Optimizing Child Nutrition Education With the Foodbot Factory Mobile Health App: Formative Evaluation and Analysis.
Early nutrition interventions to improve food knowledge and skills are critical in enhancing the diet quality of children and reducing the lifelong risk of chronic disease. Despite the rise of mobile health (mHealth) apps and their known effectiveness for improving health behaviors, few evidence-based apps exist to help engage children in learning about nutrition and healthy eating. This study aimed to describe the iterative development and user testing of Foodbot Factory, a novel nutrition education gamified app for children to use at home or in the classroom and to present data from user testing experiments conducted to evaluate the app. An interdisciplinary team of experts in nutrition, education (pedagogy), and game design led to the creation of Foodbot Factory. First, a literature review and an environmental scan of the app marketplace were conducted, and stakeholders were consulted to define the key objectives and content of Foodbot Factory. Dietitian and teacher stakeholders identified priority age groups and learning objectives. Using a quasi-experimental mixed method design guided by the Iterative Convergent Design for Mobile Health Usability Testing approach, five app user testing sessions were conducted among students (ages 9-12 years). During gameplay, engagement and usability were assessed via direct observations with a semistructured form. After gameplay, qualitative interviews and questionnaires were used to assess user satisfaction, engagement, usability, and knowledge gained. The environmental scan data revealed that few evidence-based nutrition education apps existed for children. A literature search identified key nutrients of concern for Canadian children and techniques that could be incorporated into the app to engage users in learning. Foodbot Factory included characters (2 scientists and Foodbots) who initiate fun and engaging dialogue and challenges (minigames), with storylines incorporating healthy eating messages that align with the established learning objectives. A total of five modules were developed: drinks, vegetables and fruit, grain foods, animal protein foods, and plant protein foods. Seven behavior change techniques and three unique gamified components were integrated into the app. Data from each user testing session were used to inform and optimize the next app iteration. The final user testing session demonstrated that participants agreed that they wanted to play Foodbot Factory again (12/17, 71%), that the app is easy to use (12/17, 71%) and fun (14/17, 88%), and that the app goals were clearly presented (15/17, 94%). Foodbot Factory is an engaging and educational mHealth intervention for the Canadian public that is grounded in evidence and developed by an interdisciplinary team of experts. The use of an iterative development approach is a demonstrated method to improve engagement, satisfaction, and usability with each iteration. Children find Foodbot Factory to be fun and easy to use, and can engage children in learning about nutrition.


Potassium ions and insulin release.
This article briefly reviews the effects of potassium on insulin release. Omission of extracellular potassium in vitro is followed by a delayed impairment of the release. At low concentrations of potassium, the insulinotropic effect of glucose is reduced in vivo and in vitro. In vivo, high concentrations of potassium increase insulin secretion, but, in vitro, supraphysiological concentrations of the ion first activate and then inactivate the releasing process.


Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis.
Despite the wide administration of several effective vaccines, rotavirus (RV) remains the single most important etiological agent of severe diarrhea in infants and young children worldwide, with an annual mortality of over 200,000 people. RV attachment and internalization into target cells is mediated by its outer capsid protein VP4. To better understand the molecular details of RV entry, we performed tandem affinity purification coupled with high-resolution mass spectrometry to map the host proteins that interact with VP4. We identified an actin-binding protein, drebrin (DBN1), that coprecipitates and colocalizes with VP4 during RV infection. Importantly, blocking DBN1 function by siRNA silencing, CRISPR knockout (KO), or chemical inhibition significantly increased host cell susceptibility to RV infection. Dbn1 KO mice exhibited higher incidence of diarrhea and more viral antigen shedding in their stool samples compared with the wild-type littermates. In addition, we found that uptake of other dynamin-dependent cargos, including transferrin, cholera toxin, and multiple viruses, was also enhanced in DBN1-deficient cells. Inhibition of cortactin or dynamin-2 abrogated the increased virus entry observed in DBN1-deficient cells, suggesting that DBN1 suppresses dynamin-mediated endocytosis via interaction with cortactin. Our study unveiled an unexpected role of DBN1 in restricting the entry of RV and other viruses into host cells and more broadly to function as a crucial negative regulator of diverse dynamin-dependent endocytic pathways.


Fetal cor triatriatum dexter: a report of two cases associated with nuchal edema in early second trimester.
Two early-2nd-trimester fetuses were aborted as a result of nuchal edema and suspected severe heart malformation. At autopsy one fetus demonstrated nuchal edema, mild hydronephrosis, and cor triatriatum dexter associated with ventricular septal defect and tubular hypoplasia of the aortic arch. The other fetus demonstrated severe nuchal edema, and cor triatriatum dexter was the only malformation. Cor triatriatum dexter is a rare cardiac malformation characterized by division of the right atrium into 2 compartments by a usually fenestrated membrane representing remnants of the right valve of the embryonic sinus venosus. This malformation has been diagnosed in adults and children by echocardiography, surgery, or autopsy but has not previously been published in fetuses.


The risk of contracting pediatric inflammatory bowel disease in children with celiac disease, epilepsy, juvenile arthritis and type 1 diabetes--a nationwide study.
The association of celiac disease with inflammatory bowel disease (IBD) in children is unclear. This study assesses the risk of IBD in children diagnosed with celiac disease and three other chronic diseases, namely epilepsy, juvenile idiopathic arthritis (JIA) and type 1 diabetes using nationwide, comprehensive registers. We identified Finnish children born between 1994 and 2008 and diagnosed with IBD (n=596) by October 2010 (aged up to 16 years) in a national register of medical reimbursements, which all these patients are entitled to. The presence of other chronic diseases, such as celiac disease, epilepsy, JIA and type 1 diabetes, diagnosed before the diagnosis of IBD was accordingly identified in patients and their population-based, individually matched controls (n=2380). The data on chronic diseases are based on certificates including the diagnostic criteria. The risk of contracting IBD in children with a diagnosis of a chronic disease was analyzed using conditional logistic regression analysis. Chronic diseases were more common in children contracting IBD than in their matched controls (frequency of chronic diseases 5.9% and 1.0%, respectively, p<0.001). Celiac disease associated with later development of ulcerative colitis (p<0.01) but the association with Crohn's disease was less clear (p<0.05). For the other chronic diseases, association was seen only between epilepsy and ulcerative colitis (p<0.01). Pediatric patients with celiac disease or epilepsy have an increased risk of developing IBD during their childhood but the risk is not high. This finding warrants a thorough investigation of intestinal symptoms in these children.


Culturally competent and spiritually sensitive therapy with lesbian and gay Christians.
This article presents results from a retrospective qualitative study of 27 lesbian and gay (LG) Christians that examined religious and spiritual issues and resolutions. Participants were also asked to identify the necessary knowledge and skills that practitioners (social workers, therapists, pastoral care providers, and so on) working with clients who are coming out need to help such clients integrate their sexual orientation and religion or spirituality. By analyzing the stories of participants, the authors identified information to enhance practitioners' cultural competence and spiritual sensitivity. Themes identified as important were having a historical perspective, self-awareness, and a nonjudgmental attitude; expanding definitions; and understanding the power of words. Participants described both their negative and positive experiences in integrating their faith and sexual orientation, and offered pragmatic suggestions for LG Christians. Themes identified were reframing scripture and tradition, supportive pastoral relationships, affirming Christian communities, peer support, and educational resources. This article will increase practitioner understanding of how to support the integration of sexual orientation and Christianity for LG clients who are coming out. It is also a resource for LG Christians who can benefit from reading stories of those who have successfully integrated their faith and sexual orientation.


Apoptotic and antiapoptotic effects of CXCR4: is it a matter of intrinsic efficacy? Implications for HIV neuropathogenesis.
CXCR4, the specific receptor for the chemokine SDF-1 alpha that also binds CXCR4-using HIV gp120s, affects survival of different cell types, including neurons. However, current data show that the outcome of CXCR4 activation on neuronal survival may vary depending on the ligand and/or the cellular conditions. In this study, we have systematically compared the effects of SDF-1 alpha and gp120(IIIB) (with or without CD4) on several intracellular pathways involved in cell survival, including MAP kinases and Akt-dependent pathways. Our data show that gp120(IIIB) and SDF-1 alpha are both potent activators of MAP kinases in neuronal and non-neuronal cells, though the kinetic of these responses is slightly different. Furthermore, unlike SDF-1 alpha, and independently of CD4, gp120(IIIB) is unable to stimulate Akt and some of its antiapoptotic targets (NF-kappa B and MDM2)--despite its ability to activate other signaling pathways in the same conditions. Finally, the viral protein is more efficient in recruiting some effectors (e.g., JNK) than others in comparison with SDF-1 alpha (EC(50) = 0.1 vs. 0.6 nM). We conclude that the intrinsic efficacy of the two ligands is significantly different and is pathway dependent. These findings have important implications for our understanding of CXCR4-mediated responses in the CNS, as well as the role of this coreceptor in HIV neuropathogenesis.


Brugada syndrome: an unusual cause of convulsive syncope.
A patient who presented with a new apparent seizure was found to have abnormal electrocardiographic findings, with classic features of the Brugada syndrome. He had spontaneous episodes of nonsustained ventricular tachycardia, easily inducible ventricular fibrillation at electrophysiological study in the absence of structural heart disease, and a negative neurological evaluation. These findings suggested that sustained ventricular arrhythmias known to be associated with the Brugada syndrome and resultant cerebral hypoperfusion, rather than a primary seizure disorder, were responsible for the event. Patients with the Brugada syndrome often present with sudden death or with syncope resulting from ventricular arrhythmias. In consideration of its variability in presentation sometimes mimicking other disorders, primary care physicians and internists should be aware of its often transient electrocardiographic features.


Association of maternal psychosocial stress with newborn body composition in the Healthy Start study.
Maternal psychosocial stress is associated with delivery of both small- and large-for-gestational-age newborns. Prior studies have relied on methods that do not capture fat mass (FM) vs. fat-free mass (FFM). We aimed to assess the relationship of maternal psychosocial stress, using the Edinburgh Postnatal Depression Scale (EPDS) and Cohen's Perceived Stress Scale (PSS), with newborn body composition. The sample included 604 mother/newborn pairs in the Healthy Start study. We used linear regression to examine associations of EPDS (>6.5 vs. ≤6.5) and PSS (>21 vs. ≤21) with newborn adiposity (FM and %FM measured by air displacement plethysmography [ADP], BMI-for-age, weight-for-length, and weight-for-age z-scores) and lean mass (FFM and length-for-age z-score). Average age of the women was 29.2 ± 6 y. Fifty-five percent of the women were white, 26.2% Hispanic, and 12.1% Black. Twenty-four percent of women had EPDS >6.5 and 18.1% had PSS >21. Mean ± SD birthweight was 3136 ± 437 g. After adjustment for confounders, EPDS >6.5 vs. ≤6.5 corresponded with 35.3 (95% CI: 6.6, 64.0) g lower offspring FM and 0.18 (-0.03, 0.39) units shorter length z-score. PSS was not associated with any neonatal outcomes. Maternal psychosocial stress is associated with delivery of shorter newborns with less FM.


Long Term Cardiovascular Outcome Based on Aspirin and Clopidogrel Responsiveness Status in Young ST-Elevated Myocardial Infarction Patients.
A subset of patients who take antiplatelet therapy continues to have recurrent cardiovascular events which may be due to antiplatelet resistance. The effect of low response to aspirin or clopidogrel on prognosis was examined in different patient populations. We aimed to investigate the prevalence of poor response to dual antiplatelet therapy and its relationship with major adverse cardiovascular events (MACE) in young patients with ST-elevation myocardial infarction (STEMI). In our study, we included 123 patients under the age of 45 with STEMI who underwent primary percutaneous intervention. A screening procedure to determine both aspirin and clopidogrel responsiveness was performed on the fifth day of admission. We followed a 2x2 factorial design and patients were allocated to one of four groups, according to the presence of aspirin and/or clopidogrel resistance. Patients were followed for a three-year period. A p-value less than 0.05 was considered statistically significant. We identified 48% of resistance against one or more antiplatelet in young patients with STEMI. More MACE was observed in patients with poor response to dual platelet therapy or to clopidogrel compared those with adequate response to the dual therapy (OR: 1.875, 1.144-3.073, p < 0.001; OR: 1.198, 0.957-1.499, p = 0.036, respectively). After adjustment for potential confounders, we found that poor responders to dual therapy had 3.3 times increased odds for three-year MACE than those with adequate response to the dual therapy. Attention should be paid to dual antiplatelet therapy in terms of increased risk for cardiovascular adverse events especially in young patients with STEMI.


Will the chemical probes please stand up?
In 2005, the NIH Molecular Libraries Program (MLP) undertook the identification of tool compounds to expand biological insights, now termed small-molecule chemical probes. This inspired other organisations to initiate similar efforts from 2010 onwards. As a central focus of the Probes & Drugs portal (P&D), we have standardised, integrated and compared sets of declared probe compounds harvested from 12 different sources. This turned out to be challenging and revealed unexpected anomalies. Results in this work address key questions including; a) individual and total structure counts, b) overlaps between sources, c) comparisons with selected PubChem sources and d) investigating the probe coverage of druggable targets. In addition, we developed new high-level scoring schemes to filter collections down to probes of higher quality. This generated 548 high-quality chemical probes (HQCP) covering 447 distinct protein targets. This HQCP collection has been added to the P&D portal and will be regularly updated as established sources expand and new ones release data.


Effects of the polyphenol content on the anti-diabetic activity of Cinnamomum zeylanicum extracts.
Cinnamomum zeylanicum is a popular kitchen spice widely investigated for insulin potentiating effects. Though a group of water soluble polyphenols belonging to the oligomeric procyanidins has been identified as the bioactive principle, the lack of systematic information on the effect of the polyphenol content on safety and anti-diabetic efficacy remains as a major limitation for the development of optimized and standardized cinnamon extracts for functional use. In the present paper, water soluble extracts of Cinnamomum zeylanicum containing 45 and 75% gallic acid equivalents (GAE) of polyphenol content were prepared by a novel process and characterized by tandem mass spectrometry. The polyphenol enhanced extracts were shown to be safe and offered better antioxidant potential, hypoglycemic effect, hypolipidimic effect, and significant decrease in other biochemical parameters as compared to the standard aqueous extract containing 15% GAE, when administered to streptozotocin-induced diabetic rats at 200 mg per kg b.w. for 30 days. The efficacy of polyphenol extracts in lowering blood glucose levels and ameliorating oxidative stress was further demonstrated in humans by administrating 'procynZ-45' containing 45% GAE polyphenols at a relatively low dosage of (125 mg × 2) per day for 30 days to 15 volunteers who had elevated fasting blood glucose levels; but not involved in any medication.


Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: a systematic review and meta-analysis of 1471 patients with solid tumors.
The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes. We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios (HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival (PFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/recurrence-free survival (RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type. A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS/DFS/MFS/RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74-3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49-2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, cancer type, and study type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58-4.44, P < 0.001) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50-4.22, P < 0.001) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis. CTC-WBC clusters are negative predictors for OS and PFS/DFS/MFS/RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.


Falling estradiol levels as a result of intentional reduction in gonadotrophin dose are not associated with poor IVF outcomes, whereas spontaneously falling estradiol levels result in low clinical pregnancy rates.
Although estradiol levels remain an integral part of monitoring in most IVF programmes, the effect of falling estradiol on IVF outcome has not been adequately quantified. The objective of this study was to evaluate the effect of falling estradiol levels prior to hCG on IVF outcome. This was a retrospective cohort study carried out in a university-based fertility clinic. A total of 112 IVF patients in whom estradiol levels fell prior to the administration of hCG were matched for age and year of treatment with 112 control IVF patients. IVF outcomes including oocytes retrieved, fertilization rate, embryos for transfer, and pregnancy rates were compared between the groups. Seventy per cent of women in the falling estradiol group experienced spontaneously falling estradiol levels. Spontaneously falling estradiol was associated with fewer oocytes retrieved (median 5 versus 8, P=0.001), increased rates of failed fertilization (18 versus 6%, P=0.018) and lower clinical pregnancy rates (12 versus 26%, P=0.012) compared to controls. Despite marked decreases in estradiol levels, IVF outcomes for patients whose estradiol levels fell as a result of deliberate protocol modification had similar fertilization and clinical pregnancy rates as controls. Subtle (<10%) spontaneous decreases in estradiol levels are associated with very poor IVF outcomes.


Providing psychiatric backup to family physicians by telephone.
To examine whether links between psychiatric services and family physicians can be strengthened and additional support provided for family physicians if a psychiatrist is available by phone to respond to clinical calls from family physicians. A psychiatrist, who visited 18 family physicians in 5 practices on a regular basis to provide clinical consultations, was available to provide telephone backup concerning mental health problems the family physicians encountered. All calls received by the psychiatrist were documented and analysed at the end of a 12-month period. Over the course of one year, 128 calls were received from the 5 practices. Fifty were considered urgent, while 78 involved more routine management or medication issues. Telephone advice enabled the family physicians to handle these cases more effectively, often reducing utilization of other mental health services and providing support that was not otherwise available. The average time spent per call was 8 minutes, which meant the psychiatrist was only spending 20 minutes per week on the phone responding to family physicians' requests. Providing telephone backup to family physicians is a time-efficient and effective method of supporting family physicians and reducing utilization of mental health services. It is applicable to psychiatrists working in any clinical setting.


In vitro and in vivo assessement of the antimalarial activity of sergeolide.
The antimalarial activity of sergeolide (a quassinoid from PICROLEMMA PSEUDOCOFFEA) was investigated both, IN VITRO on PLASMODIUM FALCIPARUM cultures and IN VIVO through a classical test of schizontocidal action against PLASMODIUM BERGHEI in mice. Sergeolide showed a very strong antiplasmodial activity IN VITRO as well as IN VIVO. Low concentrations (0.006 microg/ml) were able to fully inhibit the IN VITRO growth of chloroquine-sensitive and resistant strains of P. FALCIPARUM. Small amounts (0.26 mg/kg/day) markedly reduced the virulence of experimentally induced P. BERGHEI infection in mice. However, sergeolide, because of its high toxicity (LD 50: 1.8 mg/kg), does not seem, in its present form to be useful for malaria curative treatment.


Leptin and other components of the Metabolic Syndrome in Mauritius--a factor analysis.
To use factor analysis to examine the putative role of leptin in the Metabolic Syndrome, and to define better the associations among observed variables and the identified factors. Factor analysis of cross-sectional data from a 1987 survey. Non-diabetic residents of Mauritius who participated in population-based surveys in 1987 and 1992 (1414 men and 1654 women). Fasting and 2 h plasma glucose and insulin following a 75 g oral glucose load; seated blood pressure; body mass index (BMI); waist-to-hip ratio (WHR); and fasting serum triglycerides, HDL-cholesterol, leptin and uric acid concentrations. Principal components factor analysis revealed three factors for men and women that explained between 54 and 55% of the observed variance of the 12 measured variables. General features of these factors were as follows: factor 1, WHR, BMI, leptin, fasting and 2 h insulin, triglycerides, and HDL-cholesterol; factor 2, systolic and diastolic blood pressure, uric acid (men only), and fasting glucose (women only); and factor 3, fasting and 2 h glucose and insulin. Only three variables loaded on more than one factor with a loading > or = 0.4 (fasting and 2 h insulin, fasting glucose in women only). Leptin loaded on one factor only in both men and women. Since multiple factors underlie the Metabolic Syndrome, and since no observed variable loads on all three factors, more than one mechanism might account for the observed clustering of risk characteristics. Leptin does not unite features of this syndrome due to its loading on one factor only. Uric acid is related to a different factor in men and women. The absence of gender differences in factor loadings argues for similar mechanisms for the Metabolic Syndrome in men and women in Mauritius. International Journal of Obesity (2001) 25, 126-131


A Josephson radiation comb generator.
We propose the implementation of a Josephson Radiation Comb Generator (JRCG) based on a dc superconducting quantum interference device (SQUID) driven by an external magnetic field. When the magnetic flux crosses a diffraction node of the critical current interference pattern, the superconducting phase undergoes a jump of π and a voltage pulse is generated at the extremes of the SQUID. Under periodic drive this allows one to generate a sequence of sharp, evenly spaced voltage pulses. In the frequency domain, this corresponds to a comb-like structure similar to the one exploited in optics and metrology. With this device it is possible to generate up to several hundreds of harmonics of the driving frequency. For example, a chain of 50 identical high-critical-temperature SQUIDs driven at 1 GHz can deliver up to a 0.5 nW at 200 GHz. The availability of a fully solid-state radiation comb generator such as the JRCG, easily integrable on chip, may pave the way to a number of technological applications, from metrology to sub-millimeter wave generation.


Clinical comparison of piperacillin and cefoxitin in patients with bacteriologically confirmed infections.
The objective of this double-blind study was to compare the efficacy and safety of piperacillin with that of cefoxitin in patients with bacterial infections. Seventy hospitalized patients were treated with intravenous piperacillin (18 g/day) or cefoxitin (12 g/day) for a mean period of 11.5 days. Multiple serious underlying conditions were present in 91% of the patients in both treatment groups. The infection sites were the respiratory, urinary, and gastrointestinal tracts, the skin and skin structures, and the bones. Among the patients with evaluated courses of therapy, 87% (20 of 23) of the patients in the piperacillin-treated group and 90% (19 of 21) of the cefoxitin-treated patients were cured or improved. Multiple sites of infection were present in 6 patients given piperacillin and in 11 patients given cefoxitin. Gram-negative aerobic bacteria were the most frequently isolated organisms (56% of isolates). In each treatment group, 91% of the pathogens were eradicated. Three piperacillin-treated patients (9%) and four cefoxitin-treated patients (11%) had adverse clinical effects related to therapy; most of the effects were moderate in intensity. In conclusion, both piperacillin and cefoxitin were clinically safe and effective antibiotics for the treatment of these patients, most of whom had severe underlying conditions.


[CD103+CD8+T cells combined with neutrophil-to-lymphocyte ratio predict response to neoadjuvant chemoimmunotherapy in advanced oral squamous cell carcinoma].
Objective: To investigate the relationship between the expression of CD103+CD8+T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods: Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103+CD8+T cells and the efficacy of NACI. CD103+CD8+T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103+CD8+T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It's effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results: The density of CD103+CD8+T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103+CD8+T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm2 and 21.63(4.91, 71.92) pcs/mm2 respectively, with statistically significant differences(U=52.00, P=0.012). CD103+CD8+T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII (P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 (P=0.009, 95%CI: 0.5715-0.9910), 0.671 (P=0.105, 95%CI: 0.467-0.881), 0.679 (P=0.020 95%CI: 0.549-0.951), 0.750 (P=0.096, 95%CI: 0.461-0.896), respectively. The AUC for CD103+CD8+T cells alone was 0.861 (P=0.013, 95%CI: 0.585-0.950), and the AUC of combining CD103+CD8+T cells with NLR was 0.896 (P=0.025, 95%CI: 0.454-0.938). Conclusions: The density of CD103+CD8+T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103+CD8+T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103+CD8+T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.


Redox Regulation of the Mitochondrial Quality Control Protease Oma1.
Aims: Normal mitochondrial function and integrity are crucial for cellular physiology. Given the paramount role of mitochondrial quality control proteases in these processes, our study focused on investigating mechanisms by which the activity of a key quality control protease Oma1 is regulated under normal conditions and in response to homeostatic insults. Results: Oma1 was found to be a redox-dependent protein that exists in a semi-oxidized state in yeast and mammalian mitochondria. Biochemical and genetic analyses provide evidence that activity and stability of the Oma1 oligomeric complex can be dynamically tuned in a reduction/oxidation-sensitive manner. Mechanistically, these features appear to be mediated by two intermembrane space (IMS)-exposed highly conserved cysteine residues, Cys272 and Cys332. These residues form a disulfide bond, which likely plays a structural role and influences conformational stability and activity of the Oma1 high-mass complex. Finally, in line with these findings, engineered Oma1 substrate is shown to engage with the protease in a redox-sensitive manner. Innovation: This study provides new insights into the function of the Oma1 protease, a central controller of mitochondrial membrane homeostasis and dynamics, and reveals the novel conserved mechanism of the redox-dependent regulation of Oma1. Conclusion: Disulfide bonds formed by IMS-exposed residues Cys272 and Cys332 play an important evolutionarily conserved role in the regulation of Oma1 function. We propose that the redox status of these cysteines may act as a redox-tunable switch to optimize Oma1 proteolytic function for specific cellular conditions or homeostatic challenges.


Gene-specific repression of the p53 target gene PUMA via intragenic CTCF-Cohesin binding.
The p53 transcriptional program orchestrates alternative responses to stress, including cell cycle arrest and apoptosis, but the mechanism of cell fate choice upon p53 activation is not fully understood. Here we report that PUMA (p53 up-regulated modulator of apoptosis), a key mediator of p53-dependent cell death, is regulated by a noncanonical, gene-specific mechanism. Using chromatin immunoprecipitation assays, we found that the first half of the PUMA locus (approximately 6 kb) is constitutively occupied by RNA polymerase II and general transcription factors regardless of p53 activity. Using various RNA analyses, we found that this region is constitutively transcribed to generate a long unprocessed RNA with no known coding capacity. This permissive intragenic domain is constrained by sharp chromatin boundaries, as illustrated by histone marks of active transcription (histone H3 Lys9 trimethylation [H3K4me3] and H3K9 acetylation [H3K9Ac]) that precipitously transition into repressive marks (H3K9me3). Interestingly, the insulator protein CTCF (CCCTC-binding factor) and the Cohesin complex occupy these intragenic chromatin boundaries. CTCF knockdown leads to increased basal expression of PUMA concomitant with a reduction in chromatin boundary signatures. Importantly, derepression of PUMA upon CTCF depletion occurs without p53 activation or activation of other p53 target genes. Therefore, CTCF plays a pivotal role in dampening the p53 apoptotic response by acting as a gene-specific repressor.


Toxoplasmosis in Germany.
With approximately 30% of the world population infected, Toxoplasma gondii is one of the most widespread pathogenic parasites in both humans and animals and a major problem for health economics in many countries. This review is based on the findings of individual studies, meta-analyses, and Cochrane Reviews retrieved by a selective literature survey of the Medline and Google Scholar databases. Current data indicate a high rate of Toxoplasma gondii infection in Germany, ranging from 20% to 77% depending on age (95% confidence interval for 18- to 29-year-olds [17.0; 23.1]; for 70- to 79-year-olds [72.7; 80.5]). Male sex, caring for a cat, and a body mass index of 30 or more are independent risk factors for seroconversion. Postnatally acquired (food-related) infec- tion is predominant, but maternal-to-fetal transmission still plays an important role. While most infections are asymptomatic, congenital toxoplasmosis and reactivated Toxoplasma encephalitis in immunosuppressed persons (transplant recipients and others) are sources of considerable morbidity. Toxoplasma gondii infection of the retina is the most common cause of infectious uveitis in Germany. The diagnosis and treatment of this type of parasitic infection are particular to the specific organs involved in the individual patient. Desirable steps for the near future include development of an effective treatment for the cystic stage and identifica- tion of biomarkers to assess the risk of reactivation and predict the disease course.


DNA barcoding of native Caucasus herbal plants: potentials and limitations in complex groups and implications for phylogeographic patterns.
DNA barcoding has rapidly become a useful complementary tool in floristic investigations particularly for identifying specimens that lack diagnostic characters. Here, we assess the capability of three DNA barcode markers (chloroplast rpoB, accD and nuclear ITS) for correct species assignment in a floristic survey on the Caucasus. We focused on two herbal groups with potential for ornamental applications, namely orchids and asterids. On these two plant groups, we tested whether our selection of barcode markers allows identification of the "barcoding gap" in sequence identity and to distinguish between monophyletic species when employing distance-based methods. All markers successfully amplified most specimens, but we found that the rate of species-level resolution amongst selected markers largely varied in the two plant groups. Overall, for both lineages, plastid markers had a species-level assignment success rate lower than the nuclear ITS marker. The latter confirmed, in orchids, both the existence of a barcoding gap and that all accessions of the same species clustered together in monophyletic groups. Further, it also allowed the detection of a phylogeographic signal.The ITS marker resulted in its being the best performing barcode for asterids; however, none of the three tested markers showed high discriminatory ability. Even if ITS were revealed as the most promising plant barcode marker, we argue that the ability of this barcode for species assignment is strongly dependent on the evolutionary history of the investigated plant lineage.


Neural-network control of mobile manipulators.
In this paper, a neural network (NN)-based methodology is developed for the motion control of mobile manipulators subject to kinematic constraints. The dynamics of the mobile manipulator is assumed to be completely unknown, and is identified online by the NN estimators. No preliminary learning stage of NN weights is required. The controller is capable of disturbance-rejection in the presence of unmodeled bounded disturbances. The tracking stability of the closed-loop system, the convergence of the NN weight-updating process and boundedness of NN weight estimation errors are all guaranteed. Experimental tests on a 4-DOF manipulator arm illustrate that the proposed controller significantly improves the performance in comparison with conventional robust control.


Clinical predictors of all-cause mortality in patients presenting to specialist heart failure clinic with raised NT-proBNP and no heart failure.
Clinical outcomes for patients suspected of having heart failure (HF) who do not meet the diagnostic criteria of any type of HF by echocardiography remain unknown. The aim of this study was to investigate the clinical predictors of all-cause mortality in patients with suspected HF, a raised N-terminal pro-b-type natriuretic peptide (NTproBNP) and who do not meet the diagnostic criteria of any type of HF by echocardiography. Relevant data were taken from the Sheffield HEArt Failure (SHEAF) registry (222349P4). The inclusion criteria were presence of symptoms raising suspicion of HF, NTproBNP > 400 pg/mL, and preserved left ventricular function. Exclusion criteria were any type of HF by echocardiography. The outcome was defined as all-cause mortality. Cox proportional-hazards regression model was used to investigate the association between the survival time of patients and clinical variables; 1031 patients were identified with NTproBNP > 400 pg/mL but who did not have echocardiographic evidence of HF. All-cause mortality was 21.5% (222 deaths) over the mean follow-up (FU) period of 6 ± 2 years. NTproBNP was similar in patients who were alive or dead (P = 0.96). However, age (HR 1, P < 0.01), chronic kidney disease (CKD, HR 1.2, P < 0.01), chronic pulmonary obstructive disease (COPD, HR 1.6, P < 0.01), dementia (HR 5.9, P < 0.01), male gender (HR 1.4, P < 0.01), first-degree atrioventricular block (HR 2.1, P < 0.01), left axis deviation (HR 1.6, P = 0.04), and diabetes (HR 1.4, P = 0.03) were associated with all-cause mortality. In multivariate regression, age, gender, CKD stage, COPD, and dementia were independently associated with mortality. In patients with NTproBNP > 627 pg/mL, NYHA class predicted death (II, 19.6%; III, 27.4%; IV, 66.7%; P < 0.01). Patients with no HF on echocardiography but raised NTproBNP suffer excess mortality particularly in the presence of certain clinical variables. Age, male gender, worsening CKD stage, presence of COPD, and dementia are independently associated with all-cause mortality in these patients. An NTproBNP > 627 pg/mL coupled with NYHA class could identify patients at greatest risk of death.


Development of the Juvenile Justice Anger Management Treatment for Girls.
Female juvenile offenders exhibit high levels of anger, relational aggression, and physical aggression, but the population has long been ignored in research and practice. No anger management treatments have been developed specifically for this population, and no established anger management treatments are empirically supported for use with delinquent girls. Thus, to alleviate anger and reduce the frequency and severity of aggressive behaviors in this underserved population, we developed the gender-specific, Juvenile Justice Anger Management (JJAM) Treatment for Girls. This cognitive-behavioral intervention was adapted from the Coping Power Program (Lochman & Wells, 2002), a school-based anger management treatment for younger children that has established efficacy and effectiveness findings with its target populations. This paper describes how the content of JJAM was developed to meet the unique needs of adolescent girls in residential juvenile justice placements. It also traces the process of developing a manualized treatment and the steps taken to enhance efficacy and clinical utility. An overview of the treatment, a session-by-session outline, an example session activity, and an example homework assignment are provided. A randomized controlled trial is currently being conducted to evaluate the efficacy of the JJAM Treatment for Girls.


Bacteriophage Taxonomy: A Continually Evolving Discipline.
While taxonomy is an often underappreciated branch of science, it serves very important roles. Bacteriophage taxonomy has evolved from a discipline based mainly on morphology, characterized by the work of David Bradley and Hans-Wolfgang Ackermann, to the sequence-based approach that is taken today. The Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) takes a holistic approach to classifying prokaryote viruses by measuring overall DNA and protein similarity and phylogeny before making decisions about the taxonomic position of a new virus. The huge number of complete genomes being deposited with the National Center for Biotechnology Information (NCBI) and other public databases has resulted in a reassessment of the taxonomy of many viruses, and the future will see the introduction of new viral families and higher orders.


Socio-spatial mobilities and narratives of class identity in Britain.
In this article we carry out the most comprehensive analysis of social and spatial mobility in the UK to date and the first to directly link different dimensions of mobility to processes of social class formation. Using new analytical techniques in this field, we integrate quantitative and qualitative data from the 1958 Birth Cohort Study, combining text-mining and correspondence analysis in order to examine the intersection of geographical and social mobility with class identities. This work reflects a revival of interest in the spatialization of class inequalities, which is connected to policy concerns about the regional dimension of Britain's mobility 'crisis' that have intensified in the wake of the 'Brexit' vote. We find that the South's role as an 'escalator' region for upward mobility has continued and that the relationship between social and spatial mobility both confirms and qualifies the role of London and the South East in generating inequalities. We show that different migration-mobility transitions are associated with distinctive and contrasting class identity narratives. Those who move from North to South stand out in particular for the way their 'class talk' reveals the social disorientation that attends their success. The contrasting ways in which other groups express their social identities suggests that the interplay of geographical and social mobilities performs a significant role in regional cultural divisions.


Amino acid uptake by kidney and jejunal tissue from dogs with cystine stones.
Cystine and lysine accumulation in vitro in intestinal and renal tissue was studied in eight dogs that form cystine stones. Under conditions which demonstrate in vitro defects in tissue obtained from humans with cystinuria, normal amino acid accumulation occurred in six dogs with the canine disorder. Normal amino acid uptake in tissue and the demonstration of normal to minimum increases in excretion of lysine suggest that the canine disorder is not similar to the human syndrome.


Knowledge transfer and exchange processes for environmental health issues in Canadian Aboriginal communities.
Within Canadian Aboriginal communities, the process for utilizing environmental health research evidence in the development of policies and programs is not well understood. This fundamental qualitative descriptive study explored the perceptions of 28 environmental health researchers, senior external decision-makers and decision-makers working within Aboriginal communities about factors influencing knowledge transfer and exchange, beliefs about research evidence and Traditional Knowledge and the preferred communication channels for disseminating and receiving evidence. The results indicate that collaborative relationships between researchers and decision-makers, initiated early and maintained throughout a research project, promote both the efficient conduct of a study and increase the likelihood of knowledge transfer and exchange. Participants identified that empirical research findings and Traditional Knowledge are different and distinct types of evidence that should be equally valued and used where possible to provide a holistic understanding of environmental issues and support decisions in Aboriginal communities. To facilitate the dissemination of research findings within Aboriginal communities, participants described the elements required for successfully crafting key messages, locating and using credible messengers to deliver the messages, strategies for using cultural brokers and identifying the communication channels commonly used to disseminate and receive this type of information.


Impact of receiving blood cholesterol test results on dietary change.
The study objective was to determine the impact of receiving results of a blood cholesterol test on changes in dietary behaviors among individuals participating in a Health Risk Appraisal Program. This randomized trial of maintenance employees at six hospitals included two groups: Group 1 received their blood cholesterol test results at the pretest; Group 2 received results only at the posttest (16-20 weeks later). The pretest interview included (1) a 24-hour dietary recall; (2) an evaluation of dietary behaviors and suggestions on how to change; (3) height, weight, and blood cholesterol measurement. Five hundred employees participated, and 429 eligible employees completed both pretest and posttest interviews. Blood cholesterol levels decreased by 4.8% (P < .001) and saturated fat intake decreased by 7.4% (P < .05). Regression analyses indicated that individuals more likely to have lowered saturated fat intake had higher pretest saturated fat intakes, had a family history of high blood cholesterol, and were light-maintenance employees (P < .05); no other variables were associated (receiving blood cholesterol test results, previous blood cholesterol test, pretest blood cholesterol levels, personal history of heart disease, BMI, age, gender, tobacco/alcohol use). Among subjects with normal cholesterol levels, those not receiving blood test results reduced saturated fat intake more than those receiving test results; both groups had similar saturated fat intakes (> 12%) greater than recommended intake (< 10%). Screening programs should include an assessment of saturated fat intake as screening for blood cholesterol may provide normocholesterolemic subjects with a false sense of security.


MENA-SINO Consensus Statement on Implementing Care Pathways for Acute Neurovascular Emergencies During the COVID-19 Pandemic.
In the unprecedented current era of the COVID-19 pandemic, challenges have arisen in the management and interventional care of patients with acute stroke and large vessel occlusion, aneurysmal subarachnoid hemorrhage, and ruptured vascular malformations. There are several challenges facing endovascular therapy for stroke, including shortages of medical staff who may be deployed for COVID-19 coverage or who may have contracted the infection and are thus quarantined, patients avoiding early medical care, a lack of personal protective equipment, delays in door-to-puncture time, anesthesia challenges, and a lack of high-intensity intensive care unit and stroke ward beds. As a leading regional neurovascular organization, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) has established a task force composed of medical staff and physicians from different disciplines to establish guiding recommendations for the implementation of acute care pathways for various neurovascular emergencies during the current COVID-19 pandemic. This consensus recommendation was achieved through a series of meetings to finalize the recommendation.


Major depressive disorder in coronary artery disease.
Depression has been reported to be common in patients with coronary artery disease (CAD), using a variety of criteria for the diagnosis of depression. However, many studies have relied solely on the presence of symptoms such as a dysphoric mood and fatigue in making a diagnosis of depression. Both fatigue and dysphoric mood are also associated with medical illnesses, and psychiatric diagnoses based on such nonspecific symptoms may lack the specificity necessary to predict the need for psychiatric treatment. To assess the incidence of depression likely to require and respond to psychiatric treatment, 50 patients documented to have CAD by coronary angiography underwent psychiatric diagnostic interviews. Current research-based criteria (DSM-III) were used to make diagnoses of major depressive disorder. In addition, the applicability of a brief screening inventory the (Beck depression inventory) for detecting the presence of depression in these patients was tested. Nine patients (18%) met criteria (DSM-III) for major depressive episode. Depression was not related to the extent of CAD, age or use of beta blockers. There was a relation between depression and smoking. Only 2 of the 9 depressed patients had been diagnosed previously and were being treated for depression. When a score of greater than or equal to 10 on the Beck depression inventory was used to distinguish patients with depression, it had moderate sensitivity (78%) and specificity (90%) for the identification of depression.


Phylogenomic inferences from reference-mapped and de novo assembled short-read sequence data using RADseq sequencing of California white oaks (Quercus section Quercus).
The emergence of next generation sequencing has increased by several orders of magnitude the amount of data available for phylogenetics. Reduced representation approaches, such as restriction-sited associated DNA sequencing (RADseq), have proven useful for phylogenetic studies of non-model species at a wide range of phylogenetic depths. However, analysis of these datasets is not uniform and we know little about the potential benefits and drawbacks of de novo assembly versus assembly by mapping to a reference genome. Using RADseq data for 83 oak samples representing 16 taxa, we identified variants via three pipelines: mapping sequence reads to a recently published draft genome of Quercus lobata, and de novo assembly under two sets of locus filters. For each pipeline, we inferred the maximum likelihood phylogeny. All pipelines produced similar trees, with minor shifts in relationships within well-supported clades, despite the fact that they yielded different numbers of loci (68 000 - 111 000 loci) and different degrees of overlap with the reference genome. We conclude that both the reference-aligned and de novo assembly pipelines yield reliable results, and that advantages and disadvantages of these approaches pertain mainly to downstream uses of RADseq data, not to phylogenetic inference per se.


The irony of chirality - unveiling the distinct mechanistic binding and activities of 1-(3-(4-amino-5-(7-methoxy-5-methylbenzo[b]thiophen-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidin-1-yl)prop-2-en-1-one enantiomers as irreversible covalent FGFR4 inhibitors.
The influence of chirality on the therapeutic activities of drug molecules has remained an interesting subject matter in drug design. The recent identification of two chiral irreversible inhibitors with differential inhibitory activities towards oncogenic fibroblast growth factor receptor 4 (FGFR4) presented an avenue to investigate the underlying mechanisms that accounted for their disparate activities. Accordingly, the S-configured form (9g) exhibited '15 times' potency than the corresponding R-configured (9h) form. Nonetheless, the big question remains how does chirality influence their inhibitory potencies? Therefore, in this study, we seek to provide useful insights into this interesting phenomenon using molecular dynamics simulations and free binding energy calculations. Interestingly, we observed that the inhibitory 9g activity correlates with a coordinated movement of the active site p-loop, as specifically induced by the S-configuration, which allowed the rotation of three dihedral angles; φ1(CNCO), φ2(CCC*N) and φ3(CCCC), thereby achieving optimal orientations suitable for interactions with crucial active site residues such as LEU473, LYS503, ASP641 and TYR643. Consequentially, while the 9h-bound FGFR4 active site was highly unstable, 9g exerted an inward pulling effect which accounted for active site stability and compactness. Also, the positional movement of 9h (R-configuration) at the active site was restricted, thereby preventing interactions with key residues. Moreover, 9g exhibited the most favorable binding as compared to 9h which showed a relatively lower ΔGbind. The higher binding affinity of 9g to FGFR4 can be mainly attributed to the increase in van der Waals energy by -4.12 kcal mol-1 and electrostatic by -2.89 kcal mol-1. The difference in van der Waals interactions is mainly determined by two residues; ASP641 and TYR643, whilst, the difference in electrostatic interactions is primarily determined by two residues LEU473 and LYS503.


Beneficial Effects of Qigong Wuqinxi in the Improvement of Health Condition, Prevention, and Treatment of Chronic Diseases: Evidence from a Systematic Review.
Qigong is a modality of traditional Chinese mind-body medicine that has been used to prevent and cure ailments, to improve health in China for thousands of years. Wuqinxi, a Chinese traditional Qigong that focuses on mind-body integration, is thought to be an effective exercise in promoting physical and mental wellbeing. Thus, we summarized the evidence and aim to unravel effects of Wuqinxi on health outcomes. We performed a systematic review of Wuqinxi studies published in English or Chinese since 1979. Relevant English and Chinese language electronic data bases were used for literature search. The selection of studies, data extraction, and validation were performed independently by two reviewers. A total of 28 eligible studies were included in this review, among which three are 3 in English and 25 in Chinese. The studies included in this review involve three different experimental designs: (1) 16 RCTs; (2) 2 historical cohort studies; and (3) 10 pretest and posttest studies (PPS). Participants in this review are categorized as either healthy or clinical populations. The results from this systematic review support the notion that Wuqinxi may be effective as an adjunctive rehabilitation method for improving psychological and physiological wellbeing among different age of healthy populations in addition to alleviating and treating diseases among various clinical populations. The results indicated that Wuqinxi has been thought to be beneficial to improve health and treat chronic diseases. However, the methodological problems in the majority of included studies make it difficult to draw firm conclusive statements. More methodologically rigorous designed large-scale RCTs with a long-term follow-up assessment should be further conducted to examine the effects of Wuqixi on health-related parameters and disease-specific measures in different health conditions. This systematic review lends insight for future studies on Wuqinxi and its potential application in preventive and rehabilitation medicine.


Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial.
Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient's resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, -14%, 95% CI, -25% to -2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality. Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction. clinicaltrials.gov Identifier: NCT01536470.


Distracted mobile device use among street-crossing college student pedestrians: an observational approach.
ObjectiveTo estimate the incidence of mobile device use among street-crossing pedestrians and explore differences by sex and intersection type at a large public South-eastern university in the United States.ParticipantsAll instances of campus pedestrians crossing the street during the observation period (N = 4,878).MethodsVideo recordings of crosswalk activity at four locations were analyzed for pedestrian use of a mobile device while crossing.ResultsDevice use while crossing was observed 1,201 (24.6%) times. Of male crossing instances, 277 (16.8%) were coded as using a device. Of female instances, 924 (28.6%) were coded as using a device. Differences in device use while crossing were found between sexes and some intersection types.ConclusionsThis study estimates mobile device use while crossing the street and suggests differences by sex and intersection type. Future research should focus on improving understanding of the problem and evaluation of interventions to address the issue.


Host Akkermansia muciniphila Abundance Correlates With Gulf War Illness Symptom Persistence via NLRP3-Mediated Neuroinflammation and Decreased Brain-Derived Neurotrophic Factor.
Neurological disorders are commonly reported among veterans who returned from the Gulf war. Veterans who suffer from Gulf War illness (GWI) complain of continued symptom persistence that includes neurological disorders, muscle weakness, headaches, and memory loss, that developed during or shortly after the war. Our recent research showed that chemical exposure associated microbial dysbiosis accompanied by a leaky gut connected the pathologies in the intestine, liver, and brain. However, the mechanisms that caused the symptoms to persist even 30 years after the war remained elusive to investigators. In this study, we used a rodent model of GWI to investigate the persistence of microbiome alterations, resultant chronic inflammation, and its effect on neurotrophic and synaptic plasticity marker BDNF. The results showed that exposure to GW chemicals (the pesticide permethrin and prophylactic drug pyridostigmine bromide) resulted in persistent pathology characterized by the low relative abundance of the probiotic bacteria Akkermansia muciniphila in the gut, which correlated with high circulatory HMGB1 levels, blood-brain barrier dysfunction, neuroinflammation and lowered neurotrophin BDNF levels. Mechanistically, we used mice lacking the NLRP3 gene to investigate this inflammasome's role in observed pathology. These mice had significantly decreased inflammation and a subsequent increase in BDNF in the frontal cortex. This suggests that a persistently low species abundance of Akkermansia muciniphila and associated chronic inflammation due to inflammasome activation might be playing a significant role in contributing to chronic neurological problems in GWI. A therapeutic approach with various small molecules that can target both the restoration of a healthy microbiome and decreasing inflammasome activation might have better outcomes in treating GWI symptom persistence.


Large-volume protein crystal growth for neutron macromolecular crystallography.
Neutron macromolecular crystallography (NMC) is the prevailing method for the accurate determination of the positions of H atoms in macromolecules. As neutron sources are becoming more available to general users, finding means to optimize the growth of protein crystals to sizes suitable for NMC is extremely important. Historically, much has been learned about growing crystals for X-ray diffraction. However, owing to new-generation synchrotron X-ray facilities and sensitive detectors, protein crystal sizes as small as in the nano-range have become adequate for structure determination, lessening the necessity to grow large crystals. Here, some of the approaches, techniques and considerations for the growth of crystals to significant dimensions that are now relevant to NMC are revisited. These include experimental strategies utilizing solubility diagrams, ripening effects, classical crystallization techniques, microgravity and theoretical considerations.


New medicine for the new millennium: a time for change?
Health care is under scrutiny. Demand exceeds supply and funding is insufficient. Rationing is a reality while providers feel persecuted. Yet patients remain patient--and continue to suffer. What can be done to improve the present situation?


Decreased functional connectivity by aging is associated with cognitive decline.
Aging is related to cognitive decline, and it has been reported that aging disrupts some resting state brain networks. However, most studies have focused on the default mode network and ignored other resting state networks. In this study, we measured resting state activity using fMRI and explored whether cognitive decline with aging is related to disrupted resting state networks. Independent component analysis was used to evaluate functional connectivity. Notably, the connectivity within the salience network that consisted of the bilateral insula and the anterior cingulated cortex decreased with aging; the impairment of functional connectivity was correlated with measured decreases in individual cognitive abilities. Furthermore, certain internetwork connectivities (salience to auditory, default mode to visual, etc.) also decreased with aging. These results suggest that (1) aging affects not only the default mode network but also other networks, specifically the salience network; (2) aging affects internetwork connectivity; and (3) disruption of the salience network is related to cognitive decline in elderly people.


[Jarcho-Levin syndrome associated with maternal hypothyroidism].
Jarcho Levin syndrome is an eponymous syndrome consisting with a set of multiple vertebral and rib anomalies, characterized by a short neck, short trunk and short height, which trigger respiratory failure and early neonatal death. The frequency and spectrum of morphological defects in the environment is unknown. This article reports a case. a female newborn, product of the third pregnancy in a woman of 29 years, with a history of three previous miscarriages; she had a twin pregnancy and hypothyroidism later. Prenatal ultrasound performed at 28-29 weeks of gestation showed polyhydramnios, mild duodenal atresia, likely annular pancreas, and agenesis of lumbar vertebrae. At birth, turreted skull, short neck, thoracoabdominal dissociation, anal stenosis, hypotrophic external genitalia, hypoplastic pelvic limbs, and popliteal hyperflexion were found. Imaging identified intestinal atresia, scoliosis, lumbar vertebrae agenesis, and defects of segmentation on fourth and fifth right ribs. Laparotomy confirmed malrotation of the small intestine and colon, and complete annular pancreas with Meckel diverticulum. this syndrome is a set of phenotypes derived from skeletal malformations and other defects. The outcome depends on the severity and quality.


Does a Surgical Post-Acute Unit Help Elders With Rib Fractures? Definitely Maybe!
A surgical post-acute treatment unit (SPA) was developed for acutely injured elderly patients who no longer warranted acute care in an intensive care setting to decrease complications by focusing increased bedside attention to cognition, nutrition, respiration, and mobilization. A retrospective review was performed comparing patients 65 years and older with isolated rib fractures treated before the SPA was opened with patients treated in the SPA. The 2 populations were comparable except the SPA group had a higher mean Injury Severity Score. Nine complications occurred in the pre-SPA group, and no complications occurred in the SPA patient population. Four patients in the pre-SPA group died compared with zero deaths for the SPA group. The rates of complications and mortality between elderly patients with isolated rib fractures were not statistically different between patients treated with a traditional admission to an inpatient ward and patients admitted to the SPA, even though the SPA patients had significantly more severe chest injuries. Establishing a physical environment to support the needs of elderly trauma patients with isolated rib fractures who no longer need the intensive care unit (ICU) is effective in decreasing the complications and unplanned returns to the ICU.


Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2.
The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8alpha(alpha) or the heterodimer alpha beta stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class I/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 A resolution of a complex between CD8alpha(alpha) and the human MHC molecule HLA-A2, which is associated with peptide. CD8alpha(alpha) binds one HLA-A2/peptide molecule, interfacing with the alpha2 and alpha3 domains of HLA-A2 and also contacting beta2-microglobulin. A flexible loop of the alpha3 domain (residues 223-229) is clamped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the alpha3 domain is different from that in uncomplexed HLA-A2, being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in alpha3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is clearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions.


The re-emergence of aerosol gene delivery: a viable approach to lung cancer therapy.
The long-term survival of lung cancer patients treated with conventional therapies (surgery, radiation therapy and chemotherapy) remains poor and has changed little in decades. The need for novel approaches remains high and gene therapy holds promise in this area. A number of genes have been shown in vitro, in animal studies and most recently, in human clinical trials, to have antitumor actions. However, a number of problems still exist and success in human patients to date has been marginal. Among the numerous considerations are the efficiency of delivery of the gene to the tumor or, if an indirect effect is the aim, possibly nontumor tissues, the efficiency and persistence of expression of the therapeutic gene, the specificity of the gene action against the tumor, potential toxic or pathogenic consequences of either the genes or the delivery vectors used, convenience of the therapy and how likely the therapy will compliment or complicate other conventional anticancer therapies. After the cloning of the cystic fibrosis gene, there was great interest in the noninvasive delivery of genes directly to the pulmonary surfaces by aerosol. Clearly, this approach could have application to some pulmonary cancers as well and most early efforts focused mainly on the use of nonviral vectors, primarily cationic lipids. Unfortunately, nebulization shear forces and inefficient pulmonary uptake and expression of plasmid DNA-cationic lipid formulations have generally resulted in a lack of therapeutic effect, so much of this work has diminished in recent years. Polyethyleneimine (PEI)-based formulations have proven stable during nebulization and result in nearly 100% efficient transfection throughout the airways and lung parenchyma. Therapeutic responses have been obtained in several animal lung tumor models when PEI-based formulations of p53 and other antitumor genes were delivered by aerosol. In addition, this mode of delivery seems to be associated with low toxicity and results in little or none of the immunostimulatory response typically associated with the delivery of bacterially produced plasmid DNA containing unmethylated CpG motifs, which has presented a challenge to repeated gene therapy via other modes of delivery. Other potential applications of PEI aerosol gene delivery include the treatment of asthma, lung alveolitis and fibrosis and a variety of monogeneic diseases such as cystic fibrosis and alpha-1-antitrypsin deficiency. In addition, a wide range of conditions treatable via genetic immunization could benefit from this approach to gene delivery as well.


Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells.
Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.


Withdrawal from controlled carbamazepine therapy followed by further carbamazepine treatment in patients with dementia.
The aim of this study was to assess the effects of withdrawal from placebo and carbamazepine administered for agitation associated with dementia and to assess safety, tolerability, and efficacy of subsequent ongoing carbamazepine therapy. We previously reported the results of a 6-week, randomized, parallel-group study of placebo versus carbamazepine in 51 nursing home patients with dementia who were agitated; 47 subjects completed that study. This report first presents the results of withdrawal from that experimental treatment assessed by (blinded) observations 3 weeks later (N = 45 remaining). The primary outcome measure was the Brief Psychiatric Rating Scale. Secondary outcome measures addressed other aspects of behavior, cognition, function, safety, and tolerability. Patients were then treated with carbamazepine for an additional 6 weeks (N = 32 remaining) or 12 weeks (N = 25 remaining), with the same assessments performed. Patients who had previously shown behavioral improvement with carbamazepine therapy reverted to their baseline state after washout, whereas there was no change in the patients previously treated with placebo. There were no other significant effects of washout. During subsequent therapy with carbamazepine at a modal dose of 300 mg/day, there were 2 deaths and 4 other adverse events resulting in dropout. Neither of the deaths, and only 1 serious adverse experience, was judged to be related to carbamazepine. There were a variety of nonserious adverse experiences during the trial. Behavior ratings showed ongoing improvement in agitation and aggression, as well as in other aspects of psychopathology. The washout data provided independent confirmation of efficacy found in the prior placebo-controlled phase of this trial. Ongoing treatment was not associated with unexpected toxicity and was associated with improvement in measures of agitation and aggression that appeared to continue for up to 12 weeks. These findings confirm and extend results from earlier placebo-controlled studies.


Similarities and differences between eating disorders and obese patients in a virtual environment for normalizing eating patterns.
Virtual reality has demonstrated promising results in the treatment of eating disorders (ED); however, few studies have examined its usefulness in treating obesity. The aim of this study was to compare ED and obese patients on their reality judgment of a virtual environment (VE) designed to normalize their eating pattern. A second objective was to study which variables predicted the reality of the experience of eating a virtual forbidden-fattening food. ED patients, obese patients, and a non-clinical group (N=62) experienced a non-immersive VE, and then completed reality judgment and presence measures. All participants rated the VE with similar scores for quality, interaction, engagement, and ecological validity; however, ED patients obtained the highest scores on emotional involvement, attention, reality judgment/presence, and negative effects. The obese group gave the lowest scores to reality judgment/presence, satisfaction and sense of physical space, and they held an intermediate position in the attribution of reality to virtually eating a "fattening" food. The palatability of a virtual food was predicted by attention capturing and belonging to the obese group, while the attribution of reality to the virtual eating was predicted by engagement and belonging to the ED group. This study offers preliminary results about the differential impact on ED and obese patients of the exposure to virtual food, and about the need to implement a VE that can be useful as a virtual lab for studying eating behavior and treating obesity.


Neuroleptic dosage for Asians: a failure to replicate.
Retrospective chart review of 30 Asian patients and 30 matched Caucasian patients failed to replicate a previous report's finding that Asian patients require lower doses of neuroleptic medications than do Caucasian patients.


PDGFRalpha/beta expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategy.
As new multi-target tyrosine kinase inhibitors are emerging in the therapy of various malignancies, our aim was to define the co-expression pattern of receptor-tyrosine-kinase platelet-derived growth factor receptors alpha and beta (PDGFRalpha/beta) in human colorectal cancer. The co-expression pattern of PDGFRalpha/beta was analyzed by RT-PCR in 99 histologically confirmed human colorectal carcinomas and five colorectal cancer cell lines. In addition, immunohistochemical (IHC) staining was applied for confirmation of expression and analysis of receptor tyrosine kinase (RTK) localisation. The colorectal cancer cell lines that were analysed revealed varying expression intensities of PDGFRalpha and PDGFRbeta. The majority of human colorectal cancer specimens revealed a PDGFRalpha (83%) or PDGFRbeta (60%) expression. While PDGFRalpha showed a predominantly cytoplasmic staining in tumor cells as well as in stromal pericytes, PDGFRbeta was restricted to stromal pericytes only. Furthermore, PDGFRalpha expression significantly correlated with lymph node metastasis (P=0.0082) and advanced UICC stages III/IV (P=0.018) in older patients (P=0.043). PDGFRbeta expression only revealed a trend towards lymphatic dissemination (P=0.099). Co-expression of PDGFRalpha/beta occurred in 57% of the colorectal cancer samples, whereas another 29% of the samples depicted mono-expression of PDGFRalpha or PDGFRbeta. Notably, PDGFRalpha/beta expression significantly correlated with lymphatic metastasis (P=0.007) and advanced UICC stages III/IV (P=0.017) in older patients (P=0.03). In summary, our results revealed that PDGFRalpha/beta expression significantly correlates with lymphatic dissemination and therefore encourages application of PDGFRalpha/beta RTK-inhibitors within a combination therapy.


Studies on human thyroxine-binding globulin (TBG). IX. Some physical, chemical, and biological properties of radioiodinated TBG and partially desialylated TBG.
Thyroxine-binding globulin (TBG) and partially desialylated or slow TBG (STBG) were purified from human serum by affinity chromatography. Purified TBG was identical to TBG present in serum by the criteria of electrophoretic mobility, affinity for thyroxine (T4), and heat-inactivation response. Purified STBG had slower electrophoretic mobility and lower affinity for T4. Both bound T4 in an equimolar ratio, were immunoprecipitable, and had similar inactivation t1/2 at 61 degrees C. TBG and STBG were iodinated by the chloramine-T-catalyzed reaction. An average of from 0.02 to 6 atoms I could be incorporated per molecule of the protein by adjusting the conditions of the reaction (time, protein and iodide concentrations). 125-I, 131-I, and 127-I were used. Iodination increased the anodal mobility of TBG but did not affect the reversible T4-binding, precipitation by antiserum, or the heat-inactivation properties. "Heavily" and "lightly" iodinated TBG had identical disappearance half-times from serum in the rabbit. 15 min after the intravenous administration of [131-I]-STBG and [125-I]TBG mixture to rats, more than 90% of the injected 131-I dose was in the liver, and the liver 131-I/125-I ratio was 32-fold that of serum. Selective uptake of STBG by the liver was also observed in the rabbit and in man. The serum [125-I]STBG/[131-I]TBG ratio declined from 1 to 0.2 in 10 min in the intact rabbit but remained unchanged for 1 h in the acutely hepatectomized animal. In the rabbit, t 1/2 was approximately 3 min for STBG and 0.8-3.4 days for TBG. The radioiodine derived from the iodinated proteins is partly excreted in bile but the bulk was precipitable with specific antibodies. Some isotope in the form of iodide appeared in blood and was excreted in the urine. Since radioiodinated TBG and STBG preserve their biologic and immunologic properties they are useful as tracer materials for metabolic studies. In rat, rabbit, and man STBG is rapidly cleared from serum by the liver. Conversion of TBG to STBG may be the limiting step in the regulation of TBG metabolism.


Demethoxycurcumin-Loaded Chitosan Nanoparticle Downregulates DNA Repair Pathway to Improve Cisplatin-Induced Apoptosis in Non-Small Cell Lung Cancer.
Demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanoyl chitosan (CHC) nanomatrix has been successfully developed and used as a therapeutic approach to inhibit cisplatin-induced drug resistance by suppressing excision repair cross-complementary 1 (ERCC1) in non-small cell lung carcinoma cells (NSCLC). Previously, DMC significantly inhibited on-target cisplatin resistance protein, ERCC1, via PI3K-Akt-snail pathways in NSCLC. However, low water solubility and bioavailability of DMC causes systemic elimination and prevents its clinical application. To increase its bioavailability and targeting capacity toward cancer cells, a DMC-polyvinylpyrrolidone core phase was prepared, followed by encapsulating in a CHC shell to form a DMC-loaded core-shell hydrogel nanoparticles (DMC-CHC NPs). We aimed to understand whether DMC-CHC NPs efficiently potentiate cisplatin-induced apoptosis through downregulation of ERCC1 in NSCLC. DMC-CHC NPs displayed good cellular uptake efficiency. Dissolved in water, DMC-CHC NPs showed comparable cytotoxic potency with free DMC (dissolved in DMSO). A sulforhodamine B (SRB) assay indicated that DMC-CHC NPs significantly increased cisplatin-induced cytotoxicity by highly efficient intracellular delivery of the encapsulated DMC. A combination of DMC-CHC NPs and cisplatin significantly inhibited on-target cisplatin resistance protein, ERCC1, via the PI3K-Akt pathway. Also, this combination treatment markedly increased the post-target cisplatin resistance pathway including bax, and cytochrome c expressions. Thymidine phosphorylase (TP), a main role of the pyrimidine salvage pathway, was also highly inhibited by the combination treatment. The results suggested that enhancement of the cytotoxicity to cisplatin via administration of DMC-CHC NPs was mediated by down-regulation of the expression of TP, and ERCC1, regulated via the PI3K-Akt pathway.


Working-class Filipino women's perspectives on factors that facilitate or hinder prenatal micronutrients supplementation to prevent congenital anomalies.
The study was conducted to plan for a community-health campaign to inform working-class Filipinos about the causes and prevention of orofacial clefting. Prenatal micronutrients may play a role in preventing orofacial clefting. Therefore, women's practices and perspectives on barriers to and facilitators of micronutrient supplementation were elicited. A total of 43 women and 22 health care workers were interviewed. Barriers to taking supplements included side effects, late prenatal care, the view that micronutrients are medications, inadequate supply, and health care workers who were unaware that prenatal vitamin supplements prevent congenital anomalies. The main facilitator was women's understanding that prenatal micronutrients improve the physical well-being of both mother and child. Given that women view having healthy babies as a reason to take micronutrients and that the health care workers lacked knowledge related to the use of micronutrients to prevent congenital anomalies, uptake of prenatal micronutrient supplementation programs may improve by specifically promoting the health benefit of preventing congenital anomalies.


Cefoperazone-sulbactam for treatment of intra-abdominal infections: results from a randomized, parallel group study in India.
Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option. This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India. Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%). Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.


Scope and Standards: Defining the Advanced Practice Role in Genetics.
Because knowledge concerning genetics and genomics and its application to oncology care is continuing to grow, oncology nurses must be aware of appropriate advanced scope of practice roles based on education and training. All nurses must develop and maintain knowledge of the field, but advanced practice nurses working in genetics have additional competencies and management expectations. Collaboration among practice levels and disciplines is essential. This article focuses on the advanced practice role as further defined in published resources outlining scope of practice in genetics. .


Assessing environmental health impacts of coal mining exploitation in Iran: A Rapid Impact Assessment Matrix (RIAM) approach for environmental protection.
Environmental Impact Assessment is the process of evaluating the effects caused by a project on the environment. The outcomes generated by this assessment can lead to a reduction of the negative effects and an increase in the positive effects caused by mine projects. The present study was conducted to evaluate the environmental impact assessment of the Goliran Coal Mine in northern Iran. In the descriptive-analytical study, to achieve the objectives, observatory surveys were conducted around the coal mine using a checklist, which was about the positive and negative effects of a coal mine. Then the data were entered into the RIAM and the positive and negative effects were ranked and the most important effects were determined. In RIAM, one point is assigned to each component. 17 important activities for environmental impacts were identified using a checklist. Among the activities carried out at the coal mine site, the major ones included tunnel excavation, construction of the rail line collection and disposal of coal mine effluent, coal transportation, collection and disposal of mine tailings, and technical defects and leakage. The scores of each environmental factor were based on the four environmental components: physical/chemical, biological/ecological, social/cultural, and economic/operational. The results of the present study showed that the most negatively affected environmental components are the physical/chemical components derived from three activities; the construction of the underground tunnel; the construction of a coal transport rail line; and the actual transportation of coal extracts. The scores of each environmental factor based on the four components at the Goliran coal mine in northern Iran indicate that the highest negative score was -64, corresponding to the physical/chemical component, and was assigned to air pollution. On the other hand, the highest positive score corresponds to the economic/operational component with +54, assigned to the income that employees earn from the mine. Overall results showed that the coal mine in northern Iran had negative effects on the environment but the effects were not severe. It is suggested that for future research, corrective measures should be taken in the form of an environmental management plan to reduce the negative effects caused by coal mining, and then prospective research should be done to check the extent of reducing the negative effects.


The S. pombe zfs1 gene is required to prevent septation if mitotic progression is inhibited.
Schizosaccharomyces pombe cdc16p is required to limit the cell to forming a single division septum per cell cycle; the heat-sensitive loss-of-function mutant cdc16-116 completes mitosis, and then undergoes multiple rounds of septum formation without cell cleavage. cdc16p is a homologue of Saccharomyces cerevisiae BUB2p, and has also been implicated in the spindle assembly checkpoint function in S. pombe. To identify other proteins involved in regulating septum formation, we have screened for multicopy suppressors of the cdc16-116 mutation. In this paper, we describe one of these suppressors, zfs1. The null allele (zfs1-D1) is viable. However, at low temperatures it divides at a reduced size, while at higher temperatures, it partially suppresses heat sensitive mutants in genes signalling the onset of septum formation. Zfs1-D1 cells show an increased rate of chromosome loss during exponential growth. Moreover, if assembly of the spindle is prevented, zfs1-D1 cells do not arrest normally, but the activity of cdc2p kinase decays, and cells form a division septum without completing a normal mitosis. We conclude that zfs1 function is required to prevent septum formation and exit from mitosis if the mitotic spindle is not assembled. The suppression of cdc16-116 by zfs1 is independent of dma1 function and the spindle assembly checkpoint genes mad2 and mph1. The genetic interactions of zfs1 with genes regulating septum formation suggest that it may be a modulator of the signal transduction network controlling the onset of septum formation and exit from mitosis.


Cell wall and DNA cosegregation in Bacillus subtilis studied by electron microscope autoradiography.
Cells of a Bacillus subtilis mutant deficient in both major autolytic enzyme activities were continuously labeled in either cell wall or DNA or both cell wall and DNA. After appropriate periods of chase in minimal as well as in rich medium, thin sections of cells were autoradiographed and examined by electron microscopy. The resolution of the method was adequate to distinguish labeled DNA units from cell wall units. The latter, which could be easily identified, were shown to segregate symmetrically, suggesting a zonal mode of new wall insertion. DNA units could also be clearly recognized despite a limited fragmentation; they segregated asymmetrically with respect to the nearest septum. Analysis of cells simultaneously labeled in cell wall and DNA provided clear visual evidence of their regular but asymmetrical cosegregation, confirming a previous report obtained by light microscope autoradiography (J.-M. Schlaeppi and D. Karamata, J. Bacteriol. 152:1231-1240, 1982). In addition to labeled wall units, electron microscopy of thin sections of aligned cells has revealed fibrillar networks of wall material which are frequently associated with the cell surface. Most likely, these structures correspond to wall sloughed off by the turnover mechanism but not yet degraded to filterable or acid-soluble components.


Getting the Opportunity to Fly on your own.
The author describes the beginning of her independent scientific career in the Department of Biochemistry of the University of Geneva, at a time when Assistant Professor positions did not exist there and female group leaders in the Section of Chemistry were a rare species. Good timing, strong support and an excellent atmosphere are what she remembers. Her stay there was absolutely crucial to her success.


[The effect of glucose and cycloheximide on glycerolipid biosynthesis in the rat liver].
Glucose and cycloheximide activated biosynthesis of phospholipids and, especially, of triacylglycerols involving 14C-acetate in rat liver tissue in vivo. Starvation did not affect the glycerolipid biosynthesis but decreased markedly the cholesterol production. In liver tissue of starved rats cycloheximide activated synthesis of glycerolipids and inhibited the cholesterol synthesis. Administration of glucose into the animals under conditions of their satiation augmented the fatty acid synthesis; the activating effect of cycloheximide was more distinct as compared with glucose. In satiated animals the most part of the label was incorporated into glycerolipid fatty acids after glucose and cycloheximide administration. Starvation inhibited synthesis of fatty acids with simultaneous activation of the glycerolipid glycerol production; cycloheximide activated still further the glyceroneogenesis. Both glucose and cycloheximide activated biosynthesis of palmitic and oleic acids of glycerolipids and inhibited the arachidonic acid synthesis. Similarity in the effect of glucose and cycloheximide on the glycerolipid biosynthesis might occur due to stimulation of glyceroneogenesis and to augmented production of alpha-glycerophosphate, which in turn increased the fatty acid esterification.


[Evaluation of alternations in mental performance due to the effect of extended isolation].
Dynamics of mental performance, critical periods of adaptation, and cognitive processes were studies in conjunction with extended experimental isolation. Training to simple motor skills was found to be less impeded by prolonged isolation as opposed to operations requiring active involvement of higher psychic functions (memory, concentration, thinking). Experiments HUBES and ECOPSY strengthened the hypothesis concerning possible advent of critical periods in prolonged isolation impacting mental performance. They are the initial period (week 1 in isolation), emergency, arrival of visiting crews, and finishing two weeks. Effect of isolation was not so much evident from changes in absolute meanings of work parameters as from the reduction of their stability in time.


Immunolocalization of beta catenin in intestinal polyps of Peutz-Jeghers and juvenile polyposis syndromes.
To examine the membranous and nuclear distribution of beta catenin in the epithelial cells of gut polyps from Peutz-Jeghers syndrome and juvenile polyposis in comparison with other types of polyps and tumours. Immunohistochemistry for beta catenin and proliferation markers was performed on conventional paraffin sections. Immunohistological staining was carried out on Peutz-Jeghers syndrome polyps from four different families, on juvenile polyposis polyps from two different families, on solitary juvenile polyps, and on hyperplastic polyps. The immunohistochemistry was evaluated qualitatively in relation to defined areas of the polyps. All polyps from the hamartomatous polyposis syndromes (Peutz-Jeghers syndrome and juvenile polyposis) showed nuclear localization of beta catenin in some epithelial cell nuclei. In Peutz-Jeghers syndrome polyps beta catenin positive nuclei were seen at the base of the deep crypt infoldings. In juvenile polyposis polyps and in some solitary juvenile polyps they were found in irregularly distributed cryptal epithelial cells corresponding to the proliferative compartments. Normal mucosa of the gut and hyperplastic polyps of the colon do not show nuclear staining for beta catenin. The dysregulation of cellular beta catenin distribution is not only a phenomenon of adenoma formation and adenoma progression in the colon--it is at least focally present in polyps of the hamartomatous type and is related to the proliferation zones of these polyps. The nuclear translocation of beta catenin most probably reflects a disturbed beta catenin metabolism. In view of the different functions of beta catenin during development and cell differentiation, the nuclear translocation of beta catenin is likely to be an important factor in enhanced cell proliferation which escapes local control mechanisms.