the HAV NAT. The dual-target B19V polymerase chain reaction (PCR) showed good accuracy (<0.1 log IU/mL) at the crucial concentration of 10 IU/µL for the NS1 and the VP2 region of the B19V genome and detected all known genotypes with similar sensitivity for each genotype. In addition, the dual target format reduces the chance that molecular variants of B19V are wrongly quantified. The HAV RNA assay showed high sensitivity for Genotypes I to III. Both new PCR assays have been successfully introduced for plasma screening in test pools of 480 or 96 donations.


Photolysis of diacyl peroxides: a radical-based approach for the synthesis of functionalized amino acids.
[reaction: see text] Photolysis of the amino acid derived symmetrical and unsymmetrical diacyl peroxides at 254 nm at low temperature (-78 to -196 degrees C) generates various bis(amino acids) in a concise manner and with orthogonal protection. The methodology was applied to the synthesis of (4R)-5-propyl-L-leucine (PrLeu), a component of HUN-7293.


Enzymatic degradation protects neurons from glutamate excitotoxicity.
Several enzymes with the capacity to degrade glutamate have been suggested as possible neuroprotectants. We initially evaluated the kinetic properties of glutamate pyruvate transaminase (GPT; also known as alanine aminotransferase), glutamine synthetase, and glutamate dehydrogenase under physiologic conditions to degrade neurotoxic concentrations of glutamate. Although all three enzymes initially degraded glutamate rapidly, only GPT was able to reduce toxic (500 microM) levels of glutamate into the physiologic (<20 microM) range. Primary cultures of fetal murine cortical neurons were subjected to paradigms of either exogenous or endogenous glutamate toxicity to evaluate the neuroprotective value of GPT. Neuronal survival after exposure to added glutamate ranging from 100 to 500 microM was improved significantly in the presence of GPT (> or =1 U/ml). Cultures were also exposed to the glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), which produces neuronal injury by elevating extracellular glutamate. GPT significantly reduced the toxicity of PDC. This reduction was associated with a reduction in the PDC-dependent rise in the medium concentration of glutamate. These results suggest that enzymatic degradation of glutamate by GPT can be an alternative to glutamate receptor blockade as a strategy to protect neurons from excitotoxic injury.


Wicking of light hydrophobic liquid phase from water by pulverized rubber: Theoretical and experimental analyses.
Pulverized rubber (PR) can be utilized for capturing floating oils to prevent spreading and volatilization of hydrocarbons. Experiments were conducted using PR with four different particle sizes (ranging from 0.075 to 0.600mm) and South Louisiana crude oil. The oil capture performance of the PR particles was compared with that of powdered activated carbon (AC). Oil-particle interactions were analyzed using capillary theories for lateral aggregation and wicking processes, as well as sorption capacity in relation to particle size. The sorption capacity (as oil to sorbent ratio) for PR with particle size 0.115mm (4.41g/g) was comparable to that of AC with particle size 0.187mm (5.00g/g). Sorption efficiency (oil:powder ratio, g/g) of the PR increased with decreasing particle size. Sorption of oil by PR occurred rapidly (in less than 10min) which indicated strong capillary action. No additional sorption occurred after 30min. For the PR sample with larger particle size (0.600-0.400mm), lateral aggregation was clearly noticeable. The PR-oil aggregates could be easily removed from the water surface without breaking. The cost, availability and recycling potential of PR make it a feasible alternative material for oil spill response and industrial applications which require removal of floating oils.


The effect of betamethasone on neonatal neutrophil chemotaxis.
Antenatal maternal glucocorticoid administration has been widely used to accelerate fetal lung maturation. Glucocorticoids have also been used postnatally in selected neonates as antiinflammatory agents. Numerous studies have shown that glucocorticoids inhibit multiple components of the immune system including neutrophil (PMN) function in children and adults. Since PMNs are of critical importance in host defense against bacterial infection, impaired PMN function in newborn infants is thought to be an important cause of their increased morbidity and mortality from bacterial infection. Further compromise of neonatal PMN function by exogenous factors such as glucocorticoids may therefore be of significant clinical importance. A micropore filter chemotactic assay was used to determine the in vitro effect of betamethasone on the random migration and directed migration (chemotaxis) of PMNs from 18 neonates. The addition of a concentration of betamethasone (0.01 microgram/ml) similar to that found in cord blood following a standard dose administered to the mother resulted in a significant (p less than 0.01) inhibition in mean neonatal PMN random migration (-15.0 +/- 0.8%) and chemotaxis (-23.5 +/- 3.0%). A similar inhibition was not found when PMNs from 14 adults were exposed to the same concentrations of betamethasone. Betamethasone administration to pregnant women or their newborn infants may further impair PMN motility and lead to an increased morbidity and mortality from bacterial infection in neonates.


Biotransformation of 11-keto-β-boswellic acid by Cunninghamella blakesleana.
11-Keto-β-boswellic acid (KBA), as one of the active constituents in the gum resin of Boswellia serrata, possesses significant biological activities including anti-inflammatory activity. However, its extensive metabolism and low polarity has limited the systemic availability of KBA. The present research was aimed to obtain and explore the various possible derivatives of KBA through biotransformation by Cunninghamella blakesleana AS 3.970. A total of ten transformed compounds were isolated and purified, and their chemical structures were characterized as 7β-hydroxy-11-keto-β-boswellic acid; 7β, 15α-dihydroxy-11-keto-β-boswellic acid ; 7β, 16β-dihydroxy-11-keto-β-boswellic acid; 7β, 16α-dihydroxy-11-keto-β-boswellic acid; 7β, 22β-dihydroxy-11-keto-β-boswellic acid; 7β, 21β-dihydroxy-11-keto-β-boswellic acid; 7β, 20β-dihydroxy-11-keto-β-boswellic acid; 7β, 30-dihydroxy-11-keto-β-boswellic acid; 3α, 7β-dihydroxy-11-oxours-12-ene-24, 30-dioic acid and 3α, 7β-dihydroxy-30-(2-hydroxypropanoyloxy)-11-oxours-12-en-24-oic acid by various spectroscopic methods. The biotransformation processes include hydroxylation, oxidation and esterification. Primary structure-activity relationships (SAR) of inhibitory effects on NO production in RAW 264.7 macrophage cells are discussed.


Computed tomography and sonographic findings of hepatic metastases from gastrointestinal stromal tumors after chemotherapy.
The purpose of this study was to evaluate the computed tomography (CT) and sonographic findings in patients with hepatic metastases from gastrointestinal stromal tumors (GISTs) after STI-571 treatment. Computed tomography and sonographic findings of 8 lesions in 6 patients with hepatic metastases from GISTs that were treated with STI-571 were retrospectively analyzed. The change in size, attenuation, and echogenicity of the hepatic metastases from GISTs after STI-571 treatment was evaluated. After treatment with STI-571, the hepatic metastases were decreased in size and the attenuation of the hepatic metastases was homogeneously hypodense on CT. Sonography revealed the hepatic metastases to be centrally cystic with a thin wall (n = 4) or predominantly solid (n = 4) after STI-571 treatment. On color Doppler sonography, no blood flow was identified within the solid portion of the mass. After treatment with STI-571, although the hepatic metastases from GISTs exhibit a cystic appearance on CT, they may appear as solid masses on sonography.


Gasotransmitters in non-alcoholic fatty liver disease: just the tip of the iceberg.
Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by fatty lesions and fat accumulation in hepatic parenchymal cells, which is in the absence of excessive alcohol consumption or definite liver damage factors. The exact pathogenesis of NAFLD is not fully understood, but it is now recognized that oxidative stress, insulin resistance, and inflammation are essential mechanisms involved in the development and treatment of NAFLD. NAFLD therapy aims to stop, delay or reverse disease progressions, as well as improve the quality of life and clinical outcomes of patients with NAFLD. Gasotransmitters are produced by enzymatic reactions, regulated through metabolic pathways in vivo, which can freely penetrate cell membranes with specific physiological functions and targets. Three gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide have been discovered. Gasotransmitters exhibit the effects of anti-inflammatory, anti-oxidant, vasodilatory, and cardioprotective agents. Gasotransmitters and their donors can be used as new gas-derived drugs and provide new approaches to the clinical treatment of NAFLD. Gasotransmitters can modulate inflammation, oxidative stress, and numerous signaling pathways to protect against NAFLD. In this paper, we mainly review the status of gasotransmitters research on NAFLD. It provides clinical applications for the future use of exogenous and endogenous gasotransmitters for the treatment of NAFLD.


Malunions of the finger metacarpals and phalanges.
Many malunions of the finger metacarpals are mild and do not require or justify operative intervention. Early recreation of the fracture or osteotomy is more likely to be rewarded with favorable results than late operation. Rotational malunions of the metacarpals or proximal phalanges may be treated by transverse extra-articular transverse or step-cut osteotomies at or proximal to the malunion site. Rotational malunions of the proximal phalanges as great as 200 in the index, middle, and ring fingers and 300 in the small finger may be managed by transverse extra-articular osteotomy at the adjoining metacarpal base. Angular and combined angular and rotational deformities of the metacarpal can be corrected by closing wedge osteotomy at the malunion site, with adjustment for malrotation when necessary. Angular and combined angular and rotational deformities of the proximal phalanx may be corrected by dorsal opening or lateral opening or closing wedge osteotomy, with derotation when needed. Articular malunions may be treated by osteotomy at the fracture site, a sliding osteotomy of the fracture and its proximal supporting cortex, or extra-articular osteotomy. Each approach for articular malunions has its potential risks and benefits. The true risks of articular malunion correction may not be fully known, because of the small number of cases in each presented series and the short follow-ups. Finger motion may be improved by correction of deformity alone, and may be further enhanced by tenolysis of adjacent adhesions. Capsulolysis may be helpful in instances of adjacent joint contracture. Despite improvement of finger motion in a majority of cases, some degree of remaining stiffness is common. Stiffness is almost always a residual of the original injury rather than a complication of corrective surgery, and serves to reinforce the fact that primary fracture reduction, stabilization, and rehabilitation are usually the best deterrents to malunion and consequent impairment. Much of the best available information has been gained from retrospective cohort or case study reports that may have inherent flaws in study design that limit their statistical validity and ability to detect trends. Flaws may include heterogeneity; investigator enthusiasm; and a lack of enrollment, prospective controlled randomization, blinding, confidence interval determinations, and follow-up. The statistical ability to determine trends in past reports may be compromised. Past reports provide important information and advances, but should be interpreted with some discretion. The pen may be mightier than the scalpel. In spite of encouraging reported results, phalangeal and articular osteotomies, in particular, remain daunting procedures for most hand surgeons. Prospective, controlled randomized studies maybe difficult to achieve in the clinical setting because of the time that would be necessary to secure adequate enrollments for statistical validity andthe occurrence of "dropouts" before completion of adequate follow-up. Meta-analysis is difficult because of variations in discriminators for patient selection and clinical outcomes. Although multicenter studies have their own inherent flaws, they may represent the best future option to add a higher level of study design and validity as compared with past studies. The incorporation of subjective patient outcome instruments into future studies might also provide valuable information. Investigators should review previous reports with a goal of improving study designs and scientific methodology, confirming or contradicting past results, or adding new information.


Clinical management of adolescents with autism.
Autism spectrum disorder is a spectrum of neurodevelopmental disorders that includes autistic disorder and pervasive developmental disorder-not otherwise specified. This article provides the reader with an overview of the major psychosocial issues related to adolescents with autism. This discussion is followed by an interjection of medications that may be useful in maximizing the functioning of adolescents with autism.


Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies.
The complement system plays a key role in the pathophysiology of kidney thrombotic microangiopathies (TMA), as illustrated by atypical hemolytic uremic syndrome. But complement abnormalities are not the only drivers of TMA lesions. Among other potential pathophysiological actors, we hypothesized that alteration of heparan sulfate (HS) in the endothelial glycocalyx could be important. To evaluate this, we analyzed clinical and histological features of kidney biopsies from a monocentric, retrospective cohort of 72 patients with TMA, particularly for HS integrity and markers of local complement activation. The role of heme (a major product of hemolysis) as an HS-degrading agent in vitro, and the impact of altering endothelial cell (ECs) HS on their ability to locally activate complement were studied. Compared with a positive control, glomerular HS staining was lower in 57 (79%) patients with TMA, moderately reduced in 20 (28%), and strongly reduced in 37 (51%) of these 57 cases. Strongly reduced HS density was significantly associated with both hemolysis at the time of biopsy and local complement activation (C3 and/or C5b-9 deposits). Using primary endothelial cells (HUVECs, Glomerular ECs), we observed decreased HS expression after short-term exposure to heme, and that artificial HS degradation by exposure to heparinase was associated with local complement activation. Further, prolonged exposure to heme modulated expression of several key genes of glycocalyx metabolism involved in coagulation regulation (C5-EPI, HS6ST1, HS3ST1). Thus, our study highlights the impact of hemolysis on the integrity of endothelial HS, both in patients and in endothelial cell models. Hence, acute alteration of HS may be a mechanism of heme-induced complement activation.


Systemic lupus erythematosus and discoid lupus erythematosus.
The management of a patient with SLE presents the OMS with a challenging array of decisions to make in regards to treatment sequencing. Careful reviews of the patient's medical history, the presentation of the illness, and the medication profile, and an open discourse with medical colleagues are necessary to ensure the safety of patients. By becoming comfortable with the medical treatment the patient is undergoing as well as having a firm understanding of where the patient is along the cascade of disease severity (see Fig. 7), appropriate decisions can be made in regards to the patient's outcome and prognosis. Proceeding into surgical treatment without following these guidelines could potentially result in catastrophic consequences for the patient.


HPIP promotes thyroid cancer cell growth, migration and EMT through activating PI3K/AKT signaling pathway.
Hematopoietic pre-B cell leukemia transcription factor (PBX)-interacting protein (HPIP), a co-repressor for the transcription factor PBX, is a nucleo-cytoplasmic shuttling protein. Increasing evidence suggests that HPIP is an oncogene which is frequently overexpressed in many human carcinomas. However, the role of HPIP in thyroid carcinoma is still unclear. Therefore, in this study, we investigated the role of HPIP in thyroid carcinoma, and explored the underling mechanism. We found that the expression of HPIP is upregulated in thyroid carcinoma cell lines. Knockdown of HPIP inhibits thyroid carcinoma cell proliferation, migration/invasion and epithelial-mesenchymal transition (EMT). HPIP knockdown also reduces thyroid tumor growth in nude mice. Furthermore, knockdown of HPIP significantly inhibits the expression of phosphorylated PI3K and AKT in thyroid carcinoma cells. Taken together, these results suggest that knockdown of HPIP inhibits the proliferation, migration and EMT by suppressing the PI3K/AKT pathway, and HPIP may be a potential therapeutic target for the treatment of thyroid carcinoma.


Association of eclampsia and hydatidiform mole: case report and review of the literature.
A patient with a hydatidiform mole complicated by eclampsia is presented. The findings from 57 other cases discovered in a review of the literature since 1866 are summarized to define the clinical characteristics of women experiencing eclampsia as a manifestation of their hydatidiform mole. Eclampsia complicating a molar pregnancy is generally preceded by typical preeclamptic symptomatology and uniformly by severely elevated blood pressure. Neurological or visual symptoms also commonly warn of impending eclampsia. Although the reported cases of eclampsia complicating molar pregnancies are rare, this risk argues for the liberal use of prophylactic antiseizure medication when caring for women with a hydatidiform mole and hypertension, neurological complaints, or other preeclamptic symptoms.


Pregnancies complicated by retained placenta: sex ratio and relation to pre-eclampsia.
Pre-eclampsia and placenta accreta have opposite histological features of placentation. This study set out to test the hypotheses that the sex ratios in these two pregnancy complications are opposite and that these conditions are mutually exclusive. A population-based database covering all deliveries in South Australia between 1986 and 1995 and the hospital-based obstetric database of the Adelaide Women's and Children's Hospital, covering 8549 births between 1993 and 1995, were used to ascertain the sex ratios in singleton pregnancies and the sex ratios in those pregnancies in which there was retained placenta, hypertension in pregnancy, or pre-eclampsia. The likelihood of independence of occurrence or mutual exclusivity of retained placenta and hypertension in pregnancy or pre-eclampsia were also examined. The male:female sex ratio in the South Australian population was 1.077. In pregnancies with hypertension in pregnancy it was 1.165 (P<0.001) and in pregnancies with retained placenta it was 0.883 (P<0.0001). There was a trend to an increased sex ratio in pre-eclamptic pregnancy (1.248 in primigravid and 1.092 in multigravid women) but there was insufficient power to detect significance (P=0.207 and 0.470, respectively). Neither hypertension in pregnancy nor pre-eclampsia were mutually exclusive of placenta accreta: hypertensive disorders of pregnancy and placenta accreta occurred independently of each other. Our findings suggest that sex-linked antigens are unlikely to influence maternofetal interactions consistently to give rise to one but not the other pregnancy complication.


The relationship between family support and the level of self care in type 2 diabetes patients.
The purpose of the study was to determine the relationship between family support and self-care in patients with type 2 diabetes in Middle Anatolia Region of Turkey. This descriptive relation-seeker-type study conducted with 284 patients who met inclusion criteria between February and May 2020 in the internal medicine and endocrinology clinics and polyclinics of a university hospital. Data were collected using, a demographic questionnaire, Hensarling's Diabetes Family Support Scale (HDFSS), and Diabetes Self-Care Scale (DSCS). Participants had a mean DSCS and HDFSS score of 83.20 ± 18.63 and 82.44 ± 28.04, respectively. There was a strong correlation between DSCS and HDFSS scores (r:.621) (p < 0.001). Participants' DSCS totals score was strongly correlated with their HDFSS "empathetic support" (p = 0.001, r = 0.625), "encouragement" (p = 0.001, r = 0.558), "facilitative support" (p = 0.001, r = 0.558), and "participative support" scores (p = 0.001, r = 0.555). Patients with more family support have higher levels of self-care. The results underline the significance of focusing on the relationship between self-care and family support in patients with type 2 diabetes.


[Hereditary angiœdema treatments: Recommendations from the French national center for angiœdema (Bordeaux consensus 2014)].
Treatment of hereditary angiœdema (HAE), associated or not with C1Inh deficiency, has dramatically changed these last five years. Four new therapeutic options are now available in France. The French Reference Centre for Angioedema has a consensus meeting to give recommendations about their use. The proposals were based on a CREAK survey and a comprehensive review of the literature done by 4 experts. These proposals were submitted to a vote at a national CREAK meeting (Bordeaux, March 2014). Fifty-one participants, 15 experts and one expert-patient have participated. The consensus concerned HAE patients with or without C1Inh deficiency. Were excluded children, patients with acquired AE and with drug induced AE. Proposals were done for 4 cases: acute attack treatment, short-term prophylaxis, long-term prophylaxis and pregnant women. The drugs cited were: C1Inh concentrate, icatibant, tranexamic acid, danazol and chlormadinone acetate. Consensual proposals were obtained during this meeting. They will be now widely diffused.


Characteristics of two cancer cell lines derived from metastatic foci in liver and peritoneum of a patient with colon cancer.
Two cancer cell lines were established in vitro from a single patient with colon cancer; AKT-CC-K-LM cells from liver metastatic nodules and AKT-CC-K-PC cells from peritoneal dissemination nodules. The two cell lines were similar in doubling time, number of chromosomes, and chromosomal abnormalities. However, they differed in morphology in vitro, in the expression level of cell surface adhesion molecules (carcinoembryonic antigen; CEA, E-cadherin, sialyl Le(a), sialyl Le(x), and CD44v6), and in their metastatic properties. AKT-CC-K-LM cells grew in vitro as adherent clusters and AKT-CC-K-PC cells as adherent single cells. The expression levels of CEA, E-cadherin, sialyl Le(a), and sialyl Le(x) was significantly higher in AKT-CC-K-LM cells. The expression of CD44v6 was significantly higher in AKT-CC-K-PC cells. After the injection of AKT-CC-K-LM cells to the spleen or peritoneal cavity of severe combined immune deficiency mice, metastatic nodules were observed only in the liver. In contrast, the injection of AKT-CC-K-PC cells to the spleen or peritoneal cavity yielded metastatic nodules only in the peritoneal cavity. These cell lines may contribute to elucidating the relationship between cell surface adhesion molecules and the metastatic properties of cancer cells.


HBO1 catalyzes lysine benzoylation in mammalian cells.
Lysine benzoylation (Kbz) is a newly discovered protein post-translational modification (PTM). This PTM can be stimulated by benzoate and contributes to gene expression. However, its regulatory enzymes and substrate proteins remain largely unknown, hindering further functional studies. Here we identified and validated the lysine acetyltransferase (KAT) HBO1 as a "writer" of Kbz in mammalian cells. In addition, we report the benzoylome in mammalian cells, identifying 1747 Kbz sites; among them at least 77 are the HBO1-targeted Kbz substrates. Bioinformatics analysis showed that HBO1-targeted Kbz sites were involved in multiple processes, including chromatin remodeling, transcription regulation, immune regulation, and tumor growth. Our results thus identify the regulatory elements of the Kbz pathway and reveal the non-canonical enzymatic activity and functions of HBO1 in cellular physiology.


Correction to: Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment.
The author name G. A. Chastikina should read G. A. Chastikin.


Shock-absorbing effect of flooring-adopted mechanical metamaterial technology and its influence on the gait and balance of older adults.
To elucidate the performance of a shock-absorbing floor material with a mechanical metamaterial (MM-flooring) structure and its effect on the gait and balance of older adults. The drop-weight impact was applied to evaluate the shock-absorbing performance. The falling weight was adjusted equivalent to the energy exerted on the femur of an older woman when she falls, which was evaluated on the MM-flooring and six other flooring materials.Nineteen healthy people over the age of 65 years participated in the gait and balance evaluations. The timed up and go and two-step tests were adopted as gait performance tests, and the sway-during-quiet-balance test with force plates and the functional reach test (FRT) were adopted as balance tests. All the participants underwent these tests on the MM-flooring, shock-absorbing mat and rigid flooring. The shock-absorbing performance test revealed that MM-flooring has sufficient shock-absorbing performance, and suggesting that it may reduce the probability of fractures in the older people when they fall. The results of the gait performance test showed that the participants demonstrated the same gait performance on the MM-flooring and the rigid floor. In the quiet standing test, MM-flooring did not affect the balance function of the participants to the same extent as the rigid floor, compared with the shock-absorbing mat. In the FRT, no significant differences were found for any of the flooring conditions. MM-flooring has the potential to prevent fractures attributed to falls and does not affect the gait or balance of older adults.


An anti-prostate cancer benzofuran-conjugated iridium(III) complex as a dual inhibitor of STAT3 and NF-κB.
Four benzofuran-conjugated iridium(III) or rhodium (III)-based metal complexes are synthesized to screen as an inhibitor of STAT3 activity in prostate cancer cells. All complexes show the high stability and solubility in the biological system. In this study, an iridium(III) complex engages STAT3 and NF-κB to inhibit their translocation and transcriptional activities. Moreover, complex 1 shows more potential antiproliferative activity against DU145 cells and suppresses tumor growth in a prostate cancer xenograft mouse without observable adverse effects. Complex 1 may provide the basis for developing new therapeutic strategy in vivo and in vitro for the treatment of advanced prostate cancer.


Effectiveness of exercise and pramipexole in the treatment of restless leg syndrome: Implications on the dopaminergic system and PTPRD.
Dopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). Animals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX). PPX treatment was performed daily (0.125 mg/kg), while exercise was conducted over 5 sessions per week, both for 4 weeks. EX + PPX increased the protein levels of PTPRD, reduced the protein levels of the enzyme tyrosine hydroxylase (TH) and improved sleep parameters in both cycles; on the other hand, the use of PPX reduced mRNA and protein levels of PTPRD and TH but improved the sleep pattern in the light cycle. However, in the dark cycle, pramipexole caused the worsening of symptoms. We suggest that the improvement in sleep pattern by EX + PPX may be associated with the increased protein levels of PTPRD and that EX + PPX can reverse the negative effects of PPX.


[Effect of ionization of system components on the interaction of polyuridylic acid with adenosine. Deprotonation of the polynucleotide].
The interdependence of complex formation and poly(U) deprotonation in the poly(U)-adenosine system has been studied by UV spectroscopy, titration and equilibrium dialysis techniques. Evidence is presented on the formation of an intermediate, probably double helical, structure in the course of A-2 poly(U) dissociation at alkaline pH.


The pathogenesis of the rheumatoid swan neck deformity.
Disappointment with the late results of intrinsic release for the rheumatoid "intrinsic-plus" hand has led to a re-appraisal of the role of intrinsic muscle contracture in the pathogenesis of the rheumatoid swan neck deformity. In cadaveric fingers, a properly placed suture typing the lateral band to the middle slip insertion causes a swan neck deformity. It is suggested that the usual "intrinsic-plus" hand and the fixed swan neck deformity of rheumatoid arthritis is caused by adhesions between the extensor tendons on the dorsum of the proximal interphalangeal joint, rather than by intrinsic muscle contracture and/or metacarpo-phalangeal dislocation.


The response of the antioxidant defense system in rat hepatocytes challenged with oxysterols is modified by Covi-ox.
Suspension cultures of isolated rat hepatocytes were used to investigate whether 7-ketocholesterol and cholestane-3beta,5alpha,6beta-triol exert oxidative stress in cells as manifested by increased lipid peroxidation and the induction of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase. The oxysterols were found to increase the levels of both superoxide dismutase and catalase and to have variable effects on glutathione peroxidase activity. Increased lipid peroxidation was not observed, indicating that the endogenous antioxidant defense system was capable of protecting against any oxidative stress that might otherwise by exerted by 7-ketocholesterol or cholestane-3beta,5alpha,6beta-triol. Covi-ox, a natural tocopherol blend reduced the effects of both oxysterols on the antioxidant enzymes. A concurrent reduction in the production of thiobarbituric acid-reactive substances in Covi-ox-treated cells is indirect evidence that reactive oxygen species were produced by oxysterols in hepatocyte suspension cultures.


[Parasitic influences on undifferentiated tissue (author's transl)].
The imaginal discs of chironomid larvae infected with mermithid nematodes provided a useful model for the study of parasitic effects upon undifferentiated tissue. Specific aberrations concerning mitotic rate, cell death, organogenesis, cell pattern differentiation and cell differentiation are described and discussed.


Flow injection photometric determination of NaCl, KCl and glucose in injectable drugs exploiting Schlieren signals.
A flow injection photometric system that exploits Schlieren signals for analytical measurement is described. The system was designed to be used as a new strategy for determining the contents of sodium chloride, potassium chloride and glucose, each respectively in injectable drugs. The proposed methodology was based on the difference between the refractive indices of the sample zone and of the carrier stream. With this perspective, a lab-made photometer based on LED-phototransistor technology was employed as a detection system to investigate the different analytical profiles related to the Schlieren effect in low flow rate conditions. The parameters of the flow system, such as flow-rate, optical path length, and sampling loop, were adjusted in order to obtain suitable Schlieren profiles for the measurements. Data evaluation was performed with the application of partial least squares regression (PLS-1). The obtained results demonstrated the predictive ability of the constructed PLS models, and the predicted concentration values were in agreement with the reference values, with a 95% confidence level.


[Origin and evolution of the genetic code].
We propose a quantitative model which suggests that the present genetic code appeared under the influence of mutations, while optimizing its own resistance against their effects. Its evolution was realized by successive steps in which the number of translated codons grew, whereas the number of terminators decreased. The main constraint of this model is selection against nonsense mutations: the competition among many primitive codes gives advantage to those which resist best to the occurrence of nonsense mutations. The structures of the selected systems converge towards that of the present genetic code. This one appears then as built so as to resist to errors, information noise, mutations.


Basophilic leukaemia in a dog.
Leukaemia in an 11-year-old bitch was characterized by the presence in the peripheral blood and bone marrow of cells with lobulated nuclei and numerous metachromatic cytoplasmic granules. The results of cytochemical stains for peroxidase and naphthol AS-D chloracetate esterase activity were negative. Ultrastructurally, the cytoplasmic granules were finely granular with no membranous coils or crystalline lattice structures. Based on these findings, the neoplastic cells were classified as basophils.


Fuzzy evaluation on the integrated benefit of regulated deficit irrigation for pear-jujube tree based on information entropy.
Based on the experimental data of regulated deficit irrigation at different growth stages on field pear-jujube tree (Zizyphus jujube Mill.) during 2005-2007 in Northwest China, the regulated deficit irrigation integrated benefits (RDIIB) with different water deficit treatments at different growth stages were evaluated and classified using a model. The results in 2005-2006 showed that the RDIIB under single-stage water deficit at fruit maturity stage were better than the other treatments, and the best RDIIB were gained under moderate (IVSD) or severe deficit (IVMD) at fruit maturity stage. The results in 2006-2007 also indicated that the four double-stage water deficit schemes have the better RDIIB, and the best scheme was severe water deficit at bud burst to leafing stage plus moderate water deficit at fruit maturity stage. The RDIIB evaluation model based on information entropy method provided the reliable technical guidance for the optimal RDI scheme of pear-jujube tree.


Applying the Addictions Neuroclinical Assessment to derive neurofunctional domains in individuals who use methamphetamine.
The Addictions Neuroclinical Assessment (ANA) was proposed as a neuroscience-informed clinical framework to understand heterogeneity in addiction encompassing dysfunction in three domains: incentive salience, negative emotionality, and executive functions. The ANA has been validated in the alcohol field but has not been extended to other substances. Thus, the objective of the current study was to replicate and extend the ANA framework to methamphetamine use disorder. Non-treatment seeking individuals (N = 185) who reported regular methamphetamine use completed a deep phenotyping battery comprising self-report and behavioral measures that assessed methamphetamine craving and emotional withdrawal symptoms, mood and anxiety symptomatology, risk-taking behaviors, working memory, attention, and impulsivity. Factor analytic techniques were used in an iterative manner to derive latent factors that explained biobehavioral variation in the sample. The relationship between factor scores and demographic and clinical indicators of methamphetamine use were examined to assess the construct validity of the latent factors. Deep phenotyping combined with factor analytic techniques implicated three intercorrelated neurofunctional domains that map on to the proposed ANA domains: incentive salience, negative emotionality, and executive function. Each of the domains were associated with demographic and clinical indicators of methamphetamine use providing initial support for their construct validity. The ANA framework holds promise for explaining heterogeneity in addiction by identifying neuroscience-informed phenotypes. Knowledge from the ANA framework may be applied to advance precision medicine and inform medications development for a host of substance use disorders, particularly those with no approved pharmacotherapy such as methamphetamine.


Application of pulse mixing method in software coincidence counting.
In recent years the software coincidence counting system, designed for absolute activity measurement, has been developed in the Czech Metrology Institute. In this system a true coincidence count rate is calculated from the records of time and amplitude data of individual pulses and may be determined by two different methods. The first one uses a coincidence resolving time, in a manner similar to a classical coincidence measurement. The second method applies the pulse mixing method formulae, so that it does not use the resolving time and the correction for accidental coincidences. Both methods have been tested on the same data from a 4pibeta (PC)-gamma coincidence measurement of 60Co sources. The difference between the results obtained from both calculation methods applied on the data from the same measurement did not exceed 0.015%. The details of both methods and the results of their comparison are presented.


Severe thiamine deficiency in sheep with acute ruminal lactic acidosis.
Thiamine status of ruminants is adversely affected in acidic rumen conditions. However, there have been limited published case study data related to thiamine deficiency of ruminants with acute ruminal lactic acidosis (ARLA). Thiamine deficiency would occur in sheep with ARLA. Thirteen Ak-Karaman (white Karaman) sheep with ARLA, aged 1 year (ARLA group) and 10 healthy Ak-Karaman sheep, aged 1 year (control group) were used. After clinical examination, rumen fluid samples of all sheep were obtained with a stomach tube and examined immediately. Blood samples were taken from a jugular vein of the sheep. Erythrocytic transketolase enzyme activity and hence thiamine pyrophosphate (TPP) effect were determined according to Clausen's method. History revealed that all sheep in the ARLA group had accidentally consumed excessive amounts of cracked barley. During clinical examination of the ARLA group, disturbed general condition, engorged scleral vessels, moderate to severe dehydration, and ruminal atony were recorded in the sheep. The results of the ruminal fluid analyses of the ARLA group demonstrated characteristics of ARLA. The results of clinical and ruminal fluid examination of control group were normal. The mean TPP effect (%) in the ARLA group (109 +/- 28) was significantly higher than in the control group (22.2 +/- 3.7) (P < .001). The present study revealed that severe thiamine deficiency occurred in sheep with ARLA. This result indicates that thiamine administration to sheep suffering from acute ruminal acidosis caused by overconsumption of readily fermentable carbohydrates could be beneficial in alleviating thiamine deficiency caused by ruminal acidosis.


Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet.
Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD.


Limited granulomatosis with polyangiitis in children with idiopathic orbital inflammation: a case series and literature review.
Idiopathic orbital inflammation (IOI) is a diagnosis of exclusion, but the exclusion of other inflammatory diseases of the orbit is broad and relies on clinician experience, response to corticosteroid, or biopsy. This study aimed to investigate the presence of granulomatosis with polyangiitis (GPA) in patients initially diagnosed as IOI and describe its clinicopathological features, ANCA status, treatment, and outcome. We performed a retrospective case series study of children diagnosed with limited GPA (L-GPA) in patients with IOI. A systematic review of the literature was performed in children with GPA and orbital mass. Eleven of 13 (85%) patients with IOI had L-GPA. Two additional patients with orbital mass and L-GPA were included in this analysis. The median age was 10 years, and 75% were female. Twelve cases were ANCA positive and 77% were MPO-pANCA positive. Most patients had a poor response to treatment and had a high relapse rate. Based on literature review, 28 cases were found. Most (78.6%) were female with a median age of 9 years. Three patients were misdiagnosed as IOI. Patients with L-GPA more frequently had MPO-pANCA positivity (35%) than children with systemic GPA (18%) and were less often PR3-cANCA positive than patients with systemic GPA (18% vs. 46%). L-GPA accounts for a high prevalence of children diagnosed as IOI. The high prevalence of MPO-pANCA observed in our study may be related to L-GPA rather than with the orbital mass. Long-term follow-up, orbital biopsy, and serial ANCA testing are necessary to exclude GPA in patients with IOI.


Cytoskeletal characteristics of myofibroblasts in benign neoplastic and reactive fibroblastic lesions.
The characteristics of the cytoskeleton of myofibroblasts were examined immunohistochemically in 10 extra-abdominal desmoid tumours, 3 palmar and 2 plantar fibromatoses and 5 nodular fasciitis; in the cultured cells of one desmoid tumour, and also ultrastructurally in 3 desmoid tumours. Polyclonal anti-desmin antibody reacted with the cells in 7 extra-abdominal desmoid tumours, 1 palmar fibromatosis, 1 plantar fibromatosis and 3 nodular fasciitis. Monoclonal antidesmin antibody reacted with cells in only 2 desmoid tumours. Desmin-positive spindle cells were scattered throughout these lesions. There were no marked ultrastructural differences between desmin-positive and desmin-negative desmoids. All specimens except one specimen of nodular fasciitis showed immunoreactivity for alpha-smooth muscle actin and vimentin. Muscle actin-positive cells were observed in all specimens. Cultured cells gave positive reactions with polyclonal desmin antibody as well as to vimentin antibodies and two preparations of actin antibodies, whereas the original tumour did not react with desmin antibody. The present studies suggested that the cytoskeleton of some myofibroblasts in both neoplastic and reactive lesions resembles that of smooth muscle cells.


Dental Practices and Awareness toward the Impact of Periodontal Disease on Systemic Health among Medical Doctors in Jazan, Saudi Arabia.
To evaluate knowledge and awareness of medical doctors regarding the impact of periodontal disease on a set of systemic diseases. A questionnaire-based cross-sectional study recruiting medical doctors in Jazan region. One hundred participants from four governmental hospitals in Jazan city responded to multiple-choice-question-type questionnaire. The obtained data were analyzed using SPSS version 20. For Chi-square test, p-value ≤0.05 was considered significant. In our study, participants had a positive attitude toward their self-oral hygiene practices. Regarding knowledge, only 5% got their information from medical curricula. Most of the participants (90%) agreed that oral disease impacts general health; nevertheless, their awareness of the impact of periodontal disease on specific body systems was poor. There was a significant correlation between positive oral hygiene practices and gender, age, and experience. Our study showed limited knowledge of medical doctors about the association between periodontal diseases and general health. It also reflected poor medical curricula in this regard. It is strongly recommended to include oral health-relevant subjects in medical curricula and continuous medical education programs and to stress on the joint subjects that require multidisciplinary care. Improving the awareness of medical health providers about the association between periodontal diseases and general health improves the well-being and patient management.


Injuries due to deliberate violence in areas of Denmark. III. Lesions. The Copenhagen Study Group.
As part of a transcultural investigation of violent behavior in Denmark and South America, the lesions from accidents involving deliberate violence registered in three Danish emergency wards during a 1-year period were studied. A quantity of 2211 lesions were diagnosed in 1316 patients (953 male and 363 female patients). Sixty-five percent of the lesions were in the head/neck region, 13% in truncus, 18% in the upper extremities and 5% in the lower extremities. The most frequent diagnosis was an open wound in the head/neck region. Adding contusions and fractures in the same region this amounted to more than half of the total number of lesions. In the upper extremities 62% of the lesions were contusions or open wounds. Serious lesions of internal arteries were few, however always caused by sharp instruments (knives). Serious lesions due to firearms were not recorded/reported. Strangulation had been used against 1.1% of the victims, the male/female ratio being 1:6. The main part of the lesions were of minor severity when assessed on the basis of the scores in the Abbreviated Injury Scale (AIS). The lesions were, however, more serious compared to other recent studies, and it appeared that the female victims had fewer but more serious lesions than the male victims. The need for treatment and hospitalization was in the range of other recent studies.


Experience of the Hungarian Preconception Service between 1984 and 2010.
The objective of this historical account is to summarize the concept, objectives, methods, results and general experience of the Hungarian Preconception Service, Budapest, based on 27 years (1984-2010) and 25,313 women and couples. The service includes counseling and care (examinations and medical interventions) based on three steps: (1) preconception screening for reproductive risk factors ("reproductive health check-up"), (2) a 3-month preparation for conception, because conception is when some major developmental events, such as the sex of the conceptus and the foundation of health and many diseases, are determined, and (3) achievement of optimal conception and better protection of the embryo in early pregnancy. With normal prenatal care, pregnant women visit clinics between the 7th and 12th gestational weeks, but the embryo has passed through his/her most vulnerable period before the 10th week, and thus prenatal care is too late to reduce the risk of congenital abnormalities. The new primary health care infrastructure for preconception care is performed by qualified and trained nurses and midwifes. Couples at risk are selected and are referred to specialists who can reject or confirm the supposed risks and treat the couples if necessary as part of their secondary health care. The most important results of the Hungarian preconception service were (i) a significant reduction in the rate of preterm births (5.0% vs. 9.2%) which has been linked mainly to preconception screening of sexually transmitted infections of female participants followed by appropriate treatment, (ii) a very significant reduction of congenital abnormalities (2.9% vs. 4.0%), particularly neural-tube defects and cardiovascular malformations, due to periconception multivitamin supplementation, (iii) reduction of smoking among female participants, (iv) involvement of male partners in the family planning health system, (v) much improved identification of couples at high risk and greater access to the secondary care of specialists. In conclusion, the Hungarian experience demonstrates the feasibility and usefulness of preconception care in the prevention of adverse birth outcomes including congenital abnormalities and preterm births.


Acute changes in osmolality and renin and respiratory control of arterial PCO2 and [H+].
To investigate whether osmoreceptor mechanisms or the renin-angiotensin system might be involved in respiratory regulation of H+ homeostasis, plasma osmolality was acutely lowered by approximately 10 mOsm in 7 awake mongrel dogs by a gastric water load (20 ml.kg-1 distilled, deionized water). Plasma renin activity (PRA) was measured as an indicator of angiotensin II levels. During these studies PaCO2 and [H+]a reflected the spontaneous level of ventilation (VE); higher levels of VE were correlated with lower PaCO2 and [H+]a, indicating a nonchemical drive to breathe. Stimulation of ventilation to lower PaCO2 following the water load was positively correlated with increase in PRA and decrease in plasma osmolality, but not with change in osmolality alone. An increased VE, a decreased ventilatory response curve (VRC) threshold for PaCO2, and a lower PaCO2 occurred with increase in PRA. Conversely, a lower or acutely decreased PRA, due to administration of arginine vasopressin, was correlated with a lower VE, an increase in the VRC threshold for PaCO2, and a higher PaCO2. Ventilatory control of PaCO2 during acute lowering of osmolality may be related to a central inter-action between osmolality and the renin-angiotensin system.


Effects of Macroplastique Implantation System for stress urinary incontinence and urethral hypermobility in women.
A study was carried out to evaluate efficacy of Macroplastique(R) (MPQ) Implantation System (MIS) in women with urodynamic stress urinary incontinence (SUI) and urethral hypermobility after an unsuccessful conservative treatment. This is a prospective randomized controlled trial in women without previous incontinence surgery. Twenty-four women received MPQ. Twenty-one controls underwent a pelvic floor muscle exercises home program. Follow-up was at 3 months and the MPQ group also at 12 months. At 3 months, pad usage decreased significantly more in the MPQ group than in the control group (p = 0.015). According to physician and patient self-assessment, respectively, 71% and 63% women in the MPQ group were considered cured or markedly improved. This was significantly higher compared to controls. There was a significant higher increase of Incontinence Quality-of-Life questionnaire score in the MPQ group compared to controls (p = 0.017). Improvements in MPQ group at 3 months are sustained to 12 months. Adverse events were mild and transient. MIS is an acceptable option for women with SUI and urethral hypermobility.


Interplay between invertebrate C3a with vertebrate macrophages: functional characterization of immune activities of amphioxus C3a.
Our current knowledge of the structure and function of C3a comes from the study of vertebrate C3a anaphylatoxins, virtually nothing is known about the structure and function of C3a molecules in invertebrates. Here we demonstrated that C3a from the invertebrate chordate Branchiostoma japonicum, BjC3a, was similar to vertebrate C3a possessing potential antibacterial activity, as revealed by sequence analysis and computational modeling. The antibacterial activity of BjC3a was definitely confirmed by both antibacterial assay and TEM observation showing that recombinant BjC3a was directly bactericidal. Additionally, recombinant BjC3a, like vertebrate C3a, was capable of inducing sea bass macrophage migration and enhancing macrophage phagocytosis and respiratory burst response. Moreover, recombinant BjC3a-desArg (generated by removal of the C-terminal arginine), like mammalian C3a-desArg, retained the immunological activities of BjC3a such as antibacterial and respiratory burst-stimulating activities, indicating that the immunological functions of C3a-desArg were conserved throughout chordate evolution. Altogether, our findings show that invertebrate (amphioxus) BjC3a is able to interact with vertebrate (sea bass) macrophages and mediate immune activities, suggesting the emergence of the inflammatory pathway of the complement system similar to that of vertebrates in the basal chordate amphioxus.


Cytotoxic Constituents and Mechanism from Peganum harmala.
Peganum harmala L. is a traditional Chinese and Uygur medicine used to treat cancer. Bioactivity-guided fractionation was applied to determine the cytotoxic constituents from P. harmala. A novel triterpenoid and a phenolic glycoside were isolated and identified, as well as seven known compounds. The novel metabolites were elucidated to be 3α-acetoxy-27-hydroxyolean-12-en-28-oic acid methyl ester (1, OA) and N-acetyl-9-syringinoside (9). Some compounds exhibited potent cytotoxicity against human tumor cells. Among them, OA showed the highest cytotoxicity against human lung cancer cells A549 with an IC50 value of 8.03 ± 0.81 μm. OA had a potent anti-NSCLC cell activity by interfering with the epidermal growth factor receptor (EGFR) activation and its downstream signaling, and could exert an antiproliferative effect by inactivation of EGFR-driven antiapoptotic pathway followed by the release of mitochondrial cytochrome c, which might prove to be a promising leading compound for the development of an anti-lung cancer drug.


The incidence of major complications from Mohs micrographic surgery performed in office-based and hospital-based settings.
There has been significant interest in the safety of office-based surgery. Our purpose was to compare the safety of Mohs micrographic surgery and related surgical repairs performed in office- and hospital-based settings. The study included 3937 consecutive patients undergoing Mohs surgery. Surgery was performed at either an outpatient office or a hospital-based setting. Mohs surgery was performed on 1540 patients in the hospital and 2397 patients underwent surgery in the office. The mean patient age was 66 years, and 61% were men. Ninety-three percent of lesions were basal cell or squamous cell carcinomas, and 86% were located on the head and neck. The average tumor measured 1.1 x 1.0 cm, required 1.7 stages of Mohs surgery, and resulted in a defect measuring 2.4 x 1.8 cm. Linear closures, flaps, grafts, and second-intention healing were utilized in 69%, 14%, 6%, and 11% of defects, respectively. There were no differences in patient or tumor characteristics or the types of closures used at the two operating facilities. The only serious surgical complication was gastrointestinal hemorrhage due to naproxen prescribed postoperatively for auricular chondritis in one patient. Mohs micrographic surgery and repair of associated defects can be safely performed in either an office- or hospital-based setting.


Toxicology and pharmacology of sodium ricinoleate.
Ricinoleic acid constitutes approximately 90% of the fatty acid content of castor oil. Castor oil is known for its purgative effects and can be used to induce labor. Both castor oil and ricinoleic acid are approved for use in food. The mechanistic basis for purgative actions likely includes the membrane-disruptive effects of detergent-like molecules, such as sodium ricinoleate (a 'soap'). These effects have been shown to be dose-related and to exhibit a threshold below which no laxative response was evident, in both animals and in humans. Castor oil was not toxic in subchronic feeding studies in rodents at doses ranging up to 10-20% of the diet. Sodium ricinoleate, as a surfactant, demonstrates predictable skin and mucus membrane irritant effects, and may induce a Type IV dermal sensitization response in those previously sensitized to it. However, food-grade castor oil and sodium ricinoleate are prepared in such a manner as to be free of the castor bean constituents that have been proven to be the source of reported Type I immediate hypersensitivity responses. Feeding studies with castor oil in rodents provide a basis for a no observable adverse effect level (NOAEL) estimate of 7,500 mg/kg/day and 5,000 mg/kg/day in mice and rats, respectively (). Applying an uncertainty factor of 100 to the lesser of these NOAELs, one can thus estimate an acceptable daily intake (ADI) in man to be 50 mg/kg, or 3,000 mg of castor oil per day in an average 60 kg person. As ricinoleic acid constitutes approximately 90% of castor oil, applying this calculation to the 3,000 mg/day estimated ADI in humans for castor oil (given the rapid hydrolysis of castor oil glyceride in the gastrointestinal tract), the acceptable daily intake of ricinoleic acid may be as high as 2,400 mg/person.


Effects of ruthenium ions on the sensory terminal discharges of the frog muscle spindle.
The presence of a mixed Na+-Ca2+ spike along the sensory terminal of the frog muscle spindle was verified. When the terminal was perfused with Ringer's solution containing 0.1-0.5 mM ruthenium red (RuR), the amplitude and duration of the spike were increased, occurring as a prolonged or a long-lasting depolarization of up to 20-30 s duration following individual afferent spikes evoked spontaneously or antidromically by electrical stimulation. In an isotonic TEA solution, the amplitude and duration of the afferent spikes were increased; however, no prolonged depolarization occurred. Adding 0.2 mM RuR to the TEA solution produced the prolonged and long-lasting depolarization. All responses disappeared in the presence of 3 microM TTX or Na+-free Ringer's solution. An impedance decrease along the terminal was observed during the prolonged or long-lasting depolarization. The prolonged depolarization was blocked by the addition of Ca2+-blockers; the afferent spikes remained. In preparations preincubated with 0.1 mM RuR, increasing CaCl2 in Ringer's solution from 0.2 mM, resulted in shortening of the duration of individual spikes with prolonged depolarization and in increase in the maximum rate of rise (MRR) of the spikes. Preincubation with higher concentrations of RuR produced higher sensitivities in the modifications of the duration and MRR to the change in [Ca2+]O. The responses were retained by adding RuR or RuCl3 to Ca2+-free Ringer's solution containing 0.1-5 mM EGTA, although all responses disappeared in Ca2+-free EGTA Ringer's solution. It is concluded that the RuR-induced prolonged response is produced by an influx of Na+.


Collaborative learning of graph generation, clustering and classification for brain networks diagnosis.
Accurate diagnosis of autism spectrum disorder (ASD) plays a key role in improving the condition and quality of life for patients. In this study, we mainly focus on ASD diagnosis with functional brain networks (FBNs). The major challenge for brain networks modeling is the high dimensional connectivity in brain networks and limited number of subjects, which hinders the classification capability of graph convolutional networks (GCNs). To alleviate the influence of the limited data and high dimensional connectivity, we introduce a unified three-stage graph learning framework for brain network classification, involving multi-graph clustering, graph generation and graph classification. The framework combining Graph Generation, Clustering and Classification Networks (GraphCGC-Net) enhances the critical connections by multi-graph clustering (MGC) with a supervision scheme, and generates realistic brain networks by simultaneously preserving the global consistent distribution and local topology properties. To demonstrate the effectiveness of our approach, we evaluate the performance of the proposed method on the Autism Brain Imaging Data Exchange (ABIDE) dataset and conduct extensive experiments on the ASD classification problem. Our proposed method achieves an average accuracy of 70.45% and an AUC of 72.76% on ABIDE. Compared with the traditional GCN model, the proposed GraphCGC-Net obtains 9.3%, and 10.64% improvement in terms of accuracy and AUC metrics, respectively. The comprehensive experiments demonstrate that our GraphCGC-Net is effective for graph classification in brain disorders diagnosis. Moreover, we find that MGC can generate biologically meaningful subnetworks, which is highly consistent with the previous neuroimaging-derived biomarker evidence of ASD. More importantly, the promising results suggest that applying generative adversarial networks (GANs) in brain networks to improve the classification performance is worth further investigation.


Reply to Comment on 'Linear energy transfer incorporated intensity modulated proton therapy optimization'.
In this reply we present additional description of our linear model for LET optimization in response to the comments by Dr Gorissen. We clarify that this model cannot guarantee global optimal solutions to the sum-of-fractions problem. Based on our data, it could be used to optimize LET efficiently while dose constraints are maintained.


Cross-linking of human T cell receptor proteins: association between the T cell idiotype beta subunit and the T3 glycoprotein heavy subunit.
Bifunctional cross-linking reagents DSP, DSS, and BSOCOES were used to cross-link 125I-surface-labeled viable T lymphocytes. The cross-linked cells were solubilized in Nonidet-P40, immunoprecipitated with anti-Ti (monoclonal antibody T40/25) or anti-T3 (monoclonal antibodies UCHT-1 or OKT3), and analyzed by SDS-PAGE. With all three cross-linkers, the intact cross-linked products obtained with monoclonal antibody T40/25 from HPB-ALL cells were 20-30 kd heavier than the Ti dimer (Mr 80,000). When the DSP cross-linked product was isolated using either anti-Ti or anti-T3 monoclonal antibodies and then cleaved, bands having molecular weights identical with both the Ti and T3 subunits were obtained. The two-dimensional SDS-PAGE analysis (nonreducing followed by reducing conditions) of the DSS and BSOCOES cross-linked products revealed the specifically cross-linked bands to have Mr 40,000 and Mr 28,000. These data indicate that the Ti molecule and the T3 molecule are spatially associated on the cell surface and suggest the predominant association is between the Ti beta subunit (Mr 40,000) and the T3 heavy subunit (Mr 28,000).


Regulation of activated protein C by a new protein. A possible function for bovine protein S.
The rate of inactivation of activated Factor V (Factor Va) by activated protein C can be enhanced by the addition of plasma. Plasma alone, however, had no effect upon Factor Va activity. This observation indicated that plasma may contain a cofactor for activated protein C. The cofactor activity was removed from plasma by barium citrate absorption and was eluted from the barium pellet. The cofactor activity eluted slightly ahead of prothrombin when chromatographed on quaternary aminoethyl (QAE)-Sephadex. The activity appeared to co-chromatograph with a protein that has been designated protein S. Purified cofactor-protein S had no effect upon the activity of purified bovine Factor Va either in the presence or in the absence of phospholipid. Purified cofactor-protein S caused a large enhancement in the rate of inactivation of Factor Va by activated protein C in the presence of phospholipid. These results indicate that protein S may be a cofactor for activated protein C.


Global determinants of insect mitochondrial genetic diversity.
Understanding global patterns of genetic diversity is essential for describing, monitoring, and preserving life on Earth. To date, efforts to map macrogenetic patterns have been restricted to vertebrates, which comprise only a small fraction of Earth's biodiversity. Here, we construct a global map of predicted insect mitochondrial genetic diversity from cytochrome c oxidase subunit 1 sequences, derived from open data. We calculate the mitochondrial genetic diversity mean and genetic diversity evenness of insect assemblages across the globe, identify their environmental correlates, and make predictions of mitochondrial genetic diversity levels in unsampled areas based on environmental data. Using a large single-locus genetic dataset of over 2 million globally distributed and georeferenced mtDNA sequences, we find that mitochondrial genetic diversity evenness follows a quadratic latitudinal gradient peaking in the subtropics. Both mitochondrial genetic diversity mean and evenness positively correlate with seasonally hot temperatures, as well as climate stability since the last glacial maximum. Our models explain 27.9% and 24.0% of the observed variation in mitochondrial genetic diversity mean and evenness in insects, respectively, making an important step towards understanding global biodiversity patterns in the most diverse animal taxon.


Learning ability in adult female rats perinatally exposed to methadone.
Cognitive functioning of adult female rats that were maternally exposed to methadone (5 mg/kg daily) during gestation and/or lactation was studied by assessing performance on a food-motivated light-dark discrimination learning test and on active and passive shock-avoidance tests. Methadone-exposed rats exhibited difficulties on the light-dark discrimination learning and the active avoidance tests, and behavioral deficits appeared to be related to the timing and duration of drug treatment. On the light-dark discrimination test only 33% of the rats in the gestation group and 25% of the animals in the lactation group met criterion in comparison to 87% of the control rats. Thirty-three percent of the animals in either the gestation or gestation-lactation groups met criterion on the active avoidance test in contrast to 87% of the controls. These data suggest that perinatal exposure to methadone impairs cognitive abilities in the adult female rat.


The traditional food of migrants: Meat, water, and other challenges for dietary advice. An ethnography in Guanajuato, Mexico.
The term "traditional diet" is used variously in public health and nutrition literature to refer to a substantial variety of foodways. Yet it is difficult to draw generalities about dietary tradition for specific ethnic groups. Given the strong association between migration and dietary change, it is particularly important that dietary advice for migrants be both accurate and specific. In this article, I examine the cultural construct of "traditional foods" through mixed method research on diet and foodways among rural farmers in Guanajuato, MX and migrants from this community to other Mexican and U.S. destinations. Findings reveal first, that quantitatively salient terms may contain important variation, and second, that some "traditional" dietary items -like "refresco," "carne," and "agua" - may be used in nutritionally contradictory ways between clinicians and Mexican immigrant patients. Specifically, the term "traditional food" in nutritional advice for Mexican migrants may be intended to promote consumption of fresh produce or less meat; but it may also invoke other foods (e.g., meats or corn), inspire more regular consumption of formerly rare foods (e.g., meats, flavored waters), or set up financially impossible goals (e.g., leaner meats than can be afforded). Salience studies with ethnographic follow up in target populations can promote the most useful and accurate terms for dietary advice.


Diphenylprolinol methyl ether: a highly enantioselective catalyst for Michael addition of aldehydes to simple enones.
[reaction: see text] Diphenylprolinol methyl ether catalyzes intermolecular Michael addition of simple aldehydes to relatively nonactivated enones with the highest enantioselectivities reported to date (95-99% ee) and significantly lower catalyst loadings than have been typical in this arena.


Determinants and prognostic value of albuminuria in adult patients with congenital heart disease.
The determinants and prognostic value of albuminuria remain unclear in patients with adult congenital heart disease (ACHD), especially in those with Fontan circulation (FC). We retrospectively reviewed 512 consecutive ACHD patients and investigated the determinants of urinary albumin-to-creatinine ratio (ACR) and albuminuria (MAU) and their association with all-cause mortality. Demographic data and laboratory and hemodynamic parameters were collected. Regression analysis and Cox proportional hazard models were used to identify the relationship between log ACR and variables, and clinical factors and all-cause mortality, respectively. Body mass index, aortic systolic blood pressure (ASP), arterial oxygen saturation (SaO2), glycated hemoglobin (HbA1c), B-type natriuretic peptide, and diuretic use were independently associated with log ACR. ASP, SaO2, and HbA1c were independently associated with MAU (P < .05-0.001). The prevalence of MAU was highest in unrepaired patients with low SaO2 (50%; P < .0001). Log ACR and MAU were associated with exercise capacity and all-cause mortality (P < .0001 for both) independent of renal function. Patients with ACHD, MAU, and renal dysfunction (n = 23) had the highest risk of all-cause mortality, while those without MAU or renal dysfunction had the lowest risk (P < .0001). These prognostic values remained significant in separate analyses of Fontan and biventricular circulation (P < .0001). ASP, SaO2, and HbA1c levels were independently associated with MAU in ACHD patients. MAU and log ACR were associated with all-cause mortality in patients with Fontan and biventricular circulation, independent of renal dysfunction.