Localization of pancreatic inflammation and necrosis in dogs.
Few studies of the prevalence of histologic lesions of the exocrine pancreas in dogs have been reported, and none of them systematically evaluate the localization of these lesions. The purpose of this study was to describe the anatomic localization of pancreatic inflammation, necrosis, and fibrosis in dogs presented for postmortem examination. Seventy-three pancreata from dogs presented for postmortem examination were evaluated and investigated for the presence of suppurative inflammation (SI), pancreatic necrosis (PN), and lymphocytic inflammation (LI). Sections that showed evidence of SI, PN, or LI also were evaluated for pancreatic fibrosis (F). The tendency for a preferred localization for SI, PN, and LI was evaluated by chi-square analysis. A total of 47 pancreata with histologic evidence of pancreatitis (SI, PN, or LI; F alone was not considered evidence of pancreatitis) were identified. Twenty-four (51.1%) had SI, 23 (48.9%) had PN, and 34 (72.3%) had LI. Of the 47 dogs with SI, PN, or LI, 28 (59.6%) had F. The distribution of SI, PN, and LI between the right and the left limb of the pancreas and among the 5 anatomic regions was random, based on a goodness-of-fit test. We conclude that pancreatic inflammation tends to occur in discrete areas within the pancreas rather than diffusely throughout the whole organ. These findings suggest that a single biopsy is insufficient to exclude subclinical pancreatitis and that there is no preferred site for pancreatic biopsy collection unless gross lesions are apparent.


Effects of risperidone, quetiapine and ziprasidone on ethanol withdrawal syndrome in rats.
Comorbid substance use in schizophrenic patients is common, and substance dependence is a predictive factor for psychosis. The present study was designed to investigate the effects of risperidone, quetiapine and ziprasidone, atypical antipsychotic drugs, on ethanol withdrawal syndrome (EWS) in rats. Adult male Wistar rats were used in the study. Ethanol (7.2%, v/v) was given to rats via a liquid diet for 21 days. An isocaloric liquid diet without ethanol was given to control rats. Risperidone (1 and 2 mg/kg), quetiapine (8 and 16 mg/kg), ziprasidone (0.5 and 1 mg/kg) and vehicle were injected into rats intraperitoneally at 1.5 and 5.5 h of ethanol withdrawal. At the 2nd, 4th and 6th hours of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, stereotyped behaviors, abnormal gait and posture, tail stiffness and agitation were recorded or rated. Following the observations at the 6th hour, the rats were tested for audiogenic seizures. All three drugs had some significant inhibitory effects on EWS-induced behavioral signs beginning at the 2nd hour of withdrawal. The drugs also significantly reduced the incidence of audiogenic seizures. Overall, risperidone and quetiapine seemed to be more effective than ziprasidone in ameliorating the withdrawal signs. Doses of the drugs used in the present study did not produce any significant changes in locomotor activities of naïve rats. Our results suggest that risperidone, quetiapine and ziprasidone had beneficial effects on EWS in rats. Thus, these drugs may be helpful for controlling withdrawal signs in ethanol-dependent patients.


Device-based physical activity levels among Finnish adolescents with functional limitations.
Monitoring physical activity among young adolescents with disabilities is a top academic priority. People with disabilities are a diverse group with various abilities in different human functioning. Therefore, we used a novel approach through functional limitations as a marker for disabilities and examined physical activity levels. To investigate the levels and differences in light (LPA) and moderate-to-vigorous (MVPA) intensity physical activity between young adolescents with and without functional limitations. The study included young adolescents (n = 1436) aged 11-15 years olds who attended general schools that were part of the 2016 Finnish School-aged Physical Activity (FSPA) study. PA levels were measured by hip-worn accelerometers during seven consecutive days. The data were disaggregated by the following functions related to; seeing, hearing, speaking, moving, breathing, and remembering or concentrating. Multiple general linear regression models were run to test the differences in amount of time of LPA and MVPA. One in six young adolescents had disabilities. Young adolescents with functional limitations had 7 min.day-1 less LPA (p = 0.021) and 8 min.day-1 less MVPA (p = 0.011) than their peers without functional limitations. After controlling for gender, age, and device wear time, the differences in LPA among young adolescents with and without functional limitations were the same, however MVPA was no longer significantly less. Results varied according to different functional limitations. There were significant variations in physical activity behaviours by functional limitations and activity intensity. As such, tailored approaches to physical activity promotion may be dependent on understanding functional limitations as an indicator to disabilities.


Regression of cancer following surgery.
Postsurgical tumor regressions are rare but well-recognized entities. The causes of such phenomena are unknown but probably are multiple. Regression of any tumor must ultimately come about by changes in the host-tumor interaction which suddenly becomes unfavorable for tumor growth. This is likely a manifestation of changes in the immunocompetence of the host. There are many variables influencing the host-tumor interaction, and the study of tumor immunology is stil in its infancy. It is through the exploration and investigation of basic mechanisms of the immunology of cancer that the most potentially fruitful associations between tumor growth or regression and surgical manipulations may be made and applied to the treatment of cancer patients.


Role of patient characteristics for fast-track hip and knee arthroplasty.
Patient age and comorbidity have been found to increase the length of hospital stay (LOS), readmissions, and mortality after surgery, including in elective primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Whether the same applies in fast-track THA and TKA with early mobilization and an LOS aim of 2-4 days remains unanswered. A prospective study on patient characteristics and comorbidity in consecutive unselected patients undergoing fast-track THA and TKA was cross-referenced with the Danish National Health Registry and medical charts allowing complete 90 days follow-up. A total of 3112 THA/TKAs were performed in 3020 patients. The mean age was 67 (range 18-97) years. The median LOS was 3 (inter-quartile range: 1) and the mean 3.0 days (range 1-34), with 91% having LOS ≤4 days. Age 76-80 [odds ratio (OR): 1.57; 95% confidence interval (CI): 0.99-2.47], 81-85 (OR: 2.40; 1.45-4.00), and >85 yr (OR: 4.10; 2.15-7.82), preoperative cardiopulmonary disease (CPD) (OR: 1.40; 1.03-1.91), preoperative use of a mobility aid (OR: 1.95; 1.46-2.54), and living conditions (OR: 1.92; 1.44-2.54) were related to LOS >4 days. However, more than 75% of those aged over 80 yr or with these conditions had an LOS ≤4 days. Mortality and readmission rate were 0.22% and 6.6%, respectively, at 30 days and 0.42% and 9.3% at 90 days. Readmissions were similarly related to older age, CPD, and use of mobility aids. Fast-track THA and TKA with LOS of ≤4 days and discharge to home is feasible and safe, including in elderly patients with comorbidities.


Simultaneous acral nodular eruption and flagellate erythema caused by bleomycin.
A 29-year-old male with AIDS was treated with bleomycin and vincristine for visceral Kaposi's sarcoma. Three days later, he developed two distinct eruptions simultaneously. One eruption was characterized by tender, erythematous, edematous plaques and nodules on the palmar and dorsal surfaces of the hands, forearms, and elbows. The other consisted of grouped, erythematous, hyperpigmented streaks on the trunk, buttocks, and extremities. The patient subsequently received a second treatment consisting of vincristine with adriamycin, without bleomycin, and no cutaneous effects were seen. Diagnoses of flagellate erythema and acral nodular eruption secondary to bleomycin were made and confirmed histopathologically. To our knowledge, this is the first report of two cutaneous side effects of bleomycin appearing simultaneously in a patient with AIDS.


Gastrointestinal bleeding. Radiological diagnosis.
Gastrointestinal haemorrhage is a common clinical problem that often presents the clinician with difficulties in diagnosis. The increasingly important role of endoscopy has resulted in a change of emphasis in the radiological investigation of bleeding: while barium studies are still an important part of the investigative sequence in most patients they no longer occupy the central position in diagnosis they once held, despite considerable improvements in technique. At the same time angiography and interventional radiological techniques are becoming progressively more important in the diagnosis and management of gastrointestinal bleeding. In acute gastrointestinal haemorrhage angiography provides not only one of the most accurate techniques for the localization of bleeding (Boijsen and Reuter, 1967) but also the therapeutic option of embolization. In chronic gastrointestinal bleeding of obscure origin angiography may be the only modality of investigation that can successfully locate a microvascular abnormality. In the assessment of portal hypertension angiographic and interventional techniques may provide both physician and surgeon with information vital to the successful management of the patient.


Exploring the natural fungal biodiversity of tropical and temperate forests toward improvement of biomass conversion.
In this study, natural fungal diversity in wood-decaying species was explored for biomass deconstruction. In 2007 and 2008, fungal isolates were collected in temperate forests mainly from metropolitan France and in tropical forests mainly from French Guiana. We recovered and identified 74 monomorph cultures using morphological and molecular identification tools. Following production of fungal secretomes under inductive conditions, we evaluated the capacity of these fungal strains to potentiate a commercial Trichoderma reesei cellulase cocktail for the release of soluble sugars from biomass. The secretome of 19 isolates led to an improvement in biomass conversion of at least 23%. Of the isolates, the Trametes gibbosa BRFM 952 (Banque de Ressources Fongiques de Marseille) secretome performed best, with 60% improved conversion, a feature that was not universal to the Trametes and related genera. Enzymatic characterization of the T. gibbosa BRFM 952 secretome revealed an unexpected high activity on crystalline cellulose, higher than that of the T. reesei cellulase cocktail. This report highlights the interest in a systematic high-throughput assessment of collected fungal biodiversity to improve the enzymatic conversion of lignocellulosic biomass. It enabled the unbiased identification of new fungal strains issued from biodiversity with high biotechnological potential.


Psychological distress, depression, anxiety, and life satisfaction following COVID-19 infection: evidence from 11 UK longitudinal population studies.
Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (-0·06 [-0·08 to -0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4-12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. UK Medical Research Council and UK National Institute for Health and Care Research.


Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.
Crohn's disease (CD) is a presentation of inflammatory bowel disease (IBD) that manifests in childhood and adolescence and involves chronic and severe enterocolitis, immune and gut microbial dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories that could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (wt/wt) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation with Helicobacter hepaticus, which triggers Crohn's-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, for example, Escherichia coli and Helicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research.IMPORTANCETo our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn's disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.


Role of hypoxia and epithelial-mesenchymal transition in the formation and maintenance of oral cancer stem cells in oral squamous cell carcinomas and metastatic lymph node: An immunohistochemical analysis.
Inspite of having advanced treatment modalities the overall survival rate in oral squamous cell carcinoma (OSCC) remains poor. This is considered to be mainly due to local recurrence and distant metastasis. Various studies have concentrated on the role of oral cancer stem cells (OCSCs) in the progression and metastasis of OSCC. However, the role of tumor microenvironment components has been less delved into. Hence clarity on cell biology and metastatic potential OCSCs is essential for the development of more effective anti-cancer treatment. To establish the role of OCSCs in different grades of OSCC and metastatic lymph nodes through the expression of cluster of differentiation 44 (CD44). To demonstrate and correlate the role of hypoxia and Epithelial mesenchymal transition (EMT) in the various grades and metastatic lymph nodes in the formation and maintenance of OCSCs by employing Hypoxia-inducible factor-1 Alpha (HIF 1α) and Snail respectively. A total of 36 cases of OSCC, 12 from each grade and 12 normal oral mucosal tissues were included in the study. Immunohistochemical staining was performed for the demonstration of CD44, HIF1α, and Snail. Descriptive analysis, Chi-square, and Spearman's rank correlation were used to analyze frequency and proportion, to compare expression and correlate between lesion proper and lymph node in each group respectively. Significant expression of CD44, HIF1 α, and Snail among advancing grades of OSCC and their metastatic lymph node were observed. A positive correlation was seen between them. The prognosis of OSCC can be improved by better understanding and targeting the molecules involved in the formation and maintenance of OCSCs.


Ivabradine on aortic stiffness in patients with heart failure.
The aim of this study was to evaluate the effect of ivabradine treatment on aortic stiffness by measuring aortic elastic parameters in patients with heart failure (HF) receiving ivabradine treatment. The study included clinical patients who were diagnosed with HF (ejection fraction, <35%), had sinus rhythm and persistent symptoms despite full medical treatment. The study group consisted of patients with a heart rate greater than 70 beats per minute and the control group consisted of patients with a heart rate less than 70 beats per minute. Echocardiographic measurements were conducted and aortic strain, aortic distensibility, and aortic stiffness index were calculated. By the end of the twelfth month, a decrease was observed in the left ventricular end-diastolic and end-systolic volumes, whereas ejection fraction was increased (P < 0.001). When aortic elastic parameters were evaluated between the 2 groups, there was no significant difference regarding aortic strain, aortic distensibility, and aortic stiffness index at the time of enrollment and during the visit at 3 months. At the twelfth month visit, aortic strain (P < 0.001) and distensibility (P < 0.001) were significantly increased, whereas there was a significant decrease in the aortic stiffness index (P < 0.001). During the follow-up at 12 months, significant improvements were observed in the left ventricular functions and aortic elastic parameters along with decreased heart rate in patients with HF receiving ivabradine treatment. This outcome may indicate that ivabradine treatment may correct aortic stiffness and may reduce aortic stiffness after 1 year of follow-up.


Involvement of chemokine receptor 4/stromal cell-derived factor 1 system during osteosarcoma tumor progression.
Despite intensive chemotherapy and surgery treatment, lung and bone metastasis develop in about 30% of patients with osteosarcoma. Mechanisms for this preferential metastatic behavior are largely unknown. We investigated the role of the chemokine receptor 4 (CXCR4)/stromal cell-derived factor 1 (SDF-1) system to drive the homing of osteosarcoma cells. We analyzed the expression of the CXCR4 and SDF-1 proteins on several osteosarcoma cell lines and the effects of SDF-1 on migration, adhesion, and proliferation of these cancer cells. In vitro assays showed that the migration of osteosarcoma cells expressing CXCR4 receptor follows an SDF-1 gradient and that their adhesion to endothelial and bone marrow stromal cells is promoted by SDF-1 treatment. Moreover, the production of matrix metalloproteinase-9 is increased after SDF-1 exposure. We finally proved in a mouse model our hypothesis of the CXCR4/SDF-1 axis involvement in the metastatic process of osteosarcoma cells. Development of lung metastasis after injection of osteosarcoma cells was prevented by the administration of a CXCR4 inhibitor, the T134 peptide. These data show a possible explanation for the preferential osteosarcoma metastatic development into the lung, where SDF-1 concentration is high, and suggest that molecular strategies aimed at inhibiting the CXCR4/SDF-1 pathway, such as small-molecule inhibitors or anti-CXCR4 antibodies, might prevent the dissemination of osteosarcoma cells.


Secreted products of a nonmucoid Pseudomonas aeruginosa strain induce two modes of macrophage killing: external-ATP-dependent, P2Z-receptor-mediated necrosis and ATP-independent, caspase-mediated apoptosis.
A nonmucoid clinical isolate of Pseudomonas aeruginosa, strain 808, elaborated ATP-dependent and ATP-independent types of cytotoxic factors in the growth medium. These cytotoxic factors, active against macrophages, were secreted during the exponential phase of growth in a complex medium. Commensurate with the appearance of the cytotoxic activities in the cell-free growth medium, several ATP-utilizing enzymic activities, such as adenylate kinase, nucleoside diphosphate kinase and 5'-nucleotidase (ATPase and/or phosphatase), were detected in the medium. These ATP-utilizing enzymes are believed to convert external ATP, presumably effluxed from macrophages, to various adenine nucleotides, which then activate purinergic receptors such as P2Z, leading to enhanced macrophage cell death. Pretreatment of macrophages with periodate-oxidized ATP (oATP), which is an irreversible inhibitor of P2Z receptor activation, prevented subsequent ATP-induced macrophage cell death. A second type of cytotoxic factor(s) operated in an ATP-independent manner such that it triggered activation of apoptotic processes in macrophages, leading to proteolytic conversion of procaspase-3 to active caspase-3. This cytotoxic factor(s) did not appear to act on procaspase-3 present in macrophage cytosolic extracts. Intact macrophages, when exposed to the cytotoxic factor(s) for 6-16 h, underwent apoptosis and demonstrated the presence of active caspase-3 in their cytosolic extracts. Interestingly, two redox proteins, azurin and cytochrome c(551), were detected in the cytotoxic preparation. When cell-line-derived or peritoneal macrophages or mast cells were incubated overnight with Q-Sepharose column flow-through fraction or with a mixture of azurin and cytochrome c(551), they underwent extensive cell death due to induction of apoptosis.


A comparison of clinician, youth, and parent beliefs about helpfulness of interventions for early psychosis.
This study explored whether there are gaps between the beliefs of clinicians and those of young people and their parents about the appropriate interventions for early psychosis. Postal surveys of 105 Australian general practitioners, 155 psychiatrists, 183 psychologists, and 106 mental health nurses asked about the likely helpfulness of a wide range of potential interventions, covering helping professions, medications, psychological interventions, complementary interventions, and self-help. The results from these clinicians were compared with data from a national telephone survey of 968 Australian youths (ages 12-25 years) and 531 of their parents. Young people and their parents were less likely than the clinicians to endorse the helpfulness of seeing a psychiatrist, using mental health services, and taking antipsychotic medication. On the other hand, young people and their parents were more likely to endorse informal social supports, generic counseling, and general stress reduction methods. The gap in intervention beliefs may be a contributor to delays in seeking professional help and adherence to treatment. Efforts are needed to improve public knowledge about psychosis treatment and to change mental health services so that they better meet consumer expectations.


Evaluation of bioaerosol samplers for the detection and quantification of influenza virus from artificial aerosols and influenza virus-infected ferrets.
Bioaerosol sampling devices are necessary for the characterization of infectious bioaerosols emitted by naturally-infected hosts with acute respiratory virus infections. Assessment of these devices under multiple experimental conditions will provide insight for device use. The primary objective of this study was to assess and compare bioaerosol sampling devices using a) an in vitro, environmentally-controlled artificial bioaerosol system at a range of different RH conditions and b) an in vivo bioaerosol system of influenza virus-infected ferrets under controlled environmental conditions. Secondarily, we also sought to examine the impact of NSAIDs on bioaerosol emission in influenza virus-infected ferrets to address its potential as a determinant of bioaerosol emission. We examined the performance of low and moderate volume bioaerosol samplers for the collection of viral RNA and infectious influenza virus in vitroand in vivo using artificial bioaerosols and the ferret model of influenza virus infection. The following samplers were tested: the polytetrafluoroethylene filter (PTFE filter), the 2-stage National Institute of Occupational Safety and Health cyclone sampler (NIOSH cyclone sampler) and the 6-stage viable Andersen impactor (Andersen impactor). The PTFE filter and NIOSH cyclone sampler collected similar amounts of viral RNA and infectious virus from artificially-generated aerosols under a range of relative humidities (RH). Using the ferret model, the PTFE filter, NIOSH cyclone sampler and the Andersen impactor collected up to 3.66 log10 copies of RNA/L air, 3.84 log10 copies of RNA/L air and 6.09 log10 copies of RNA/L air respectively at peak recovery. Infectious virus was recovered from the PTFE filter and NIOSH cyclone samplers on the peak day of viral RNA recovery. The PTFE filter and NIOSH cyclone sampler are useful for influenza virus RNA and infectious virus collection and may be considered for clinical and environmental settings.


Understanding Approaches to the Dorsal Hump.
Dorsal hump reduction is a central component of western aesthetic rhinoplasty. Surgical success begins with knowledge of aesthetic ideals and accurate preoperative analysis. Knowledge of the patient's distortion from aesthetic ideals informs approach, technique, and instrument selection. Both endonasal and external approaches are suitable for dorsal hump reduction, though the latter affords more versatility when other surgical modifications are necessary. The main techniques consist of en bloc, Skoog, and component resection. Each has their distinct advantage, though a surgeon's comfort level with each should impact technique selection. Completion of the dorsal reduction often leaves a defect that must be reconstructed. Failure to anticipate the potential long-term sequelae and appropriately manage the dorsal defect can lead to a poor result and patient dissatisfaction.


[Histopathological differential diagnosis in inflammatory bowel diseases].
In front of the suspicious diagnosis of an inflammatory bowel disease (IBD), the pathologist must have adequate and complete clinical, anamnestic, instrumental informations and, if possible, the previous histopathologic examinations. This is necessary because: the diagnosis of IBD is made with exclusion criteria, different pathologic entities may have similar macroscopic and microscopic findings and the characteristic lesions are often present in little number. The authors consider in this paper the problem of the differential diagnosis of IBD.


A precise and adaptive neural mechanism for predictive temporal processing in the frontal cortex.
The theory of predictive processing posits that the brain computes expectations to process information predictively. Empirical evidence in support of this theory, however, is scarce and largely limited to sensory areas. Here, we report a precise and adaptive mechanism in the frontal cortex of non-human primates consistent with predictive processing of temporal events. We found that the speed of neural dynamics is precisely adjusted according to the average time of an expected stimulus. This speed adjustment, in turn, enables neurons to encode stimuli in terms of deviations from expectation. This lawful relationship was evident across multiple experiments and held true during learning: when temporal statistics underwent covert changes, neural responses underwent predictable changes that reflected the new mean. Together, these results highlight a precise mathematical relationship between temporal statistics in the environment and neural activity in the frontal cortex that may serve as a mechanism for predictive temporal processing.


Substance use and social stability of homeless youth: A comparison of three interventions.
The current study identified subgroups of homeless youth and young adults that exhibited distinct co-occurring patterns of substance use and social stability (e.g., employment, school attendance, and housing), and evaluated the relative effectiveness of the Community Reinforcement Approach (CRA), Motivational Enhancement Therapy (MET), and case management (CM) in interrupting substance use and improving social stability. The differentiating effects of personal characteristics on the co-occurrence of substance use and social stability were also examined. Participants included 270 homeless youth and young adults who were randomly assigned to one of the three intervention conditions: CRA, n = 93, MET, n = 86, or CM, n = 91. Participants were assessed at baseline, 3, 6, and 12 months postbaseline. A dual trajectory latent class growth analysis identified four co-occurring patterns: low-stable substance use paired with low-increasing social stability, high-stable substance use paired with low-stable social stability, high-declining substance use paired with low-increasing social stability, and low-increasing substance use paired with high-stable social stability. Findings showed that CRA was superior in improving substance use and social stability simultaneously compared to MET and CM, and further, CM was more effective than MET. Personal factors including race, age, coping strategies, and behavior problems differentiated the co-occurring patterns of substance use and social stability. The findings underscore the significance in identifying subgroups of homeless youth that vary in problem severity in terms of their substance use and social stability, and offer evidence to help practitioners identify the most effective intervention that responds to the needs of homeless youth. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Use of preexisting radiographs for assessing periodontal disease in epidemiologic studies.
This study evaluates the feasibility of obtaining preexisting dental radiographs by mail, the validity of assessing alveolar bone loss from posterior radiographs compared to full mouth, and the validity of alveolar bone loss assessed from radiographs taken at different times. This investigation uses data obtained for a study evaluating associations between oral conditions, blood biomarkers, and coronary heart disease within two large cohorts: the Nurses' Health Study and the Health Professionals Follow-up Study. If consenting participants had dental radiographs, we requested these radiographs from their dentists. Some dentists returned multiple sets of radiographs, which enabled us to conduct this study. A calibrated periodontist read all radiographs with good intraexaminer reliability (r=0.91). We compared posterior radiographs to full mouth (n=121 sets), as well as radiographs taken at different times (mean difference of 5 years) (n=102 pairs). Of the 812 participants, 81 percent consented and 66 percent provided radiographs. Posterior radiographs underestimated periodontitis (> or =1 site with > or =5 mm alveolar bone loss) prevalence by 6 percent (53.7% vs 57.0%) compared to full mouth, with sensitivity of 0.94 (95% confidence interval [CI]=0.86, 0.98) and specificity of 1. Spearman correlation coefficients comparing mean alveolar bone loss were 0.70 for anterior versus posterior teeth (mean difference=0.48), 0.92 for posterior teeth versus full mouth (mean difference=0.25), and 0.78 for pairs of radiographs taken at different times (mean difference=0.01). The kappa statistic was 0.70 comparing radiographs taken within 5 years and 0.29 when the period extended beyond 5 years. Preexisting radiographs are feasible for use in epidemiologic studies and provide valid assessments of periodontal disease.


Peak Cardiorespiratory Responses of Patients with Subacute Stroke During Land and Aquatic Treadmill Exercise.
The aim of this work was to investigate the cardiorespiratory responses of patients with subacute stroke to exercise stress tests with aquatic and land treadmills. Twenty-one consecutive patients who presented with first-ever subacute stroke in 2013-2015. All subjects underwent symptom-limited incremental exercise testing with aquatic and land treadmills. Land treadmill speed started at 1.5 km/h and increased 0.5 km/h every 1 to 2 minutes until maximal tolerable speed was achieved. Thereafter, the grade was elevated by 2% every 2 minutes. In the aquatic treadmill test, subjects were submerged to the xiphoid in 28°C water. Treadmill speed started at 1.5 km/h and was increased 0.5 km/h every 2 minutes thereafter. Cardiorespiratory responses were recorded with aquatic and land treadmills. Compared to land treadmill exercise, aquatic treadmill exercise achieved significantly better peak VO2 (22.0 vs 20.0; P = 0.02), peak metabolic equivalents (6.3 vs 5.8; P = 0.02), and peak rating of perceived exertion (17.6 vs 18.4, P = 0.01). Heart rate and VO2 correlated significantly during both tests (land treadmill: r = 0.96, P < 0.001; aquatic treadmill: r = 0.99, P < 0.001). Aquatic treadmill exercise elicited significantly better peak cardiorespiratory responses than land treadmill exercise and may be as effective for early intensive aerobic training in subacute stroke patients.


How Best to Implement Climate-smart Actions in Clinical Urologic Care.
We highlight the need for multidisciplinary teamwork, education, practical sustainability actions, informed choices for devices, and research in urologic care to reduce its environmental impact while maintaining quality health care for patients.


Age at Autism Spectrum Disorder (ASD) Diagnosis by Race, Ethnicity, and Primary Household Language Among Children with Special Health Care Needs, United States, 2009-2010.
We examined prevalence of diagnosed autism spectrum disorder (ASD) and age at diagnosis according to child's race/ethnicity and primary household language. From the 2009-2010 National Survey of Children with Special Health Care Needs, we identified 2729 3-17-year-old US children whose parent reported a current ASD diagnosis. We compared ASD prevalence, mean diagnosis age, and percentage with later diagnoses (≥5 years) across racial/ethnic/primary household language groups: non-Hispanic-white, any language (NHW); non-Hispanic-black, any language (NHB); Hispanic-any-race, English (Hispanic-English); and Hispanic-any-race, other language (Hispanic-Other). We assessed findings by parent-reported ASD severity level and adjusted for family sociodemographics. ASD prevalence estimates were 15.3 (NHW), 10.4 (NHB), 14.1 (Hispanic-English), and 5.2 (Hispanic-Other) per 1000 children. Mean diagnosis age was comparable across racial/ethnic/language groups for 3-4-year-olds. For 5-17-year-olds, diagnosis age varied by race/ethnicity/language and also by ASD severity. In this group, NHW children with mild/moderate ASD had a significantly higher proportion (50.8 %) of later diagnoses than NHB (33.5 %) or Hispanic-Other children (18.0 %). However, NHW children with severe ASD had a comparable or lower (albeit non-significant) proportion (16.4 %) of later diagnoses than NHB (37.8 %), Hispanic-English (30.8 %), and Hispanic-Other children (12.0 %). While NHW children have comparable ASD prevalence and diagnosis age distributions as Hispanic-English children, they have both higher prevalence and proportion of later diagnoses than NHB and Hispanic-Other children. The diagnosis age findings were limited to mild/moderate cases only. Thus, the prevalence disparity might be primarily driven by under-representation (potentially under-identification) of older children with mild/moderate ASD in the two minority groups.


Expression of the recombinant plasminogen activator (reteplase) by a non-lytic insect cell expression system.
Reteplase is a potent thrombolytic agent which is widely used in the management of acute myocardial infarction and stroke. It belongs to the third generation of the thrombolytic drugs and has been derived from native human tissue plasminogen activator by removing three domains of it and keeping the Kringle 2 and Serine protease domains. However, the high cost of this drug, has limited the application of this drug especially in the developing and third world countries. The most laborious steps in the bacterial production of this drug is its purification and refolding steps which keep the process yield low and the cost high. Therefore, in the present study we evaluated the expression of reteplase by a non-lytic insect cell expression system. Following cloning and transfection procedures, recombinant Sf9 insect cell clones expressing the reteplase protein were selected. Primarily, the expression was verified by dot-blot analysis and subsequently it was confirmed by Western Blotting showing a band of about 45 kD on nitrocellulose membrane. The biological activity of the expressed protein was also evaluated and showed to be about 29 IU/ml. This confirmed the possibility of expression and the correct folding of the expressed protein. Hence, optimization of the expression followed by purification of the protein could be the next steps of the study.


Analysis of patient states and state transitions.
Psychiatric diagnoses and formulations have classically focused on the chief complaint of the patient as part of a larger pattern of episodes and reactions. This is a form of state analysis in which the problem states of a person are carefully described and distinguished from other states. The authors suggest methods for deepening such formulations by grounding description of problem states in models of other states and models of state transitions. The resultant method of state analysis can be applied to examination of change processes during treatment as well as to initial diagnostic formulations. As an example of its use and possible extension to quantification, state analysis is applied to description of status and change in a person treated by brief psychotherapy. Because state analysis is based on observable behavior and reportable conscious experiences, it serves as a useful beginning point upon which to anchor more extended inferences about psychodynamics.


Hyperbaric oxygen for mild traumatic brain injury: Design and baseline summary.
The Brain Injury and Mechanisms of Action of Hyperbaric Oxygen for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (mTBI) (BIMA) study, sponsored by the Department of Defense, is a randomized double-blind, sham-controlled clinical trial that has a longer duration of follow-up and more comprehensive assessment battery compared to recent HBO₂ studies. BIMA randomized 71 participants from September 2012 to May 2014. Primary results are expected in 2017. Randomized military personnel received hyperbaric oxygen (HBO₂) at 1.5 atmospheres absolute (ATA) or sham chamber sessions at 1.2 ATA, air, for 60 minutes daily for 40 sessions. Outcomes include neuropsychological, neuroimaging, neurological, vestibular, autonomic function, electroencephalography, and visual systems evaluated at baseline, immediately following intervention at 13 weeks and six months with self-report symptom and quality of life questionnaires at 12 months, 24 months and 36 months. Characteristics include: median age 33 years (range 21-53); 99% male; 82% Caucasian; 49% diagnosed post-traumatic stress disorder; 28% with most recent injury three months to one year prior to enrollment; 32% blast injuries; and 73% multiple injuries. This manuscript describes the study design, outcome assessment battery, and baseline characteristics. Independent of a therapeutic role of HBO₂, results of BIMA will aid understanding of mTBI. ClinicalTrials.gov Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.


Carbon monoxide suppresses membrane expression of TLR4 via myeloid differentiation factor-2 in betaTC3 cells.
Islet allografts from donor mice exposed to CO are protected from immune rejection after transplantation via the suppression of membrane trafficking/activation of TLR4 in islets/beta cells. The molecular mechanisms of how CO suppresses TLR4 activation in beta cells remain unclear and are the focus of this study. Cells of the insulinoma cell line, betaTC3, were stably transfected with pcDNA3-TLR4-YFP and pDsRed-Monomer-Golgi plasmids and used to identify the subcellular distribution of TLR4 before and after LPS stimulation by confocal microscopy. Immunofluorescence analysis revealed that TLR4 mainly resides in the Golgi apparatus in betaTC3 cells when in a quiescent state. LPS stimulation led to a rapid trafficking of TLR4 from the Golgi to the cell membrane. Physical interaction between TLR4 and myeloid differentiation factor-2 (MD-2) was confirmed by immunoprecipitation. Depleting MD-2 using small interfering RNA or blocking the N-glycosylation of cells using tunicamycin blocked membrane trafficking of TLR4. Pre-exposing cells to CO at a concentration of 250 parts per million suppressed membrane trafficking of TLR4 via inhibiting its glycosylation and the interaction between TLR4 and MD-2. In conclusion, MD-2 is required for the glycosylation of TLR4 and its consequent membrane trafficking in betaTC3 cells. CO suppresses membrane activation of TLR4 via blocking its glycosylation and the physical interaction between TLR4 and MD-2.


[Multiple brain abscesses in the territory of the vertebral-basilar artery resulting from an infected aortic arch graft].
A 62-year-old man with high fever and in a state of disorientation was transferred to our hospital. One year before this transfer, he had undergone total arch replacement surgery for thoracic aortic dissection. On admission to our hospital, head MRI revealed multiple brain abscesses in the territory of the vertebral-basilar artery, and chest CT showed gas around the aortic graft, in particular, at the origin of the left subclavian artery. We diagnosed him with brain abscesses in the left vertebral-basilar artery resulting from an infected aortic graft. We immediately began administration of intravenous antibiotics. Although his blood, urine, and cerebrospinal fluid cultures were negative, fortunately, the brain abscesses and ectopic gas disappeared. Since reports of only antibiotic use for treating brain abscesses due to aortic graft infection are rare, the appropriate duration of antibiotic administration has not been established yet. Therefore, careful observation is required in this case.


Addressing the Environment Electrostatic Effect on Ballistic Electron Transport in Large Systems: A QM/MM-NEGF Approach.
The effects of the environment in nanoscopic materials can play a crucial role in device design. Particularly in biosensors, where the system is usually embedded in a solution, water and ions have to be taken into consideration in atomistic simulations of electronic transport for a realistic description of the system. In this work, we present a methodology that combines quantum mechanics/molecular mechanics methods (QM/MM) with the nonequilibrium Green's function framework to simulate the electronic transport properties of nanoscopic devices in the presence of solvents. As a case in point, we present further results for DNA translocation through a graphene nanopore. In particular, we take a closer look into general assumptions in a previous work. For this sake, we consider larger QM regions that include the first two solvation shells and investigate the effects of adding extra k-points to the NEGF calculations. The transverse conductance is then calculated in a prototype sequencing device in order to highlight the effects of the solvent.


Women's knowledge of Pap smear test and human papillomavirus: acceptance of HPV vaccination to themselves and their daughters in an Islamic society.
Cancer of cervix uteri is the second most common cancer among women, and it has been shown to be caused by human papillomavirus (HPV) infection in more than 99% of cases. We surveyed Muslim Turkish women, who mostly accept talking about sex as a taboo, to examine their knowledge about Papanicolaou (Pap) smear test, HPV, HPV vaccine, and their attitude toward vaccination to themselves and their daughters. We surveyed 525 women aged between 19 and 53 years to examine their knowledge about cervical cancer screening Pap smear test, HPV, HPV vaccine, and their attitude toward vaccination to themselves and their daughters with a questionnaire that is consisted of 5 parts with a total of 31 items. The knowledge of cervical screening was high (70%), and 51% of the subjects were at least once had a Pap smear test, but most respondents (56%) had never heard of HPV. For most women, recommendations from health workers (67%) were the major influences in deciding to get vaccinated. The importance of successful introduction on the vaccine by the drug providers and health care professionals in Turkey was shown in this present study with a high rate of awareness of cervical cancer vaccine. "Early-age vaccination knowledge" before any sexual contact is probably due to the correct education of mothers by health care professionals. The professionals should be educated and trained about HPV, vaccination, and its relation with cervical cancer to increase the knowledge about it.


Prediction of thermal boundary resistance by the machine learning method.
Thermal boundary resistance (TBR) is a key property for the thermal management of high power micro- and opto-electronic devices and for the development of high efficiency thermal barrier coatings and thermoelectric materials. Prediction of TBR is important for guiding the discovery of interfaces with very low or very high TBR. In this study, we report the prediction of TBR by the machine learning method. We trained machine learning models using the collected experimental TBR data as training data and materials properties that might affect TBR as descriptors. We found that the machine learning models have much better predictive accuracy than the commonly used acoustic mismatch model and diffuse mismatch model. Among the trained models, the Gaussian process regression and the support vector regression models have better predictive accuracy. Also, by comparing the prediction results using different descriptor sets, we found that the film thickness is an important descriptor in the prediction of TBR. These results indicate that machine learning is an accurate and cost-effective method for the prediction of TBR.


Cholesterol metabolism in the macrophage. 3. Ingestion and intracellular fate of cholesterol and cholesterol esters.
Phagocytosis of cholesterol-containing particles resulted in the formation of an intralysosomal cholesterol compartment. Cholesterol was excreted out of the macrophage with a single exponential rate which depended on the concentration of acceptor lipoproteins in the medium. Exchange kinetics performed on cells which had ingested particulate cholesterol suggested that excretion occurred by the same mechanism as exchange. Cholesterol esters as particulate albumin coacervates were taken up by macrophages and hydrolyzed by a lysosomal cholesterol esterase with optimal activity at pH 4.0. Cholesteryl linoleate was hydrolyzed much more readily than cholesteryl palmitate. The amount of cholesterol esterase and its specific activity increased during the in vitro cultivation of macrophages. Intralysosomally, cholesteryl linoleate and palmitate were hydrolyzed to free cholesterol which was excreted from the macrophage and recovered in the medium. Since cholesteryl linoleate was hydrolyzed more rapidly than free cholesterol was excreted into the medium, free cholesterol accumulated intralysosomally. Cholesteryl palmitate was hydrolyzed more slowly, and the rate of hydrolysis was limiting for excretion of the free cholesterol from within the lysosome.


Parental and social factors in relation to child psychopathology, behavior, and cognitive function.
Parental and social factors have long-term impact on the neurodevelopment of offspring, but tend to highly covary with each other. Thus, it is difficult to parse out which parental and social factor contributes most to neurodevelopmental outcomes. This study aimed to assess clusters of parental and social factors associated with child psychopathology, behavioral problems, and cognition. This study employed the data of 11,875 children (9 to 11 years) from the Adolescent Brain Cognitive Development (ABCD) study. Principal component analysis (PCA) was performed on 39 environmental measures and 30 child behavior and cognitive measures separately to identify clusters of parental and social factors and clusters of child psychopathology, behaviour, and cognition. Regression analysis was used to examine independent effects of each cluster of parental and social factors on child psychopathology, behavioral problems, and cognition. Greater Parent Psychopathology cluster was associated with greater Child Psychopathology cluster. Moreover, greater Socioeconomic Status cluster was associated with greater child General Cognition and Executive Function but less Behavioral Inhibition clusters. Greater Proximal Social Environment and Interaction cluster were associated with less child Impulsive Behavior and Behavioral Inhibition, but greater Behavioral Activation cluster. The environmental clusters related to birth outcomes, maternal tobacco, and drug use were not significantly related to child psychopathology, behavior, and cognition. Our findings suggest that socioeconomic status, parental psychopathology, and social environment and interactions are the strongest risks for behavioral problems and cognitive performance in a general child population. Intervention programs should target modifiable factors within these domains.


Integration strategies in transition: an interview with Russell C. Coile, Jr.
Russell C. Coile, Jr., is a nationally recognized futurist and speaker specializing in healthcare business strategy and market forecasting, and vice president and national strategy consultant for Southfield, Michigan-based Superior Consultant Company, Inc. Coile also has written seven books dealing with the future of health care, including New Century Healthcare: Strategies for Providers, Purchasers, and Plans, which was published this year. Coile spoke with HFM to share his views regarding the future of IDSs and how these organizations may need to modify their strategies to ensure their long-term financial success.


SARM1 activation triggers axon degeneration locally via NAD⁺ destruction.
Axon degeneration is an intrinsic self-destruction program that underlies axon loss during injury and disease. Sterile alpha and TIR motif-containing 1 (SARM1) protein is an essential mediator of axon degeneration. We report that SARM1 initiates a local destruction program involving rapid breakdown of nicotinamide adenine dinucleotide (NAD(+)) after injury. We used an engineered protease-sensitized SARM1 to demonstrate that SARM1 activity is required after axon injury to induce axon degeneration. Dimerization of the Toll-interleukin receptor (TIR) domain of SARM1 alone was sufficient to induce locally mediated axon degeneration. Formation of the SARM1 TIR dimer triggered rapid breakdown of NAD(+), whereas SARM1-induced axon destruction could be counteracted by increased NAD(+) synthesis. SARM1-induced depletion of NAD(+) may explain the potent axon protection in Wallerian degeneration slow (Wld(s)) mutant mice.


Multiple toll-like receptors (TLRs) display differential bacterial and ligand specificity in the earthworm, Eisenia andrei.
Toll-like receptors (TLRs), an ancient and well-conserved group of pattern recognition receptors (PRRs), recognize conserved pathogen-associated molecular patterns. TLRs consist of three domains: the extracellular N-terminal domain, containing one or more leucine-rich repeats (LRRs), responsible for the recognizing and binding of antigens; the type-I transmembrane domain; and the intracellular domain known as the Toll/Interleukin-1 receptor (TIR) domain required for the downstream signaling pathway. We identified six new full-length complementary DNA (cDNA) sequences, Ean-TLR1/2/3/4/5/6. The deduced amino acid sequences indicate that Ean-TLRs consist of one signal peptide, one LRR N-terminal domain (Ean-TLR4/5), varying numbers of LRRs, one (Ean-TLR1/2/3/4/5) or two (Ean-TLR6) LRR C-terminal domains, one type-I transmembrane domain, and a TIR domain. In addition, a TIR domain alignment revealed that three conserved motifs, designated as Box 1, Box 2, and Box 3, contain essential amino acid residues for downstream signaling activity. Phylogenetic analysis of earthworm TLRs generated two separate evolutionary branches representing single (sccTLR) and multiple (mccTLR) cysteine cluster TLRs. Ean-TLR1/2/3/4 (sccTLR type) and Ean-TLR6 (mccTLR type) were clustered with corresponding types of previously reported earthworm TLRs as well as TLRs from Clitellata and Polychaete. As PRRs, earthworm TLRs should be capable of sensing a diverse range of pathogens. Except for Ean-TLR3, which was not responsive to any bacteria, earthworm TLR expression was significantly induced by Gram-positive but not Gram-negative bacteria. Moreover, it is likely that earthworms can differentiate between different species of Gram-positive bacteria via their TLR responses. The ligand specificity of earthworm TLRs suggests that their pathogenic ligand recognition is likely to be as specific and diverse as the mammalian TLR pathogen-sensing system.


Rat placental lactogen II gene: characterization of gene structure and placental-specific expression.
Rat placental lactogen II (rPLII) was the first described member of the rat PRL-like placental gene family in which nine novel proteins have now been identified. In this article, we present data on the isolation and characterization of the rPLII gene. Two genomic clones, GC I (18.5 kb) and GC II (9.4 kb), were isolated from an EMBL3 Sprague-Dawley rat liver genomic DNA library. GC I, which was used for further analysis, contains the entire coding region and extensive 5' and 3' flanking information. The rPLII gene, estimated to be 5.4 kb in size, has the same five-exon and four-intron structure and identical intron/exon splice sites and types as the rPRL gene. A major transcription start site 58 bp upstream of the initiator methionine codon and several minor sites 1-3 bp 5' and 3' of this site were identified by primer extension of day 18 placental messenger RNA. The rPLII gene has been localized to chromosome 17, using a series of hybrid cell lines derived from mouse hepatoma cells (MWTG3) and adult rat hepatocytes; this is the same chromosome designation as the PRL gene itself and other cloned placental members of this gene family. Luciferase reporter constructs containing 5' flanking DNA sequences were tested in transient transfection assays in the rat choriocarcinoma cell line, Rcho, and the rat pituitary GC cell line. Both a 4.5- and 3-kb 5' flanking sequence supported luciferase expression in the Rcho but not the GC cells. A 765-bp fragment showed no activity in either cell type. Transient transgenic mice, generated with the 3-kb 5' rPLII/luciferase construct, expressed varying amounts of luciferase expression in the placenta.


Higher Body Mass Index Is Associated with Lower Cortical Amyloid-β Burden in Cognitively Normal Individuals in Late-Life.
Both low and high body mass index (BMI) have been associated with an increased risk of dementia, including that caused by Alzheimer's disease (AD). Specifically, high middle-age BMI or a low late-age BMI has been considered a predictor for the development of AD dementia. Less studied is the relationship between BMI and AD pathology. We explored the association between BMI and cortical amyloid-β (Aβ) burden in cognitively normal participants that were either in mid-life (45-60 years) or late-life (>60). We analyzed cross-sectional baseline data from the Knight Alzheimer Disease Research Center (ADRC) at Washington University. Aβ pathology was measured in 373 individuals with Aβ PET imaging and was quantified using Centiloid units. We split the cohort into mid- and late-life groups for analyses (n = 96 and n = 277, respectively). We ran general linear regression models to predict Aβ levels from BMI while controlling for age, sex, years of education, and APOE4 status. Analyses were also conducted to test the interaction between BMI and APOE4 genotype and between BMI and sex. Higher BMI was associated with lower cortical Aβ burden in late-life (β= -0.81, p = 0.0066), but no relationship was found in mid-life (β= 0.04, p > 0.5). The BMI×APOE4+ and BMI×male interaction terms were not significant in the mid-life (β= 0.28, p = 0.41; β= 0.64, p = 0.13) or the late-life (β= 0.17, p > 0.5; β= 0.50, p = 0.43) groups. Higher late-life BMI is associated with lower cortical Aβ burden in cognitively normal individuals.


Socioeconomic factors impact quality of life outcomes and olfactory measures in chronic rhinosinusitis.
Healthcare disparities related to socioeconomic factors may adversely impact disease states and treatment outcomes. Among patients with chronic rhinosinusitis (CRS), the impact of socioeconomic factors on outcomes following endoscopic sinus surgery (ESS) remains uncertain. Adult patients with refractory CRS were prospectively enrolled into an observational, multi-institutional cohort study between March 2011 and June 2015. Socioeconomic factors analyzed included household income, insurance status, years of education completed, race, age, and ethnicity. Income was stratified according to the Thompson and Hickey model. The 22-item Sino-Nasal Outcome Test (SNOT-22) and Brief Smell Identification Test (BSIT) were completed preoperatively and postoperatively. A total of 392 patients met inclusion criteria. Higher age and male gender were associated with better mean preoperative SNOT-22 scores (both p < 0.02), whereas Medicare insurance status and male gender were associated with worse preoperative mean BSIT scores (both p < 0.02). Postoperatively, higher household income ($100,001+/year) and lower age were associated with a greater likelihood of improving at least 1 minimal clinically important difference (MCID) on SNOT-22 scores (OR = 2.40 and 1.03, respectively, both p < 0.05), while no factors were associated with increased odds of achieving a MCID on BSIT scores. Preoperative olfactory function and postoperative quality of life (QOL) improvement were associated with metrics of socioeconomic status in patients with CRS electing ESS. The odds of experiencing a clinically meaningful QOL improvement were more than twice as likely for patients with the highest household income level compared to other income tiers. Further investigation is warranted to identify barriers to postoperative improvement.


The effect of traumatic brain injury on the timing of sleep.
While there have been single case reports of the development of circadian rhythm sleep disorders, most commonly delayed sleep phase syndrome following traumatic brain injury (TBI), to our knowledge there have been no group investigations of changes to sleep timing in this population. The aim of the present study was to investigate sleep timing following TBI using the dim light melatonin onset (DLMO) as a marker of circadian phase and the Morningness-Eveningness Questionnaire (MEQ) as a measure of sleep-wake behavior. A sleep-wake diary was also completed. It was hypothesized that the timing of DLMO would be delayed and that there would be a greater tendency toward eveningness on the MEQ in a post-acute TBI group (n=10) compared to a gender and age matched control group. Participants were recruited at routine outpatient review appointments (TBI) and from the general population (control) as part of a larger study. They attended the sleep laboratory where questionnaires were completed, some retrospectively, and saliva melatonin samples were collected half-hourly according to a standard protocol. The results show that the TBI and control groups reported similar habitual sleep times and this was reflected on the MEQ. There was, however, significant variability in the TBI group's change from the pre-injury to the current MEQ score. The timing of melatonin onset was not different between the groups. While subtle changes (advances or delays) in this small sample may have cancelled each other out,. the present study does not provide conclusive objective evidence of shift in circadian timing of sleep following TBI. Furthermore, although participants did report sleep timing changes, it is concluded that the MEQ may not be suitable for use with this cognitively impaired clinical group.


Modeling and Density Estimation of an Urban Freeway Network Based on Dynamic Graph Hybrid Automata.
In this paper, in order to describe complex network systems, we firstly propose a general modeling framework by combining a dynamic graph with hybrid automata and thus name it Dynamic Graph Hybrid Automata (DGHA). Then we apply this framework to model traffic flow over an urban freeway network by embedding the Cell Transmission Model (CTM) into the DGHA. With a modeling procedure, we adopt a dual digraph of road network structure to describe the road topology, use linear hybrid automata to describe multi-modes of dynamic densities in road segments and transform the nonlinear expressions of the transmitted traffic flow between two road segments into piecewise linear functions in terms of multi-mode switchings. This modeling procedure is modularized and rule-based, and thus is easily-extensible with the help of a combination algorithm for the dynamics of traffic flow. It can describe the dynamics of traffic flow over an urban freeway network with arbitrary topology structures and sizes. Next we analyze mode types and number in the model of the whole freeway network, and deduce a Piecewise Affine Linear System (PWALS) model. Furthermore, based on the PWALS model, a multi-mode switched state observer is designed to estimate the traffic densities of the freeway network, where a set of observer gain matrices are computed by using the Lyapunov function approach. As an example, we utilize the PWALS model and the corresponding switched state observer to traffic flow over Beijing third ring road. In order to clearly interpret the principle of the proposed method and avoid computational complexity, we adopt a simplified version of Beijing third ring road. Practical application for a large-scale road network will be implemented by decentralized modeling approach and distributed observer designing in the future research.


Moderate-Intensity Intermittent External Volume Expansion Optimizes the Soft-Tissue Response in a Murine Model.
Intermittent external volume expansion using suction enhances the vascular network of soft tissues, possibly increasing fat graft survival. However, the optimal kinetics of application have not been determined. Based on their previous experience, the authors hypothesized that moderate-intensity intermittent external volume expansion application may further enhance both the angiogenic and adipogenic potential. Fifty 12-week-old wild-type mice were assigned to five experimental groups (n = 10 per group) and underwent five different intermittent applications of external volume expansion (i.e., single-application control, low-intensity, moderate-intensity, and two groups of high-intensity). Five days after the final stimulation, skin biopsy specimens were obtained from stimulated and contralateral nonstimulated areas. Microscopic sections were analyzed for angiogenesis, skin remodeling, and adipogenesis. Moderate-intensity intermittent stimulation (0.5 hour, 6 times/day for 5 days at -25 mmHg suction) almost doubled cutaneous vascular density (1.9-fold increase), induced skin thickening (1.9-fold increase), and expanded the subcutaneous tissue (2.3-fold increase) compared with control. External volume expansion kinetics did not affect tissue inflammation at 5 days after treatment. High-intensity intermittent stimulations also increased the density of blood vessels (1.6-fold increase compared with controls) but caused tissue damage, whereas low-intensity external volume expansion did not induce significant changes. Application of moderate-intensity intermittent external volume expansion optimizes induction of angiogenesis and adipogenesis in soft tissues without tissue damage, holding potential for time-effective recipient-site preconditioning before fat grafting.


A machine learning study of the two states model for lipid bilayer phase transitions.
We have adapted a set of classification algorithms, also known as machine learning, to the identification of fluid and gel domains close to the main transition of dipalmitoyl-phosphatidylcholine (DPPC) bilayers. Using atomistic molecular dynamics conformations in the low and high temperature phases as learning sets, the algorithm was trained to categorise individual lipid configurations as fluid or gel, in relation with the usual two-states phenomenological description of the lipid melting transition. We demonstrate that our machine can learn and sort lipids according to their most likely state without prior assumption regarding the nature of the order parameter of the transition. Results from our machine learning study provide strong support in favour of a two-states model approach of membrane fluidity.


Social Practice and Shared History, Not Social Scale, Structure Cross-Cultural Complexity in Kinship Systems.
Human populations display remarkable diversity in language and culture, but the variation is not without limit. At the population level, variation between societies may be structured by a range of macro-evolutionary factors, including ecological and environmental resources, shared ancestry, spatial proximity, and covarying social practices. Kinship terminology systems are varying linguistic paradigms that denote familial social relationships of kin and non-kin. Systems vary by the kinds of salient distinctions that are made (e.g., age, gender, generation) and the extent to which different kinds of kin are called by the same term. Here, we explore two kinds of explanations for an observed typology of kin terms for cousins. The first one derives the typology from a learning bottleneck linked to population size. This would lead to a correlation between community size and the type of kinship system. The second one derives it from a set of social practices, particularly marriage and transfer of resources that might shape kinship systems. Using a global ethnographic database of over a thousand societies, we show that marriage rules and shared linguistic affiliation have a significant influence on the type of kinship system found in a society. This remains true if we control for the effect of spatial proximity and cultural ancestry. By combining cognitive and historic approaches to this aspect of kinship, we suggest broader implications for the study of human social cognition in general.


Needs assessment of persons with multiple sclerosis and significant others: using the literature review and focus groups for preliminary survey questionnaire development.
The purpose of this study was to conduct focus group interviews to obtain information for development of a needs assessment questionnaire. Four focus groups were conducted with 10 people with multiple sclerosis (MS) and five significant others. A facilitator from the learning services department at the hospital conducted the interviews guided by questions developed by the researcher. The focus group interviews were audiotaped and transcribed. The researcher analyzed the transcribed interviews. Content analysis was used to analyze the transcribed data creating categories from key words and phrases as they appeared. The findings were grouped by themes. The results highlighted the participants' experiences and needs regarding physical changes; sources of assistance; unmet needs; psychological, employment, leisure, and informational needs. A comparison of themes developed from the focus groups and in the literature captured categories for questionnaire development. One new theme, leisure, was not found in the literature and was incorporated based on the findings of this study. The final categories for questionnaire development were: physical, health, psychological, financial, employment/meaningful daytime activity and leisure, accessibility and information. A survey questionnaire was developed from the focus group data using the phraseology of the participants.


A novel finite spectral entropy: Gated term memory unit recursive network integrated with Ladybug Beetle Optimization algorithm for epileptic seizure detection.
Professional medical experts use a visual electroencephalography (EEG) signal for epileptic seizure detection, although this method is time-consuming and highly subject to bias. The majority of previous epileptic detection techniques have poor efficiency, detection performance and also which are unsuited to handle large datasets. In order to solve the aforementioned issues and to assist medical professionals with an advanced technology, a computerized epileptic seizure detection system is essential. Therefore, the proposed work intends to design an automated detection tool for predicting an epileptic seizure from EEG signals. For this purpose, a novel non-linear feature analysis and deep learning algorithms are deployed in this work. Initially, the signal decomposition, filtering and artifacts removal operations are carried out with the use of finite Haar wavelet transformation technique. After that, the finite spectral entropy (FSE) based feature extraction model has been used to extract the time, frequency, and time-frequency features from the normalized signal. Consequently, the novel gated term memory unit recursive network (GTRN) model is employed to predict the given EEG signal as whether healthy or seizure affected including the class with high accuracy. During this process, the recently developed Ladybug Beetle Optimization (LBO) algorithm is used to compute the logistic sigmoid function based on the solution. The purpose of using this algorithm is to simplify the process of classification with increased seizure prediction accuracy and performance. Moreover, the standard and popular benchmark EEG datasets are used to validate and test the results of the proposed FSE-GTRN-LBO mechanism. By leveraging the finite Haar wavelet transformation and FSE-based feature extraction, we can efficiently process EEG signals. The utilization of the GTRN model enables accurate classification of healthy and seizure-affected EEG data. To optimize the classification process further, we integrate the LBO algorithm, streamlining the computation of the logistic sigmoid function. Through comprehensive validation on standard EEG datasets, our proposed FSE-GTRN-LBO mechanism achieves outstanding seizure prediction accuracy and performance, surpassing existing state-of-the-art techniques.


The influence of self-absorption on PET and PET/CT shielding requirements.
The high energy (511 keV) annihilation photons used in positron emission tomography (PET) imaging generally require a substantial amount of lead to protect personnel and the general public from ionizing radiation. A cost-effective design of the PET facility that ensures radiation does not exceed formal dose limits requires accurate estimation of the necessary PET shielding. The American Association of Physicists in Medicine (AAPM) Task Group 108 recently published broad beam transmission factors based on Monte Carlo calculations of 511 keV photons. In this work, an extension to the AAPM model is presented, based on Monte Carlo simulations including the effects of self-absorption on the photon energy spectrum. Monte Carlo calculations were performed using MCNPX. The photon energy spectrum after self-absorption was computed by simulating a normal 18FDG activity distribution in an anthropomorphic phantom. This spectrum was used to calculate the dose rate transmission factors for various wall thicknesses of lead, concrete, and iron. The method was validated by measurement and corresponding simulation of the transmission factors of an 18FDG source in air and in PMMA. Furthermore, a method to generate 3D area dose rate maps of PET facilities incorporating the calculated transmission tables is presented and applied to several shielding situations. The calculated self-absorption correction factor and the broad beam transmission factors resulting from Monte Carlo simulations of a monoenergetic point source emitting 511 keV photons were in excellent agreement with the results of the AAPM publication (0.66 vs 0.64 and R2 = 0.999, respectively). However, when all radiation physics, i.e., also the effect of self-absorption on the photon energy spectrum, is included in the Monte Carlo calculations, a substantial reduction in required shielding material was found. For example, including all radiation physics leads to 13.3 mm of lead required to obtain a typical transmission factor of 0.1, instead of 16.0 mm of lead when the AAPM data including only the self-absorption correction factor are used. These findings were confirmed by the experimental measurements. The transmission factors produced in this work can be applied in the same manner as those estimated by AAPM to allow for a cost-effective design of PET and PET/CT facilities without violating radiation safety regulations. Taking into account the effect of self-absorption on the photon energy spectrum results in more accurate and cost-effective shielding requirement estimations.


Enriched environment as a nonpharmacological neuroprotective strategy.
The structure and functions of the central nervous system are influenced by environmental stimuli, which also play an important role in brain diseases. Enriched environment (EE) consists of producing modifications in the environment of standard laboratory animals to induce an improvement in their biological conditions. This paradigm promotes transcriptional and translational effects that result in ameliorated motor, sensory, and cognitive stimulation. EE has been shown to enhance experience-dependent cellular plasticity and cognitive performance in animals housed under these conditions compared with animals housed under standard conditions. In addition, several studies claim that EE induces nerve repair by restoring functional activities through morphological, cellular, and molecular adaptations in the brain that have clinical relevance in neurological and psychiatric disorders. In fact, the effects of EE have been studied in different animal models of psychiatric and neurological diseases, such as Alzheimer's disease, Parkinson's disease, schizophrenia, ischemic brain injury, or traumatic brain injury, delaying the onset and progression of a wide variety of symptoms of these disorders. In this review, we analyze the action of EE focused on diseases of the central nervous system and the translation to humans to develop a bridge to its application.


Exploring Information Available to and Used by Physicians on Antibiotic Use and Antibiotic Resistance in Jordan.
Evidence based information sources for physicians are needed for informed antibiotic prescribing practices. The aim of this study was to explore physicians' preferred sources of information and evaluate physicians' awareness of available information and initiatives on prudent antibiotic prescribing in Jordan. A cross-sectional study was conducted utilizing an online questionnaire and included physicians (n = 409) from all sectors and specialties in Jordan. Published guidelines (31.8%), the workplace (25.7%), colleagues or peers (20.0%), group or conference training (18.3%), and the medical professional body (18.1%) were the main sources of information about avoiding unnecessary antibiotic prescribing, with the influence of these sources on changing prescribers' views being 34.7%, 17.1%, 11%, 13.4%, and 7.6%, respectively. One-third of physicians (33.7%) reported no knowledge of any initiatives on antibiotic awareness and resistance. Regarding awareness of national action plans on antimicrobial resistance, 10.5%, 34%, and 55.5% of physicians were aware, unaware, and unsure of the presence of any national action plans, respectively. Physicians showed interest in receiving more information on resistance to antibiotics (58.9%), how to use antibiotics (42.2%), medical conditions for which antibiotics are used (41.3%), prescribing of antibiotics (35.2%), and links between the health of humans, animals, and the environment (19.8%). The findings can inform interventions needed to design effective antimicrobial stewardship, enabling physicians to prescribe antibiotics appropriately.


Race/Ethnic Differences in Effects of Family Instability on Adolescents' Risk Behavior.
We used data from the National Longitudinal Study of Adolescent Health (N = 7,686) to determine whether racial and ethnic differences in socioeconomic stress and social protection explained group differences in the association between family structure instability and three risk behaviors for White, Black, and Mexican American adolescents: delinquent behavior, age at first nonmarital sex, and age at first nonmarital birth. The positive association between mothers' union transitions and each outcome for White adolescents was attenuated by social protection. The association of instability with age at first sex and first nonmarital birth was weaker for Black adolescents, but not for Mexican American adolescents. The weaker association was explained by Black adolescents' more frequent exposure to socioeconomic stress in the context of union instability.


Dynorphin A elicits an increase in intracellular calcium in cultured neurons via a non-opioid, non-NMDA mechanism.
The opioid peptide dynorphin A is known to elicit a number of pathological effects that may result from neuronal excitotoxicity. An up-regulation of this peptide has also been causally related to the dysesthesia associated with inflammation and nerve injury. These effects of dynorphin A are not mediated through opioid receptor activation but can be effectively blocked by pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists, thus implicating the excitatory amino acid system as a mediator of the actions of dynorphin A and/or its fragments. A direct interaction between dynorphin A and the NMDA receptors has been well established; however the physiological relevance of this interaction remains equivocal. This study examined whether dynorphin A elicits a neuronal excitatory effect that may underlie its activation of the NMDA receptors. Calcium imaging of individual cultured cortical neurons showed that the nonopioid peptide dynorphin A(2-17) induced a time- and dose-dependent increase in intracellular calcium. This excitatory effect of dynorphin A(2-17) was insensitive to (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine (MK-801) pretreatment in NMDA-responsive cells. Thus dynorphin A stimulates neuronal cells via a nonopioid, non-NMDA mechanism. This excitatory action of dynorphin A could modulate NMDA receptor activity in vivo by enhancing excitatory neurotransmitter release or by potentiating NMDA receptor function in a calcium-dependent manner. Further characterization of this novel site of action of dynorphin A may provide new insight into the underlying mechanisms of dynorphin excitotoxicity and its pathological role in neuropathy.


Limited-stage mantle cell lymphoma: treatment outcomes at the Princess Margaret Hospital.
Mantle-cell lymphoma (MCL) is a rare cancer, with the majority of patients (pts) presenting in stage III-IV and the outcomes are poor. To determine the curability of localized MCL, we examine stage I-II pts at our institution between 1990-2007. 26 pts with stage I (38%) and stage II (62%) were referred. Sites involved were head and neck in 73%. Five had a blastoid variant. Five patients were treated with palliative intent. Analysis was focused on pts treated with a curative intent (21 pts): 17 CT+RT, 2 RT, 2 CT followed by ASCT. 13 patients received CHOP, 5-RCHOP, 1-CVP; most received 6 cycles. The RT median dose was 35Gy and IFRT for the majority. For 21 pts treated with a curative intent, median follow up was 5.8 years. The overall response rate was 95%. Among the 19 CR/CRu pts, 9 relapsed for a 5-year relapse rate of 46%. Relapses were mainly observed at distant sites, 3 were in GI tract, 1 had both local and distant relapse. Median PFS and OS were 3.2 and 6.4 years, respectively. 5-year OS was 62%. In univariate analysis, blastoid variant and stage II were prognostic factors for PFS. Multivariate analysis could not be performed due to the small sample size. With a treatment approach using combined CT+RT for stage I-II MCL, local control was achieved in 94%. Systemic relapse remains a significant problem, especially for stage II and blastoid variant. Radiotherapy should remain part of curative treatment plan in stage I-II MCL.


Review. Establishing an experimental science of culture: animal social diffusion experiments.
A growing set of observational studies documenting putative cultural variations in wild animal populations has been complemented by experimental studies that can more rigorously distinguish between social and individual learning. However, these experiments typically examine only what one animal learns from another. Since the spread of culture is inherently a group-level phenomenon, greater validity can be achieved through 'diffusion experiments', in which founder behaviours are experimentally manipulated and their spread across multiple individuals tested. Here we review the existing corpus of 33 such studies in fishes, birds, rodents and primates and offer the first systematic analysis of the diversity of experimental designs that have arisen. We distinguish three main transmission designs and seven different experimental/control approaches, generating an array with 21 possible cells, 15 of which are currently represented by published studies. Most but not all of the adequately controlled diffusion experiments have provided robust evidence for cultural transmission in at least some taxa, with transmission spreading across populations of up to 24 individuals and along chains of up to 14 transmission events. We survey the achievements of this work, its prospects for the future and its relationship to diffusion studies with humans discussed in this theme issue and elsewhere.


[Pregnancy with an extremely rare P blood group with anti-PP1Pk].
The authors report on a successful pregnancy in a young Turkish patient with p and anti-PP1Pk-antibodies. Anti-PP1Pk is considered to cause haemolytic diseases in the newborn and habitual abortions. The patient was treated via plasma exchange and substitution with intravenous immunoglobulin. At 31 weeks of gestation the patient underwent Caesarean section due to growth retardation and pathological signs in the fetal CTG. The child has developed well up to two years after the delivery. Based on our data and a review of the literature, the effectiveness of therapy by plasmapheresis and/or immunoglobulin is discussed.


[Effect of ambroxol on surfactant secretion and synthesis in isolated type II alveolar cells].
The effect of ambroxol is attributed in part to an effect on surfactant synthesis and secretion. Evidence supporting this hypothesis is largely indirect; a direct effect of ambroxol on surfactant synthesis and secretion remains to be demonstrated. In this study a direct effect of ambroxol was evaluated using isolated alveolar type II cells. Secretion of labelled phosphatidylcholine was measured following the addition of increasing concentrations (10(-8) M to 10(-4) M) of ambroxol to the culture medium for increasing time intervals. There was no significant increase in surfactant secretion with increased ambroxol concentration or prolonged exposure time. Uptake of 3H-choline and synthesis into 3H-phosphatidylcholine was analyzed as an indicator of surfactant synthesis. Again, increasing concentrations of ambroxol (10(-7) M to 10(-5) M) were followed for 1, 2, 4, 8 and 24 h. There was no significant effect on synthesis at any time point. Concentrations higher than those mentioned here resulted in LDH release from cultured cells. Ambroxol which also has anti-oxidative and anti-inflammatory effects does not exhibit direct stimulatory effects on surfactant synthesis and secretion in isolated (rat) alveolar type II cells as has been demonstrated e.g. for beta 2-adrenergic stimulation. A specific pharmacologic way to stimulate the surfactant system remains to be developed.


Histologic and clinical comparison of bilateral sinus floor elevations with and without barrier membrane placement in 12 patients: Part 3 of an ongoing prospective study.
In 1993 the Department of Implant Dentistry at New York University College of Dentistry began a long-term clinical, histologic, histomorphometric, and radiographic study of the sinus elevation procedure. One of the parameters under evaluation in this study is the effect of barrier membrane placement on the creation of vital bone in the grafted sinus cavity. This report presents a histologic and histomorphometric evaluation of healing with and without the placement of an expanded polytetrafluoroethylene (e-PTFE) barrier membrane over the lateral window at the time of sinus grafting. The data were collected from 12 patients who underwent bilateral sinus elevation surgery. In each of these 12 patients the same grafting material was used in both sinuses, making the presence or absence of an e-PTFE barrier membrane the only controlled variable. Under the conditions of this study, the results indicate that (1) placement of the barrier membrane tends to increase vital bone formation; (2) placement of a barrier membrane has a positive effect on implant survival; and (3) membrane placement should be considered for all sinus elevation procedures.


Oxygen binding by single crystals of hemoglobin: the problem of cooperativity and inequivalence of alpha and beta subunits.
Oxygen binding by the human hemoglobin tetramer in the T quaternary structure is apparently noncooperative in the crystalline state (Hill n = 1.0), as predicted by the two-state allosteric model of Monod, Wyman, and Changeux (MWC) (Mozzarelli et al., Nature 351:416-419, 1991; Rivetti et al., Biochemistry 32:2888-2906, 1993). However, cooperativity within the tetramer can be masked by a difference in affinity between the alpha and beta subunits. Indeed, analysis of the binding curves derived from absorption of light polarized along two different crystal directions, for which the projections of the alpha and beta hemes are slightly different, revealed an inequivalence in the intrinsic oxygen affinity of the alpha and beta subunits (p50(alpha) approximately 80 torr, p50(beta) approximately 370 torr at 15 degrees C) that compensates a small amount of cooperativity (Rivetti et al., Biochemistry 32:2888-2906, 1993). To further investigate this problem, we have measured oxygen binding curves of single crystals of hemoglobin (in a different lattice) in which the iron in the alpha subunits has been replaced by the non-oxygen-binding nickel(II). The Hill n is 0.90 +/- 0.06, and the p50 is slightly different for light polarized parallel to different crystal directions, indicating a very small difference in affinity between the two crystallographically inequivalent beta subunits. The average crystal p50 is 110 +/- 20 torr at 15 degrees C, close to the p50 of 80 torr observed in solution, but about threefold less than the p50 calculated by Rivetti et al. (Biochemistry 32:2888-2906, 1993) for the beta subunits of the unsubstituted tetramer. These results suggest that Rivetti et al., if anything, overestimated the alpha/beta inequivalence. They therefore did not underestimate the cooperativity within the T quaternary structure, when they concluded that it represents a small deviation from the perfectly noncooperative binding of an MWC allosteric model. Our conclusion of nearly perfect MWC behavior for binding to the T state of unmodified hemoglobin raises the question of the relevance of the large T-state cooperativity inferred for cyanide binding to partially oxidized hemoglobin (Ackers et al., Science 255:54-63, 1992).


Screening migrants for tuberculosis - a missed opportunity for improving knowledge and attitudes in high-risk groups: A cross-sectional study of Swedish-language students in Umeå, Sweden.
Migrants from countries with a high-burden of tuberculosis (TB) are at a particular risk of contracting and developing the disease. In Sweden, new immigrants are routinely offered screening for the disease, yet very little is known about their beliefs about the disease which may affect healthcare-seeking behaviours. In this study we assessed recent immigrant students' knowledge of, and attitudes towards TB, and their relationship with the screening process. Data were collected over a one-year period through a survey questionnaire completed by 268 immigrants consecutively registered at two Swedish-language schools in Umeå, Sweden. Participants originated from 133 different countries and their ages varied between 16-63 years. Descriptive and multivariate logistic regression analyses were then performed. Though most of them (72%) were screened, knowledge was in general poor with several misconceptions. The average knowledge score was 2.7 +/- 1.3 (SD), (maximum = 8). Only 40 (15 %) of the 268 respondents answered at least half of the 51 knowledge items correctly. The average attitude score was 5.1 +/- 3.3 (SD) (maximum = 12) which meant that most respondents held negative attitudes towards TB and diseased persons. Up to 67% lacked knowledge about sources of information while 71% requested information in their vernacular. Knowledge level was positively associated with having more than 12 years of education and being informed about TB before moving to Sweden. Attitude was positively associated with years of education and having heard about the Swedish Communicable Disease Act, but was negatively associated with being from the Middle East. Neither knowledge nor attitude were affected by health screening or exposure to TB information after immigration to Sweden. Though the majority had contact with Swedish health professionals through the screening process, knowledge about tuberculosis among these immigrants was low with several misconceptions and negative attitudes. Information may currently be inaccessible to most of these immigrants due to the language barrier and unfamiliarity with the Swedish healthcare system. If TB education was included as a component of screening programmes, ensuring that it was tailored to educational background, addressed misconceptions and access problems, it could well help improve TB control in these communities.


Efficacy of the argon beam coagulator alone in obtaining hemostasis after laparoscopic porcine heminephrectomy: a pilot study.
The argon beam coagulator (ABC) is used in combination with other hemostatic agents and suture renorrhaphy to obtain hemostasis after laparoscopic partial nephrectomy. We performed a pilot study evaluating the efficacy of the ABC-alone in obtaining hemostasis during laparoscopic heminephrectomy (LHN) in a porcine model. Eight pigs (4 small (30 kg-40 kg) and 4 large (70 kg-80 kg)), underwent bilateral LHN. Hemostasis then was obtained by using the ABC at 120W as a single modality. The collecting system was not repaired. The hilum was unclamped and the renal defect observed for 20 minutes with pneumoperitoneum pressure of 4 mmHg. The animals were survived for 24 hours at which time they were sacrificed and necropsy performed. All small pigs underwent LHN successfully. Mean pre- and post-op Hgb were 11.2 g/dl and 9.8 g/dl, respectively (p=0.12). In one of the animals, ABC at 150W was required to obtain hemostasis. All but one of the large pigs underwent LHN successfully. One of the animals had continuous bleeding despite ABC after right LHN and a completion nephrectomy was performed. Pre and postoperative Hgb for the large pigs were 9.9 g/dl and 9.3 g/dl, respectively (p=0.24). The ABC-alone was successful in obtaining hemostasis in all but two of the renal units in both small and large pigs. The two hemostatic failures were noticeable immediately after hilar unclamping. Our data suggest that ABC-alone provides adequate hemostasis when applied to small-caliber vessels. Further long term studies are needed to fully evaluate the efficacy of the ABC.


Stigma, mental health, and resilience in an online sample of the US transgender population.
We assessed the association between minority stress, mental health, and potential ameliorating factors in a large, community-based, geographically diverse sample of the US transgender population. In 2003, we recruited through the Internet a sample of 1093 male-to-female and female-to-male transgender persons, stratified by gender. Participants completed an online survey that included standardized measures of mental health. Guided by the minority stress model, we evaluated associations between stigma and mental health and tested whether indicators of resilience (family support, peer support, identity pride) moderated these associations. Respondents had a high prevalence of clinical depression (44.1%), anxiety (33.2%), and somatization (27.5%). Social stigma was positively associated with psychological distress. Peer support (from other transgender people) moderated this relationship. We found few differences by gender identity. Our findings support the minority stress model. Prevention needs to confront social structures, norms, and attitudes that produce minority stress for gender-variant people; enhance peer support; and improve access to mental health and social services that affirm transgender identity and promote resilience.


Autophagy promotes triple negative breast cancer metastasis via YAP nuclear localization.
The triple-negative breast cancer (TNBC) subtype is the most aggressive form of invasive breast cancer. Although autophagy is critical to the progression of TNBC, the mechanism of autophagy in regulating the metastatic potential of TNBC still remains unclear. Recently, the effector of the Hippo signaling pathway yes-associated protein (YAP) was shown to promote autophagy. To investigate autophagy regulation in YAP signaling in the context of cancer metastasis, we performed profiling analysis of YAP signaling, YAP subcellular localization, autophagosome formation and cell invasiveness in TNBC cell lines (MDA-MB-231 and Hs 578T) versus estrogen receptor (ER) positive breast cancer cell line MCF7. Our results showed that YAP transcriptional and protein expression was significantly upregulated in TNBC. When we triggered autophagy response in TNBC, YAP translocated into the nucleus and the expression of YAP target gene ankyrin repeat domain 1 (ANKRD1) increased remarkably. The correlation between autophagy response and YAP expression in TNBC was confirmed at the single-cell level. Furthermore, the inhibition of YAP nuclear entry greatly impeded the migration and invasion of TNBC cells while it did not affect the mobility of ER positive breast cancer cells. Therefore, this research established the autophagy-YAP-metastasis axis in TNBC and sheds light on the application of targeting YAP for TNBC therapeutics.