Developing syndrome definitions based on consensus and current use.
Standardized surveillance syndromes do not exist but would facilitate sharing data among surveillance systems and comparing the accuracy of existing systems. The objective of this study was to create reference syndrome definitions from a consensus of investigators who currently have or are building syndromic surveillance systems. Clinical condition-syndrome pairs were catalogued for 10 surveillance systems across the United States and the representatives of these systems were brought together for a workshop to discuss consensus syndrome definitions. Consensus syndrome definitions were generated for the four syndromes monitored by the majority of the 10 participating surveillance systems: Respiratory, gastrointestinal, constitutional, and influenza-like illness (ILI). An important element in coming to consensus quickly was the development of a sensitive and specific definition for respiratory and gastrointestinal syndromes. After the workshop, the definitions were refined and supplemented with keywords and regular expressions, the keywords were mapped to standard vocabularies, and a web ontology language (OWL) ontology was created. The consensus definitions have not yet been validated through implementation. The consensus definitions provide an explicit description of the current state-of-the-art syndromes used in automated surveillance, which can subsequently be systematically evaluated against real data to improve the definitions. The method for creating consensus definitions could be applied to other domains that have diverse existing definitions.


Use of an in vitro biotinylation technique for determination of posttransfusion survival of fresh and stored autologous red blood cells in Thoroughbreds.
To evaluate N-hydroxysuccinimide (NHS)-biotin labeling of equine RBCs and determine posttransfusion survival of autologous equine RBCs stored in citrate phosphate dextrose adenine-1 (CPDA-1) for 0, 1, 14, and 28 days. 13 healthy adult Thoroughbreds. Serial dilutions of biotin and streptavidin-phycoerythrin (PE) were evaluated in vitro in blood collected from 3 horses. One horse was used to determine RBC distribution and recovery. Twelve horses were allocated to 4 groups for in vivo experiments in which blood was collected into CPDA-1. Blood was labeled with biotin and reinfused or stored at 4 degrees C for 1, 14, or 28 days prior to labeling with NHS-biotin and reinfusion. Posttransfusion blood samples were collected 15 minutes and 1, 2, 3, 5, 7, 14, 21, 28, and 35 days after reinfusion. Biotin-labeled RBCs were detected via flow cytometry by use of streptavidin-PE. Posttransfusion lifespan of RBCs and RBC half-life were determined. Optimal biotin concentration was 0.04 pg of biotin/RBC, and the optimal streptavidin-PE ratio was 1.2 microg of streptavidin-PE/1 x 10(6) RBCs. Posttransfusion lifespan of autologous RBCs was 99, 89, 66, and 59 days after storage for 0, 1, 14, and 28 days, respectively. Storage did not result in significant alterations in RBC lifespan. Mean posttransfusion RBC half-life was 50, 45, 33, and 29 days for 0, 1, 14, and 28 days of storage, respectively. Biotin can be used to label equine RBCs for RBC survival studies. Posttransfusion survival of equine autologous RBCs was greater than previously reported.


Anxiety symptomatology, sex and chronotype: The mediational effect of diurnal sleepiness.
Diurnal subjective sleepiness has been associated with a large number of negative outcomes, such as increased risk of accidents and development of mental disorders as depression and anxiety. However, the role of the diurnal subjective sleepiness as a mediator is poorly understood. The goal of the present study was to examine the role of diurnal subjective sleepiness as a mediator of the relationship between sex, chronotype and anxiety symptoms in healthy young adults. Four-hundred and sixty-seven healthy young adults (64.8% females, age range 18-32 years, mean 20.7, ±2.3) were evaluated with validated and widely used scales for the measurement of diurnal sleepiness, anxiety symptoms and morningness-eveningness preference. We have found that diurnal subjective sleepiness correlated with anxiety symptoms when evaluated both in the total sample and within chronotypes. This association was more important in females than in males (p < 0.0001). Regarding chronotype, only for morning-types, diurnal subjective sleepiness was a significant mediator of the relationship between sex and anxiety symptoms. This is the first study that examines the mediator role of diurnal subjective sleepiness in the known relationship between sex and anxiety symptoms, and adds new evidence about the effect of the chronotype on sleep problems and mental health. Although future work is required, our results have important implications for clinical settings and public health interventions.


Identification of a pea component stimulatory for heat-stressed putrefactive anaerobe 59-123 spores.
Pea extract contains a factor which improves recovery counts of heat-stressed putrefactive anaerobe spores in a complex medium up to threefold. The factor is heat-stable and nondialyzable. Most of the active principle is found in the precipitate which forms during storage of pea extract at 4 C. The precipitate disperses upon heating, is high in starch content, and retains activity after extraction with organic solvents and water. Treatment of pea extract with alpha-amylase results in complete destruction of the active principle. These observations indicate that starch is the factor in pea extract responsible for increased recovery counts of heat-stressed putrefactive anaerobe spores.


Hyperfractionated or accelerated radiotherapy for head and neck cancer.
Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival. We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998. We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality. We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.


Effects of reclassification from the TNM-6 into the TNM-7 staging system in bronchoplastic resection for non-small cell lung cancer.
In 2007, the International Association for the Study of Lung Cancer proposed changes to the sixth edition of the lung cancer stage classification system, which were adopted by the Union Internationale Contre le Cancer in 2009 (TNM-7). Using historic patient data, the effects of reclassification from the TNM-6 to the TNM-7 system were researched within a single institution. We retrospectively reclassified the pathological records of 145 patients who underwent bronchoplastic resection for non-small cell lung cancer between 1991 and 2004, by applying the new TNM-7 classification for lung cancer. A comparison between the previous and the new system was conducted. Out of 145 patients, 49 (33.8%) were reclassified into a new stage, 42 (85.7% of reclassified cases) being allocated to a lower and seven (14.3%) being assigned to a higher stage. Most of the patients switched from stage IIB to IIA (n=31, 63.3%). The application of the new TNM-7 staging system resulted in a more accurate stratification of five-year survival curves. The newly revised TNM classification for lung cancer appears to be superior in defining different prognostic groups for this cohort and should lead to an improvement in stage specific tumor therapy.


Adolescent smoking trajectories and nicotine dependence.
The present study correlates empirically constructed prospective adolescent smoking trajectories with indicators of nicotine dependence assessed in adolescence and in adulthood. Excluding individuals who reported no smoking during repeat assessment (nonadopters), we identified five smoking trajectory groups: experimenters (n=116, 48.5%), late increasers (n=39, 16.3%), early increasers (n=37, 15.5%), quitters (n=22, 9.2%), and persistent smokers (n=25, 10.5%). Higher frequency of nicotine dependence symptoms in adolescence occurred in the quitters and persistent smokers groups, who smoked at higher levels relative to the experimenters, late increasers, and early increasers groups, who reported a similar frequency of nicotine dependence symptoms and smoked at low levels. Lifetime nicotine dependence was assessed in adulthood in lifetime daily smokers using the Fagerström Test for Nicotine Dependence (FTND) and the Nicotine Dependence Scale (NDS). Lifetime FTND levels were similar across trajectory groups. Relative to experimenters, all remaining smoking trajectory groups had higher NDS levels that were similar to one another. These results suggest that higher levels of adolescent nicotine dependence were associated with heavier smoking trajectory groups, and that regardless of trajectory group membership, smoking more than a few cigarettes per week throughout adolescence resulted in similar levels of lifetime nicotine dependence as measured by the FTND and NDS.


A residue in the transmembrane segment 6 of domain I in insect and mammalian sodium channels regulate differential sensitivities to pyrethroid insecticides.
Voltage-gated sodium channels are critical for electrical signaling in the nervous system. Pyrethroid insecticides exert their toxic action by modifying the gating of sodium channels. A valine to methionine mutation in the transmembrane segment 6 of domain I (IS6) of sodium channels from tobacco budworms (Heliothis virescens) has been shown to alter channel gating and reduce insect sodium channel sensitivity to pyrethroids. A valine to leucine substitution was subsequently reported in pyrethroid-resistant bedbug populations. Intriguingly, pyrethroid-resistant mammalian sodium channels possess an isoleucine at the corresponding position. To determine whether different substitutions at this position alter channel gating and confer pyrethroid resistance, we made valine to methionine, isoleucine or leucine substitutions at the corresponding position, V409, in a cockroach sodium channel and examined the gating properties and pyrethroid sensitivity of the three mutants in Xenopus oocytes. All three mutations reduced the channel sensitivity to three pyrethroids (permethrin, cismethrin and deltamethrin). V409M, but not V409I or V409L, caused 6-7mV depolarizing shifts in the voltage dependences of both activation and inactivation. V409M and V409L slowed channel activation kinetics and accelerated open-state deactivation kinetics, but V409I did not. Furthermore, the substitution of isoleucine with valine, but not with methionine nor leucine, at the corresponding position in a rat skeletal muscle sodium channel, rNav1.4, enhanced channel sensitivity to deltamethrin. Collectively, our study highlights an important role of residues at 409 in regulating not only sodium channel gating, but also the differential sensitivities of insect and mammalian sodium channels to pyrethroids.


Cartilage matrix protein forms a type II collagen-independent filamentous network: analysis in primary cell cultures with a retrovirus expression system.
Cartilage matrix protein (CMP) is expressed specifically in mature cartilage and consists of two von Willebrand factor A domains (CMP-A1 and CMP-A2) that are separated by an epidermal growth factor-like domain, and a coiled-coil tail domain at the carboxyl terminal end. We have shown previously that CMP interacts with type II collagen-containing fibrils in cartilage. In this study, we describe a type II collagen-independent CMP filament and we analyze the structural requirement for the formation of this type of filament. Recombinant wild-type CMP and two mutant forms were expressed in chick primary cell cultures using a retrovirus expression system. In chondrocytes, the wild-type virally encoded CMP is able to form disulfide bonded trimers and to assemble into filaments. Filaments also form with CMP whose Cys455 and Cys457 in the tail domain were mutagenized to prevent interchain disulfide bond formation. Therefore, intermolecular disulfide bonds are not necessary for the assembly of CMP into filaments. Both the wild-type and the double cysteine mutant also form filaments in fibroblasts, indicating that chondrocyte-specific factors are not required for filament formation. A truncated form of CMP that consists only of the CMP-A2 domain and the tail domain can form trimers but fails to form filaments, indicating that the deleted CMP-A1 domain and/or the epidermal growth factor domain are necessary for filament assembly but not for trimer formation. Furthermore, the expression of the virally encoded truncated CMP in chondrocyte culture disrupts endogenous CMP filament formation. Together these data suggest a role for CMP in cartilage matrix assembly by forming filamentous networks that require participation and coordination of individual domains of CMP.


Acute secondhand smoke-induced pulmonary inflammation is diminished in RAGE knockout mice.
The receptor for advanced glycation end-products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in proinflammatory signaling, and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short-term secondhand smoke (SHS) exposure in RAGE knockout and control mice compared with identical animals exposed to room air only. Quantitative PCR, immunoblotting, and immunohistochemistry revealed elevated RAGE expression in controls after 4 wk of SHS exposure and an anticipated absence of RAGE expression in RAGE knockout mice regardless of smoke exposure. Ras activation, NF-κB activity, and cytokine elaboration were assessed to characterize the molecular basis of SHS-induced inflammation in the mouse lung. Furthermore, bronchoalveolar lavage fluid was procured from RAGE knockout and control animals for the assessment of inflammatory cells and molecules. As a general theme, inflammation coincident with leukocyte recruitment was induced by SHS exposure and significantly influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to SHS. However, ongoing research is still warranted to fully explain roles for RAGE and other receptors in cells coping with involuntary smoke exposure for prolonged periods of time.


Systematic literature review of templates for reporting prehospital major incident medical management.
To identify and describe the content of templates for reporting prehospital major incident medical management. Systematic literature review according to PRISMA guidelines. PubMed/MEDLINE, EMBASE, CINAHL, Scopus and Web of Knowledge. Grey literature was also searched. Templates published after 1 January 1990 and up to 19 March 2012. Non-English language literature, except Scandinavian; literature without an available abstract; and literature reporting only psychological aspects were excluded. The main database search identified 8497 articles, among which 8389 were excluded based on title and abstract. An additional 96 were excluded based on the full-text. The remaining 12 articles were included in the analysis. A total of 107 articles were identified in the grey literature and excluded. The reference lists for the included articles identified five additional articles. A relevant article published after completing the search was also included. In the 18 articles included in the study, 10 different templates or sets of data are described: 2 methodologies for assessing major incident responses, 3 templates intended for reporting from exercises, 2 guidelines for reporting in medical journals, 2 analyses of previous disasters and 1 Utstein-style template. More than one template exists for generating reports. The limitations of the existing templates involve internal and external validity, and none of them have been tested for feasibility in real-life incidents. The review is registered in PROSPERO (registration number: CRD42012002051).


Enabling Open Science for Health Research: Collaborative Informatics Environment for Learning on Health Outcomes (CIELO).
There is an emergent and intensive dialogue in the United States with regard to the accessibility, reproducibility, and rigor of health research. This discussion is also closely aligned with the need to identify sustainable ways to expand the national research enterprise and to generate actionable results that can be applied to improve the nation's health. The principles and practices of Open Science offer a promising path to address both goals by facilitating (1) increased transparency of data and methods, which promotes research reproducibility and rigor; and (2) cumulative efficiencies wherein research tools and the output of research are combined to accelerate the delivery of new knowledge in proximal domains, thereby resulting in greater productivity and a reduction in redundant research investments. AcademyHealth's Electronic Data Methods (EDM) Forum implemented a proof-of-concept open science platform for health research called the Collaborative Informatics Environment for Learning on Health Outcomes (CIELO). The EDM Forum conducted a user-centered design process to elucidate important and high-level requirements for creating and sustaining an open science paradigm. By implementing CIELO and engaging a variety of potential users in its public beta testing, the EDM Forum has been able to elucidate a broad range of stakeholder needs and requirements related to the use of an open science platform focused on health research in a variety of "real world" settings. Our initial design and development experience over the course of the CIELO project has provided the basis for a vigorous dialogue between stakeholder community members regarding the capabilities that will add the greatest value to an open science platform for the health research community. A number of important questions around user incentives, sustainability, and scalability will require further community dialogue and agreement.


[History and definition of sepsis--do we need new terminology?].
The history of sepsis demonstrates that despite current knowledge about its pathogenesis the definition of sepsis is more contested than ever. However, a definite terminology is necessary to define the entrance criteria for future clinical studies concerning patients with sepsis or septic shock. For this purpose, in 1991 a consensus conference was held in the US, but its recommendations have not found unequivocal acceptance. These recommendations and their historical background are presented and their consequences discussed.


Collaborative health literate depression care among predominantly Hispanic patients with coronary heart disease in safety net care.
To determine whether evidence-based socioculturally health literate-adapted collaborative depression care improves depression care, depressive symptoms, and quality of life among predominantly Hispanic patients with coronary heart disease. The 12-month trial included 97 patients with coronary heart disease (79% of eligible patients) who met the depression criteria assessed by the Patient Health Questionnaire-9. Patients were recruited from 3 safety net clinics and offered depression team care by a bilingual clinical social worker and community patient navigator, a consulting psychiatrist, and a primary care physician. The team provided problem-solving therapy (PST) or pharmacotherapy or both, telephone symptom monitoring and behavioral activation, and patient resource navigation support. Recruited patients were given patient and family member health literacy-adapted educational and community resource materials in Spanish or English. Overall, depression treatment was 74% (PST, 55%; PST plus antidepressant medications, 18%; and antidepressant medications alone, 2%). Nearly half of the patients showed a 50% reduction of the Symptom Checklist-20 (49% at 6 mo and 48% at 12 mo) and of Patient Health Questionnaire-9 score with 47% of patients at 6 months and 43% at 12 months. The 50% improvement in Patient Health Questionnaire and Symptom Checklist-20 score reduction did not vary significantly between patients who received PST or antidepressant only or those who received PST plus antidepressant. The quality of life Short-Form Health Survey SF-12, the Minnesota Living with Heart Failure questionnaire, and the Sheehan Disability Scale outcomes also improved significantly. Socioculturally literacy-adapted collaborative depression care was accepted by patients with coronary heart disease and improved depression care and symptoms, quality of life, and functional outcomes among predominantly Hispanic patients with heart disease.


Sex steroids: beyond conventional dimorphism.
Sexual dimorphism is a characteristic of a large number of species, ranging from lower invertebrates to mammals and, last but not least, humans. Recognition of the various factors regulating sexual dimorphism initial establishment (i.e. sex determination and differentiation) and subsequent life-long adaptation to distinct functional and behavioural patterns has remained a hot topic for several decades. As our understanding of the various molecular pathways involved in this process increases, the significant role of sex steroids becomes more evident. At the same time, the recognition of new sites of steroid production (e.g. parts of the brain) and aromatization, as well as new target cells (owing to the proposed presence of additional receptors to those classically considered as primary steroid receptors) has lead to the need to revisit their spectrum of actions within a novel, multifactorial context. Thus, anthropology and medicine are presented with the challenge to unravel a major mystery, i.e. that of sexual orientation and differentiation and its potential contribution in human evolution and civilization development, taking advantage of the high-tech research tools provided by modern biotechnology. This short review summarizes the basic principles of sex determination and sex steroid function as they have been classically described in the literature and then proceeds to present examples of how modern research methods have started to offer a new insight on the more subtle details of this process, stressing that it is extending to virtually every single part and system of the body.


Eyeballing: the use of visual appearance to diagnose 'sick'.
Prior studies suggest that clinicians can categorise patients in an emergency room as 'sick' or 'not sick' using rapid visual assessment. The rapid nature of these decisions suggests clinicians are relying on pattern recognition or System 1 processing; however, this has not been studied experimentally. In this study, we explore the accuracy of these decisions using patient disposition (discharge, admission to ward or admission to critical care) as an objective outcome, and collect evidence to argue for the use of System 1 processing in the 'sick' or 'not sick' decision process. Fourteen practising emergency physicians reviewed 25 videos of patients presenting to the emergency room. They were asked to predict patient disposition (discharge, admission to ward or admission to critical care) and estimate whether they were 'sick' or 'not sick' using a continuous slider on a 'sick' scale from 'not sick' (0) to 'sick' (100). We collected decision time and asked physicians to identify how they came to the decision using a continuous slider on a 'system processing' scale from 'knew immediately' (0) to 'deliberated intently' (1). Inter-rater reliability judging 'sick' was computed as an intraclass correlation coefficient (ICC) of 0.54. Agreement among physicians in predicting disposition was 68% with ICC of 0.44, and accuracy at predicting disposition was 55%. Physicians made their decision in an average of 10 - 11 seconds and rated 70% of their decisions as < 0.5 on the scale from 'knew immediately' (0) to 'deliberated intently' (1). Experienced emergency physicians are able to visually assess patients rapidly and predict disposition in a very short time, albeit with fair reliability and lower accuracy than reported previously. Subjectively, they reported that the majority of decisions were on the side of 'knew immediately', consistent with the application of System 1 processing.


[Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease].
In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.


The Effects of Four Weeks of Chiropractic Spinal Adjustments on Blood Biomarkers in Adults with Chronic Stroke: Secondary Outcomes of a Randomized Controlled Trial.
Certain blood biomarkers are associated with neural protection and neural plasticity in healthy people and individuals with prior brain injury. To date, no studies have evaluated the effects chiropractic care on serum brain-derived neurotrophic factor (BDNF), insulin-like growth factor-II (IGF-II) and glial cell-derived neurotrophic factor (GDNF) in people with stroke. This manuscript reports pre-specified, exploratory, secondary outcomes from a previously completed parallel group randomized controlled trial. We evaluated differences between four weeks of chiropractic spinal adjustments combined with the usual physical therapy (chiro + PT) and sham chiropractic with physical therapy (sham + PT) on resting serum BDNF, IGF-II and GDNF in 63 adults with chronic stroke. Blood samples were assessed at baseline, four weeks (post-intervention), and eight weeks (follow-up). Data were analyzed using a linear multivariate mixed effects model. Within both groups there was a significant decrease in the mean log-concentration of BDNF and IGF-II at each follow-up, and significant increase log-concentration of GDNF at eight-weeks' follow-up. However, no significant between-group differences in any of the blood biomarkers at each time-point were found. Further research is required to explore which factors influence changes in serum BDNF, IGF-II and GDNF following chiropractic spinal adjustments and physical therapy.


The influence of patient's motivation on reported pain during orthodontic treatment.
Patients usually experience pain during orthodontic treatment. This fact can affect cooperation and the development of treatment. Reporting pain during treatment seems to be influenced by emotional aspects such as the patient's motivation. To assess the relationship between patient's motivation and the intensity of reported pain during two stages of treatment. Twenty males (11-37 years old) answered a questionnaire divided into five categories regarding their motivation towards treatment. The subjects were studied for 14 days (7 days with bonded brackets and 7 days with the initial arch inserted) and the intensity of pain was evaluated on a daily basis. All the issues, including the intensity of pain, were measured through the visual analog scale (VAS). The VAS-associated questionnaire proved to have good temporal reliability and reasonable internal consistency, being that the "perceived severity" domain had the greatest, although not significant (p = 0.196) correlation with pain intensity. Only the question asking the patients if they thought that their teeth were too uneven showed a positive correlation with pain intensity (p = 0.048). The results seem to indicate that the five categories related to treatment motivation cannot be used to predict discomfort during treatment. In addition, patients who think their teeth are too uneven may experience more severe pain due to greater force application after insertion of the initial arch.


Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial.
The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.


True incidence of all complications following immediate and delayed breast reconstruction.
Improved self-image and psychological well-being after breast reconstruction are well documented. To determine methods that optimized results with minimal morbidity, the authors examined their results and complications based on reconstruction method and timing. The authors reviewed all breast reconstructions after mastectomy for breast cancer performed under the supervision of a single surgeon over a 6-year period at a tertiary referral center. Reconstruction method and timing, patient characteristics, and complication rates were reviewed. Reconstruction was performed on 240 consecutive women (94 bilateral and 146 unilateral; 334 total reconstructions). Reconstruction timing was evenly split between immediate (n = 167) and delayed (n = 167). Autologous tissue (n = 192) was more common than tissue expander/implant reconstruction (n = 142), and the free deep inferior epigastric perforator was the most common free flap (n = 124). The authors found no difference in the complication incidence with autologous reconstruction, whether performed immediately or delayed. However, there was a significantly higher complication rate following immediate placement of a tissue expander when compared with delayed reconstruction (p = 0.008). Capsular contracture was a significantly more common late complication following immediate (40.4 percent) versus delayed (17.0 percent) reconstruction (p < 0.001; odds ratio, 5.2; 95 percent confidence interval, 2.3 to 11.6). Autologous reconstruction can be performed immediately or delayed, with optimal aesthetic outcome and low flap loss risk. However, the overall complication and capsular contracture incidence following immediate tissue expander/implant reconstruction was much higher than when performed delayed. Thus, tissue expander placement at the time of mastectomy may not necessarily save the patient an extra operation and may compromise the final aesthetic outcome.


MOB1, an essential yeast gene required for completion of mitosis and maintenance of ploidy.
Mob1p is an essential Saccharomyces cerevisiae protein, identified from a two-hybrid screen, that binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Mob1p contains no known structural motifs; however MOB1 is a member of a conserved gene family and shares sequence similarity with a nonessential yeast gene, MOB2. Mob1p is a phosphoprotein in vivo and a substrate for the Mps1p kinase in vitro. Conditional alleles of MOB1 cause a late nuclear division arrest at restrictive temperature. MOB1 exhibits genetic interaction with three other yeast genes required for the completion of mitosis, LTE1, CDC5, and CDC15 (the latter two encode essential protein kinases). Most haploid mutant mob1 strains also display a complete increase in ploidy at permissive temperature. The mechanism for the increase in ploidy may occur through MPS1 function. One mob1 strain, which maintains stable haploidy at both permissive and restrictive temperature, diploidizes at permissive temperature when combined with the mps1-1 mutation. Strains containing mob2Delta also display a complete increase in ploidy when combined with the mps1-1 mutation. Perhaps in addition to, or as part of, its essential function in late mitosis, MOB1 is required for a cell cycle reset function necessary for the initiation of the spindle pole body duplication.


Immunogenetics of nasopharyngeal carcinoma--position in 1980.
The HLA profile of 313 newly diagnosed Chinese NPC patients was compared to that of 330 normal Chinese subjects. A2 Bw46 and Aw19/B B17 were associated with increase risks of developing NPC whereas A11 was associated with a decreased risk. A2 Bw46 was confined to older onset patients whereas Aw19/B B17 was associated with NPC patients of all ages but particularly with younger patients. The Aw19/B B17 haplotypes was also associated with poor survival. A DR blank was strongly associated with NPC giving a relative risk of 26.5. In Malay NPC the HLA associations were Aw19/B B17 and A9 B18 and in Kadazan NPC, the association was with A9. Possible mechanisms of the HLA association were discussed.


Generalized second law in cosmology from causal boundary entropy
A classical and quantum mechanical generalized second law of thermodynamics in cosmology implies constraints on the effective equation of state of the universe in the form of energy conditions, obeyed by many known cosmological solutions, forbids certain cosmological singularities, and is compatible with entropy bounds. This second law is based on the conjecture that causal boundaries and not only event horizons have geometric entropies proportional to their area. In string cosmology the second law provides new information about nonsingular solutions.


A cancer associated somatic mutation in LC3B attenuates its binding to E1-like ATG7 protein and subsequent lipidation.
Macroautophagy/autophagy is a conserved catabolic process that maintains cellular homeostasis under basal growth and stress conditions. In cancer, autophagy can either prevent or promote tumor growth, at early or advanced stages, respectively. We screened public databases to identify autophagy-related somatic mutations in cancer, using a computational approach to identify cancer mutational target sites, employing exact statistics. The top significant hit was a missense mutation (Y113C) in the MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta) protein, which occurred at a significant frequency in cancer, and was detected in early stages in primary tumors of patients with known tumor lineage. The mutation reduced the formation of GFP-LC3B puncta and attenuated LC3B lipidation during Torin1-induced autophagy. Its effect on the direct physical interaction of LC3B with each of the 4 proteins that control its maturation or lipidation was tested by applying a protein-fragment complementation assay and co-immunoprecipitation experiments. Interactions with ATG4A and ATG4B proteases were reduced, yet without perturbing the cleavage of mutant LC3B. Most importantly, the mutation significantly reduced the interaction with the E1-like enzyme ATG7, but not the direct interaction with the E2-like enzyme ATG3, suggesting a selective perturbation in the binding of LC3B to some of its partner proteins. Structure analysis and molecular dynamics simulations of LC3B protein and its mutant suggest that the mutation changes the conformation of a loop that has several contact sites with ATG4B and the ATG7 homodimer. We suggest that this loss-of-function mutation, which attenuates autophagy, may promote early stages of cancer development.


The prevalence of Tourette syndrome in a mainstream school population.
The aim of this study was to ascertain accurately the prevalence of Tourette syndrome (TS) in a mainstream school population. All year 9 pupils (aged 13 to 14 years) in a mainstream secondary school were investigated using a two-stage procedure. Standardized questionnaires were completed by parents, teachers, and pupils. Class observations were also carried out to identify tics. Those pupils identified as having tics underwent a semistructured interview to determine whether they had TS according to DSM-III-R criteria. Data were available from at least one source (parent, teacher, or self-reports) on 166 of the 167 pupils in the year. Five subjects were identified as having TS according to DSM-III-R criteria, yielding a prevalence estimate of 299 per 10,000 pupils in this age group. The results of this study suggest that TS in the community as a whole is more common and milder than those prevalence estimates and descriptions of the disorder based on TS encountered in secondary or tertiary health-care service settings.


Metabolic Labeling of Pseudaminic Acid-Containing Glycans on Bacterial Surfaces.
The rise in antibiotic-resistant bacteria is causing worldwide concerns. The urgent need for new antibacterial drugs calls for new thinking and strategies to explore novel, narrow-spectrum, and pathogen-specific antibacterial targets. Legionaminic acid (Leg) and pseudaminic acid (Pse) are nonulosonic acid carbohydrates with structural similarity to eukaryotic sialic acid, and are distributed in numerous pathogenic Gram-negative bacteria as components of cell surface-associated glycans. They are involved in the host interaction, pathogenicity, antiphage defense mechanism, and immune escape mechanism. To further explore their biological significance, we developed a synthesis of 2-acetamido-4-azidoacetamido-2,4,6-trideoxy-l-altrose (Alt-4NAz) and 2-azidoacetamido-4-acetamido-2,4,6-trideoxy-l-altrose (Alt-2NAz), among which Alt-4NAz served as an effective chemical reporter to realize bacterial Pse metabolic labeling. The effectiveness of this chemical reporter has been demonstrated in Pseudomonas aeruginosa, Vibrio vulnificus, and Acinetobacter baumannii strains. Expectedly, this strategy can provide a useful assay to detect phenotypic presence of Pse biosynthesis and screen for agents targeting this pathway.


Receiver operating characteristic analysis of age-related changes in lineup performance.
In the basic face memory literature, support has been found for the late maturation hypothesis, which holds that face recognition ability is not fully developed until at least adolescence. Support for the late maturation hypothesis in the criminal lineup identification literature, however, has been equivocal because of the analytic approach that has been used to examine age-related changes in identification performance. Recently, receiver operator characteristic (ROC) analysis was applied for the first time in the adult eyewitness memory literature to examine whether memory sensitivity differs across different types of lineup tests. ROC analysis allows for the separation of memory sensitivity from response bias in the analysis of recognition data. Here, we have made the first ROC-based comparison of adults' and children's (5- and 6-year-olds and 9- and 10-year-olds) memory performance on lineups by reanalyzing data from Humphries, Holliday, and Flowe (2012). In line with the late maturation hypothesis, memory sensitivity was significantly greater for adults compared with young children. Memory sensitivity for older children was similar to that for adults. The results indicate that the late maturation hypothesis can be generalized to account for age-related performance differences on an eyewitness memory task. The implications for developmental eyewitness memory research are discussed.


In vivo gene delivery to synovium by lentiviral vectors.
The delivery of anti-arthritic genes to the synovial lining of joints is being explored as a strategy for the treatment of rheumatoid arthritis. In this study, we have investigated the use of VSV-G pseudotyped, HIV-1-based lentiviral vectors for gene delivery to articular tissues. Recombinant lentivirus containing a beta-galactosidase/neomycin resistance fusion gene under control of the elongation factor (EF) 1alpha promoter efficiently transduced human and rat synoviocytes and chondrocytes in cell culture. When directly injected into the knees of rats, this vector transduced synovial lining cells, but not other articular tissues such as cartilage. We also constructed a lentiviral vector containing the human interleukin-1 receptor antagonist (IL1RA) cDNA and examined transgene expression in vitro and in vivo following injection into the knee joints of rats. In immunocompetent animals, intra-articular IL1RA expression was high and persisted, at a sharply declining rate, for approximately 20 days. In immunocompromised rats, however, lentivirus-mediated intra-articular expression of human IL1RA was found to persist for at least 6 weeks. Extra-articular expression of the transgene was minimal. These results indicate that lentiviral vectors are capable of efficient in vivo gene transfer to synovium and merit further investigation as a means of providing long-term expression for gene-based treatments of arthritis.


[Morphology and contrast enhancement of ductal carcinoma in situ in dynamic 1.0 T MR mammography].
The detectability with magnetic resonance mammography (MR-M) of non-invasive ductal carcinoma in situ (DCIS), its morphology, and patterns of contrast enhancement were studied. A total of 849 MR-M examinations were performed in 741 patients using a dynamic, contrast-enhanced FLASH 3D sequence at 1.0 T. Surgical breast biopsies were obtained in 332 cases. Histological work-up confirmed 164 carcinomas, including 20 DCIS. Of 20 DCIS, 14 were correctly diagnosed by MR-M on the basis of focal increase of signal intensity. In two cases (10%), no increase of signal intensity was observed. In another three cases (15%), multifocal enhancement lead to a false-negative diagnosis. In one case (5%), DCIS was a random finding in a patient diagnosed and treated for adjacent phylloides tumour. The sensitivity of MR-M was 70%. 4 (20%) of the DCIS did not show microcalcifications at conventional mammography and were only detected at MR-M. The sensitivity of conventional mammography also amounted to 70%. However, the combination of both imaging methods increased sensitivity to 90%. Ductal carcinoma in situ is not reliably detectable by MR-mammography alone due to lack of a uniform pattern of enhancement.


Quantifying Upper Airway Changes Following Mandibular Orthognathic Surgery.
The aim of this study was to quantify upper airway changes following mandibular orthognathic surgery. Treatment records of 50 patients who underwent mandibular orthognathic surgery were divided into 2 groups, that is, Group 1: Cases treated with Mandibular Advancement Surgery and Group 2: Cases treated with Mandibular Setback Surgery with 25 patients in each group. The Lateral Cephalogram and Acoustic Pharyngometry records of both groups were studied at T0 (01 week before surgery) and T1 (01 year postsurgery) for changes in linear airway measurements (Nasopharyngeal Airway Space - NAS, Superior Airway Space - SAS, Posterior Airway Space - PAS and Hypopharyngeal Airway Space (HAS)), hyoid bone position (Mandibular Plane Hyoid distance), mean area and mean volume. The percentage change and change in these parameters per millimeter advancement or setback of mandible at T1 was calculated. A significant increase in linear airway parameters (SAS and PAS); decrease in hyoid distance; and increase in volume and area of upper airway was observed at T1 in Group 1 and reverse was observed in Group 2. The change in airway parameters (SAS, PAS, mean volume and area) was more significant in Group 1 as compared to Group 2. In the current airway centric approach, meticulous assessment and prediction of long-term airway changes post surgery should be an integral part of ortho-surgical diagnosis and treatment planning and suitable modifications in the treatment plan must be made to cater for any potential adverse effects on airway.


Simultaneous measurement of gastric emptying, small bowel residence and colonic filling of a solid meal by the use of the gamma camera.
A method for determining the profiles of gastric emptying, small intestinal residence, and colonic filling of a solid test meal, labelled with 250 microCi 99mTechnetium sulphur colloid has been evaluated in nine healthy volunteers and six patients with a disturbance in bowel habit. Mean small bowel transit time was determined by deconvolving the rate of colonic filling with the rate of gastric emptying. In normal subjects, the stomach appeared to empty exponentially with a half time of 1.2 +/- 0.3 hours (mean +/- SD). Food reached the colon by 2.8 +/- 1.5 hours. The mean small bowel transit time was 4.0 +/- 1.4 hours. In most normal subjects, the colon appeared to fill in a linear fashion with approximately 16% food residues entering every hour, and the profile of colonic filling in normal subjects was similar to the profile of ileal emptying observed after feeding a similar radiolabelled solid meal to 14 patients equipped with terminal ileostomies. There was a highly significant correlation between the onset of breath hydrogen excretion and the appearance of radioactivity over the caecum (r = 0.88, p less than 0.01), though in one third of subjects the increase in caecal radioactivity preceded the rise in breath hydrogen concentration by more than 20 minutes. There was also a highly significant correlation between the mean transit time and values for colonic filling but not values for gastric emptying. Patients with irritable bowel syndrome who had diarrhoea tended towards short small bowel transit and early colonic filling, whereas patients who have constipation tended towards long small bowel transit and delayed colonic filling. This method offers a novel means of assessing small bowel transit time, small bowel residence and the profile of colonic filling in man.


[Consideration of home care for patients with advanced cancer--surgeon's viewpoint].
There is a tendency to consider that home care is promoted as an alternative to reduce the mean duration of hospital stay. Home care must be carried out according to the wish of both the patient himself and his family. At present, home care has reached a high levels, so that it can be carried out safely. As a surgeon, I think that we must make use of the system of home care established to allow patients to live at home when they wish to do so, and I want to let them stay in the hospital if they prefer so.


The surgical pathology laboratory in Mwanza, Tanzania: a survey on the reproducibility of diagnoses after the first years of autonomous activity.
In 2000, an Italian non-governmental organisation (NGO) began a 9-year project to establish a surgical pathology laboratory at the Bugando Medical Centre (BMC) in Mwanza, Tanzania, a country with a low Human Development Index (HDI), and as of 2009, the laboratory was operating autonomously. The present survey aims to evaluate the reproducibility of histological and cytological diagnoses assigned in the laboratory's early years of autonomous activity. We selected a random sample of 196 histological and cytological diagnoses issued in 2010-2011 at the BMC surgical pathology laboratory. The corresponding samples were sent to Italy for review by Italian senior pathologists, who were blinded to the local results. Samples were classified into four diagnostic categories: malignant, benign, inflammatory, and suspicious. The two-observer kappa-statistic for categorised (qualitative) data was then calculated to measure diagnostic concordance between the local Tanzanian pathologists and Italian senior pathologists. The k-Cohen was calculated for concordance in the overall study sample. Concordance and discordance rates were also stratified by subset: general adult, paediatric/adolescent, and lymphoproliferative histopathological diagnoses; fluid and fine needle aspiration (FNA) cytological diagnoses; and PAP tests. Discordance was also categorised by the corresponding hypothetical clinical implications: high, intermediate, and not significant. Overall concordance was 85.2% (167 of 196 diagnoses), with a k-Cohen of 0.7691 (P = 0.0000). Very high concordance was observed in the subsets of adult general pathological diagnoses (90%) and paediatric/adolescent pathological diagnoses (91.18%). Concordance in the subset of PAP tests was 75%, and for fluid/FNA cytological diagnoses it was 56.52%. Concordance among 12 histological subtypes of lymphoma was 75.86%, with substantial discordance observed in the diagnosis of Burkitt lymphoma (five cases diagnosed by Italian pathologists versus 2 by local pathologists). The overall proportion of discordance with high hypothetical clinical implications was 6.1% (12 diagnoses). This blind review of diagnoses assigned in Tanzania, a country with low HDI, and in Italy, a country with a very high HDI, seemed to be a sensitive and effective method to identify areas of potential error and may represent a reference point for future, more detailed quality control processes or audits of surgical pathology services located in limited-resource regions.


Using high-frequency phosphorus monitoring for water quality management: a case study of the upper River Itchen, UK.
Increased concentrations of phosphorus (P) in riverine systems lead to eutrophication and can contribute to other environmental effects. Chalk rivers are known to be particularly sensitive to elevated P levels. We used high-frequency (daily) automatic water sampling at five distinct locations in the upper River Itchen (Hampshire, UK) between May 2016 and June 2017 to identify the main P species (including filterable reactive phosphorus, total filterable phosphorus, total phosphorus and total particulate phosphorus) present and how these varied temporally. Our filterable reactive phosphorus (considered the biologically available fraction) data were compared with the available Environment Agency total reactive phosphorus (TRP) values over the same sampling period. Over the trial, the profiles of the P fractions were complex; the major fraction was total particulate phosphorus with the mean percentage value ranging between 69 and 82% of the total P present. Sources were likely to be attributable to wash off from agricultural activities. At all sites, the FRP and Environment Agency TRP mean concentrations over the study were comparable. However, there were a number of extended time periods (1 to 2 weeks) where the mean FRP concentration (e.g. 0.62 mg L-1) exceeded the existing regulatory values (giving a poor ecological status) for this type of river. Often, these exceedances were missed by the limited regulatory monitoring procedures undertaken by the Environment Agency. There is evidence that these spikes of elevated concentrations of P may have a biological impact on benthic invertebrate (e.g. blue-winged olive mayfly) communities that exist in these ecologically sensitive chalk streams. Further research is required to assess the ecological impact of P and how this might have implications for the development of future environmental regulations.


Depressive Symptoms in Recipients of Home- and Community-Based Services in the United States: Are Older Adults Receiving the Care They Need?
To understand unmet depression needs of older adults, the current study investigates depressive symptoms, psychiatric treatment, and home- and community-based service (HCBS) use in a nationally representative sample of older adults in the United States. Participants included 5,582 adults aged 60 and over from the 2010-2012 waves of the nationally representative Health and Retirement Study. Weighted bivariate analyses were used to examine the frequency of depressive symptoms (Center for Epidemiologic Studies Depression Scale) and psychiatric treatment among HCBS recipients compared with non-HCBS recipients. Weighted logistic regression models were used to evaluate the effect of depressive symptoms on HCBS use. HCBS recipients had a higher frequency of depressive symptoms compared with nonrecipients (27.5% versus 10.4%, respectively). In particular, transportation service recipients had the highest frequency of depressive symptoms (37.5%). HCBS recipients with depressive symptoms were no more likely than nonrecipients to receive psychiatric services. Depressive symptoms were associated with HCBS use, above and beyond sociodemographic and health risk factors. Depressive symptoms are more frequent among HCBS recipients compared with nonrecipients; however, depressed HCBS recipients are no more likely to receive psychiatric services, suggesting unmet depression needs. HCBS may be a key setting for depression detection and delivery of mental health interventions.


Reflex control of human jaw muscles.
The aim of this review is to discuss what is known about the reflex control of the human masticatory system and to propose a method for standardized investigation. Literature regarding the current knowledge of activation of jaw muscles, receptors involved in the feedback control, and reflex pathways is discussed. The reflexes are discussed under the headings of the stimulation conditions. This was deliberately done to remind the reader that under each stimulation condition, several receptor systems are activated, and that it is not yet possible to stimulate only one afferent system in isolation in human mastication experiments. To achieve a method for uniform investigation, we need to set a method for stimulation of the afferent pathway under study with minimal simultaneous activation of other receptor systems. This stimulation should also be done in an efficient and reproducible way. To substantiate our conviction to standardize the stimulus type and parameters, we discuss the advantages and disadvantages of mechanical and electrical stimuli. For mechanical stimulus to be delivered in a reproducible way, the following precautions are suggested: The stimulus delivery system (often a probe attached to a vibrator) should be brought into secure contact with the area of stimulation. To minimize the slack between the probe, the area to be stimulated should be taken up by the application of pre-load, and the delivered force should be recorded in series. Electrical stimulus has advantages in that it can be delivered in a reproducible way, though its physiological relevance can be questioned. It is also necessary to standardize the method for recording and analyzing the responses of the motoneurons to the stimulation. For that, a new technique is introduced, and its advantages over the currently used methods are discussed. The new method can illustrate the synaptic potential that is induced in the motoneurons without the errors that are unavoidable in the current techniques. We believe that once stimulation, recording, and analysis methods are standardized, it will be possible to bring out the real "wiring diagram" that operates in conscious human subjects.


Physiological and Proteomic Analyses of Two Acanthus Species to Tidal Flooding Stress.
The mangrove plant Acanthus ilicifolius and its relative, Acanthus mollis, have been previously proved to possess diverse pharmacological effects. Therefore, evaluating the differentially expressed proteins of these species under tidal flooding stress is essential to fully exploit and benefit from their medicinal values. The roots of A. ilicifolius and A. mollis were exposed to 6 h of flooding stress per day for 10 days. The dry weight, hydrogen peroxide (H2O2) content, anatomical characteristics, carbon and energy levels, and two-dimensional electrophoresis coupled with MALDI-TOF/TOF MS technology were used to reveal the divergent flooding resistant strategies. A. ilicifolius performed better under tidal flooding stress, which was reflected in the integrity of the morphological structure, more efficient use of carbon and energy, and a higher percentage of up-regulated proteins associated with carbon and energy metabolism. A. mollis could not survive in flooding conditions for a long time, as revealed by disrupting cell structures of the roots, less efficient use of carbon and energy, and a higher percentage of down-regulated proteins associated with carbon and energy metabolism. Energy provision and flux balance played a role in the flooding tolerance of A. ilicifolius and A. mollis.


CYP46A1 functional promoter haplotypes decipher genetic susceptibility to Alzheimer's disease.
We here demonstrate that promoter polymorphisms rs8003602 and rs3783320 of cholesterol 24S-hydroxylase (CYP46A1) were significantly associated with Alzheimer's disease (AD) in Chinese subjects. Haplotype analyses showed that haplotype CG is the risk haplotype. Either single marker or haplotypic association was found only in the APOE ε4 negative group. The association was then replicated in an independent set of case-control samples in Mongolians. We also investigated the function of promoter haplotypes and found that luciferase expression for TA promoter construct exhibited significantly higher expression level than the risk CG promoter construct. This finding might indicate individuals bearing the CG haplotype are genetically more susceptible to AD compared to those with TA haplotype. Further, we found MYT1 could be the potential transcription factor binding to the significant promoter polymorphism and mediated gene transcriptional activity. In general, our results show that promoter haplotypes could significantly affect CYP46A1 gene transcription level possibly through interacting with certain transcription factors.


The Role of Nurses and Community Health Workers in Confronting Neglected Tropical Diseases in Sub-Saharan Africa: A Systematic Review.
Neglected tropical diseases produce an enormous burden on many of the poorest and most disenfranchised populations in sub-Saharan Africa. Similar to other developing areas throughout the world, this region's dearth of skilled health providers renders Western-style primary care efforts to address such diseases unrealistic. Consequently, many countries rely on their corps of nurses and community health workers to engage with underserved and hard-to-reach populations in order provide interventions against these maladies. This article attempts to cull together recent literature on the impact that nurses and community health workers have had on neglected tropical diseases. A review of the literature was conducted to assess the role nurses and community health workers play in the primary, secondary, and tertiary prevention of neglected tropical diseases in sub-Saharan Africa. Articles published between January 2005 and December 2015 were reviewed in order to capture the full scope of nurses' and community health workers' responsibilities for neglected tropical disease control within their respective countries' health systems. A total of 59 articles were identified that fit all inclusion criteria. Successful disease control requires deep and meaningful engagement with local communities. Expanding the role of nurses and community health workers will be required if sub-Saharan African countries are to meet neglected tropical disease treatment goals and eliminate the possibility future disease transmission. Horizontal or multidisease control programs can create complimentary interactions between their different control activities as well as reduce costs through improved program efficiencies-benefits that vertical programs are not able to attain.


Spray-dried microspheres containing ketoprofen formulated into capsules and tablets.
In this study, microspheres were prepared by a spray-drying technique using solutions of ketoprofen and two polymers, cellulose acetate butyrate (CAB) and hydroypropylmethylcellulose phthalate (HPMCP), in different weight ratios. Different total concentrations were used in the feed solutions: 3, 6 and 9% w/v. The spray-dried microparticles were characterized in terms of shape (SEM), size (light scattering method), production yield and encapsulation efficiency. They were formulated into capsules; tablets were prepared by direct compression of the microparticles mixed with maltose and, in some cases, hydroypropylmethylcellulose (HPMC). In vitro release studies were performed both at acidic and neutral pHs. The spray-drying process of solutions of ketoprofen with polymeric blends of cellulose derivatives leads to microparticles which, depending on their final formulation (capsules or tablets), can give a rapid or prolonged drug release. The formulations here described can be proposed for the oral administration of NSAIDs.


Localization of the Tn5 transposase promoter using the cycling reaction of RNA polymerase.
RNA polymerase is known to undergo a cycling process during initiation of transcription in vitro in which large amounts of small oligonucleotides are released. We have used this cycling reaction to determine the 5' end of the RNA synthesized from the outer ends of the Tn5 inverted repeats. By analyzing the size of the radiolabeled oligonucleotides synthesized using different labeled nucleoside triphosphates and in reactions deficient for a particular nucleoside triphosphate, the partial 5' sequence was obtained. This sequence was correlated with the DNA sequence of the region and an unambiguous origin for the mRNA was determined. The start site for the RNA, which is located at 97 base pairs from the outer ends of the inverted repeats, was confirmed by digesting gamma-32 P-ATP labeled full length (run off) transcripts with ribonuclease T1. The resulting gamma-labeled T1 generated oligonucleotide corresponded to the predicted size determined using the cycling reaction. With the knowledge of the RNA start site, the probable translation start sites for the protein(s) known to be required for Tn5 transposition can be predicted. Possible implications of the DNA sequence with respect to the regulation of the transposase are also discussed.


Contemporary Epidemiology of Chronic Liver Disease and Cirrhosis.
Accurate estimates for the contemporary burden of chronic liver disease (CLD) are vital for setting clinical, research, and policy priorities. We aimed to review the incidence, prevalence, and mortality of CLD and its resulting complications, including cirrhosis and hepatocellular carcinoma (HCC). We reviewed the published literature on the incidence, prevalence, trends of various etiologies of CLD and its resulting complications. In addition, we provided updated data from the Centers for Disease Control and Global Burden of Disease Study on the morbidity and mortality of CLD, cirrhosis, and hepatocellular carcinoma (HCC). Lastly, we assessed the strengths and weaknesses of available sources of data in hopes of providing important context to these national estimates of cirrhosis burden. An estimated 1.5 billion persons have CLD worldwide and the age-standardized incidence of CLD and cirrhosis is 20.7/100,000, a 13% increase since 2000. Similarly, cirrhosis prevalence and mortality has increased in recent years in the United States. The epidemiology of CLD is shifting, reflecting implementation of large-scale hepatitis B vaccination and hepatitis C treatment programs, the increasing prevalence of the metabolic syndrome, and increasing alcohol misuse. The global burden of CLD and cirrhosis is substantial. Although vaccination, screening, and antiviral treatment campaigns for hepatitis B and C have reduced the CLD burden in some parts of the world, concomitant increases in injection drug use, alcohol misuse, and metabolic syndrome threaten these trends. Ongoing efforts to address CLD-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes.


[A new program of therapeutic education for obese patients].
Obesity is a chronic disease which is increasing over the past thirty years. This disease is complex and its treatment is difficult and generally frustrating for the patients and the medical team because of a high risk of relapse. Indeed, a dietetic approach alone is most of the time not good enough to obtain a long-lasting weight loss; the few drugs on the market should also be prescribed as a part of a more global approach. A multidisciplinary approach with a long-standing follow-up including a cognitive-behavioral therapy coupled to a diet and physical activity is mandatory to avoid any weight regain. We propose a new multidisciplinary program of two years with in hospital-stay and ambulatory follow-up which is showing some promising results (90% of success at one year).


Crossed categorization in common ingroup contexts.
In three experiments, the authors tested the hypothesis that a common ingroup context would moderate evaluations of crossed category targets. In Experiment 1, the typical additive pattern of evaluation across artificial crossed category groups became a social inclusion pattern in a common ingroup context. In Experiment 2, the authors manipulated the importance of real crossed category targets. When the crossed groups were of low importance, the effects of imposing a common ingroup replicated those observed in Experiment 1. For important crossed groups, however, the additive pattern remained. In Experiment 3, the authors measured perceived importance of the crossed groups to social identity prior to introducing a common ingroup context. The effects of a common categorization on evaluations were again moderated by perceived importance. These findings are discussed in the context of integrating crossed categorization and common ingroup identity models of multiple categorization.


Dose dependent kinetics of carbamazepine in the monkey.
The blood concentration-time curve of carbamazepine in monkeys following intravenous infusion of the drug at two different levels was determined using a specific gas liquid chromatographic assaymconcentration values measured over a two and one-half decade concentration range during zero order infusion as well as the decay portion of the curve for both doses were computer fit using a nonlinear least-squares program and found to follow Michaelis-Menten kinetics. There was little change found in the volume of distribution for carbamazepine from monkey to monkey, however, marked differences were noted in the metabolic rate constants.


The marker choice: Unexpected resolving power of an unexplored CO1 region for layered DNA barcoding approaches.
The potential of DNA barcoding approaches to identify single species and characterize species compositions strongly depends on the marker choice. The prominent "Folmer region", a 648 basepair fragment at the 5' end of the mitochondrial CO1 gene, has been traditionally applied as a universal DNA barcoding region for metazoans. In order to find a suitable marker for biomonitoring odonates (dragonflies and damselflies), we here explore a new region of the CO1 gene (CO1B) for DNA barcoding in 51 populations of 23 dragonfly and damselfly species. We compare the "Folmer region", the mitochondrial ND1 gene (NADH dehydrogenase 1) and the new CO1 region with regard to (i) speed and reproducibility of sequence generation, (ii) levels of homoplasy and (iii) numbers of diagnostic characters for discriminating closely related sister taxa and populations. The performances of the gene regions regarding these criteria were quite different. Both, the amplification of CO1B and ND1 was highly reproducible and CO1B showed the highest potential for discriminating sister taxa at different taxonomic levels. In contrast, the amplification of the "Folmer region" using the universal primers was difficult and the third codon positions of this fragment have experienced nucleotide substitution saturation. Most important, exploring this new barcode region of the CO1 gene identified a higher discriminating power between closely related sister taxa. Together with the design of layered barcode approaches adapted to the specific taxonomic "environment", this new marker will further enhance the discrimination power at the species level.


Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh most common in women. This cancer varies widely in incidence throughout the world, with rising incidence in Egypt. HCC is considered the second most frequent cause of cancer incidence and mortality among men in Egypt. This study aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase in order to evaluate their role as oxidative status markers in HCC development and progression. For this purpose, serum levels of these parameters were assessed in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects as a control group. In the present study, glutathione reductase activity showed a significant increase in HCC as compared to the control group (P= 0.019). On the other hand, no significant difference was observed between the cirrhotic and HCC patients (P= 0.492). Serum NO was significantly higher in patients with HCC than in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1 μmol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker for HCC. The simultaneous determination of serum nitric oxide and AFP gave significant improvement in the detection of HCC patients compared to that of AFP alone.


Older People's Use and Nonuse of the Internet in Sweden.
The use of the internet has considerably increased over recent years, and the importance of internet use has also grown as services have gone online. Sweden is largely an information society like other countries with high reported use amongst European countries. In line with digitalization development, society is also changing, and many activities and services today take place on the internet. This development could potentially lead to those older persons who do not use the internet or do not follow the development of services on the internet finding it difficult to take part in information and activities that no longer occur in the physical world. This has led to a digital divide between groups, where the older generations (60+), in particular, have been affected. In a large study of Sweden's adult population in 2019, 95 percent of the overall population was said to be internet users, and the corresponding number for users over 66 years of age was 84%. This study shows that the numbers reported about older peoples' internet use, most likely, are vastly overestimated and that real use is significantly lower, especially among the oldest age groups. We report that 62.4% of the study subjects are internet users and that this number most likely also is an overestimation. When looking at nonresponders to the questionnaire, we find that they display characteristics generally attributed to non-use, such as lower education, lower household economy, and lower cognitive functioning.


Degradation of vincristine by myeloperoxidase and hypochlorous acid in children with acute lymphoblastic leukemia.
Vincristine (VCR) is an effective drug against acute lymphoblastic leukemia (ALL), many solid tumors, but not acute myeloid leukemia. It has been hypothesized that resistance of myeloblasts to VCR is related to myeloperoxidase (MPO) and production of hypochlorous acid (HOCl). We investigated the relationship between VCR degradation and MPO expression and serum HOCl concentrations in pediatric patients with ALL, lymphoma and solid tumors. We studied the sera from 43 children, of which 23 were newly diagnosed and as yet untreated cancer patients, 10 on chemotherapy and 10 healthy control subjects. Patients' sera were incubated with VCR alone or in the presence of taurine (T) or acetaminophen (APAP) and post-incubation VCR and HOCL concentrations were measured. Significant correlations between serum MPO expression, HOCl concentrations and VCR degradation were seen. In the chemotherapy group, MPO-positive patients produced high levels of HOCl and reciprocally low post-incubation VCR levels. HOCl and VCR concentrations in this group were significantly different than other groups studied. Both APAP and T inhibited VCR degradation in the sera of the chemotherapy group but not to the same degree. The effects seen here were consistent for both ALL and the lymphoma/solid tumor cases. Our results indicate that HOCl can increase VCR degradation in vitro in the serum and this effect is significantly more pronounced in pediatric patients undergoing chemotherapy.


Strengthening the enabling environment for women and girls: what is the evidence in social and structural approaches in the HIV response?
There is growing interest in expanding public health approaches that address social and structural drivers that affect the environment in which behaviour occurs. Half of those living with HIV infection are women. The sociocultural and political environment in which women live can enable or inhibit their ability to protect themselves from acquiring HIV. This paper examines the evidence related to six key social and structural drivers of HIV for women: transforming gender norms; addressing violence against women; transforming legal norms to empower women; promoting women's employment, income and livelihood opportunities; advancing education for girls and reducing stigma and discrimination. The paper reviews the evidence for successful and promising social and structural interventions related to each driver. This analysis contains peer-reviewed published research and study reports with clear and transparent data on the effectiveness of interventions. Structural interventions to address these key social and structural drivers have led to increasing HIV-protective behaviours, creating more gender-equitable relationships and decreasing violence, improving services for women, increasing widows' ability to cope with HIV and reducing behaviour that increases HIV risk, particularly among young people.


Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with direct-cut forage on feedlot performance, carcass characteristics, and diet digestibility of finishing steers.
Two experiments were conducted to evaluate the effects of feeding corn modified wet distillers grain plus solubles (MWDGS) co-ensiled with direct-cut forage (DC) to beef steers, on feedlot performance and total tract digestibility. In Exp. 1, sixty-four crossbred Angus steers (n = 64; 329 ± 43 kg) were blocked by BW and randomly assigned to 1 of 4 dietary treatments: 1) corn-silage and soybean meal (CON), 2) DC co-ensiled with MWDGS (CO-EN), 3) haylage mixed with MWDGS at feeding (H+WDG), and 4) haylage mixed with dry distillers grains plus solubles at feeding (H+DDG). Steers were harvested when they reached an endpoint of 1.1 cm of 12th-rib back fat. In Exp. 2, four ruminally cannulated beef steers (initial BW = 556 ± 31 kg) were used in a 4 × 4 Latin square to evaluate digestibility of diets used in Exp. 1. Experimental periods were 14 d in length with 10 d for diet adaptation and 4 d for sample collection. Three linear orthogonal contrasts were used to compare effects of 1) CON vs. diets containing distillers grains (DGD), 2) CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and 3) H+WDG vs. H+DDG. In Exp. 1, DMI was less (P < 0.001) for steers fed CON compared with those fed DGD and greatest (P < 0.001) for steers fed CO-EN compared with MIX. Corn-silage- and soybean-meal-fed steers had more days on feed than those fed DGD (P = 0.001). Body weight gain (P = 0.02) was greater for CO-EN compared with MIX. Fat thickness at the 12th and 13th ribs was greater (P = 0.03) for DGD steers compared with CON steers. Hot carcass weight was greater (P = 0.03) for steers fed CO-EN compared with those fed MIX. Steers fed CON resulted in greater marbling scores (P = 0.01) compared DGD-fed steers. Longissimus muscle area was greater (P = 0.01) for CON-fed steers compared with all other treatments. In Exp. 2, no differences (P > 0.10) in DM, OM, or N intakes were observed. Apparent total tract DM (P = 0.01) and N (P = 0.02) digestibility were greatest in steers fed CON compared with all others. Steers fed DGD had less (P = 0.02) rumen NH(3) concentrations compared with CON. The CON diet resulted in greater molar concentrations of VFA (P = 0.03) and decreased acetate to propionate ratio (P = 0.03) compared with all DGD. These data suggest that feeding MWDGS co-ensiled with direct-cut forage results in reduced diet digestibility but equal or greater feedlot performance and similar carcass and characteristics when compared with a corn diet supplemented with soybean meal and diets where MWDGS and DDGS were added at the mixer.


Gender difference in antidiuretic response to desmopressin.
Increased age and female gender are well-known risk factors for the development of desmopressin-induced hyponatremia. However, little focus has been on exploring gender differences in the antidiuretic response to desmopressin. Based on an exploratory analysis from three clinical trials, we report a significant gender difference in the effects of desmopressin on nocturnal urine volume that could not be explained by pharmacokinetic differences. Mean desmopressin concentration profiles were tested for covariates, and age and gender were not statistically significant and only weight was significant for log(C(max)) (P = 0.0183) and borderline significant for log(AUC) (P = 0.0571). The decrease in nocturnal urine volume in nocturia patients treated with desmopressin over 28 days was significantly larger for women at the lower desmopressin melt doses of 10 and 25 μg than for men. The ED(50) for men was modeled to be 43.2 μg and 16.1 μg for women, with the ED(50) men/women estimated to be 2.7 (1.3-8.1 95% CI), corresponding to significantly higher sensitivity to desmopressin in women. An increasing incidence of hyponatremia with increasing dose was found, and at the highest dose level of 100 μg decreases in serum sodium were approximately twofold greater in women over 50 yr of age than in men. A new dose recommendation stratified by gender is suggested in the treatment of nocturia: for men, 50- to 100-μg melt is an efficacious and safe dose, while for women a dose of 25 μg melt is recommended as efficacious with no observed incidences of hyponatremia. Areas for further research are proposed to uncover pathophysiological mechanism(s) behind these gender differences.


[The analysis of self-evaluation of stomatological health in patients with partial absence of teeth].
The aspects related to self-assessment of dental health in patients with partial absence of teeth were analyzed using questionnaire survey, clinical examination of patients and extracting data from health questionnaires from patient's medical records were studied. Patients with a partial absence of teeth most often admit to dental medical organization with complaints about impaired chewing function. At the same time, most of respondents with largest number of such complaints belong to older age groups: 45-54 and 55-62 years. The main problems with maxillofacial region of patients are of aesthetic character - the general aesthetics of the face and smile. As well as main factors of patients' anxiety, significant for dental health self-assessment are facial distortion and unattractive smile. The insufficient knowledge and literacy of studied group of patients regarding their need to restore partial absence of teeth, possible consequences of partial absence of teeth and the lack of information about modern methods of orthodontic care for patients with partial absence of teeth were established. The criterion of following the recommendations of attending physician and regularity of brushing teeth is defined and described. The application of study data makes it possible to optimize organization of orthodontic care for patients with partial absence of teeth.


Effects of oral caffeine pretreatment on response to intravenous nicotine and cocaine.
Previous research suggests that under conditions of chronic daily caffeine administration, caffeine increases the effects of nicotine. Little is known about the effects of caffeine pretreatment on response to nicotine under infrequent caffeine administration conditions. The present study examined whether infrequent (not on consecutive days) acute oral caffeine administration alters subject-rated, physiological, and monetary value effects of intravenous nicotine in regular users of caffeine, tobacco, and cocaine. To determine the specificity of effects of caffeine on response to nicotine, the effects of caffeine administration on response to intravenous cocaine (another short-acting stimulant) were also studied. Fourteen (1 woman) volunteers participated in this 3-4 week, double-blind, inpatient study. Volunteers participated in 10 experimental conditions in pseudo-randomized order, in which oral caffeine (250 mg/70 kg) or placebo was administered 1 hr before an intravenous injection, consisting of nicotine (1 or 2 mg/70 kg), cocaine (15 or 30 mg/70 kg), or saline. Infrequent acute caffeine pretreatment attenuated the increase resulting from 2 mg/70 kg nicotine administration on ratings of "rush," "good effects," "liking," "high," and "drowsy/sleepy." Caffeine had no significant effect on physiological response to nicotine. Caffeine had no significant effect on subject-rated and physiological response to cocaine, with the exception that caffeine significantly augmented blood pressure response to cocaine. In contrast to the previous research using chronic caffeine maintenance, these data suggest that infrequent acute caffeine administration may attenuate nicotine effects.


Targeted recovery of novel phylogenetic diversity from next-generation sequence data.
Next-generation sequencing technologies have led to recognition of a so-called 'rare biosphere'. These microbial operational taxonomic units (OTUs) are defined by low relative abundance and may be specifically adapted to maintaining low population sizes. We hypothesized that mining of low-abundance next-generation 16S ribosomal RNA (rRNA) gene data would lead to the discovery of novel phylogenetic diversity, reflecting microorganisms not yet discovered by previous sampling efforts. Here, we test this hypothesis by combining molecular and bioinformatic approaches for targeted retrieval of phylogenetic novelty within rare biosphere OTUs. We combined BLASTN network analysis, phylogenetics and targeted primer design to amplify 16S rRNA gene sequences from unique potential bacterial lineages, comprising part of the rare biosphere from a multi-million sequence data set from an Arctic tundra soil sample. Demonstrating the feasibility of the protocol developed here, three of seven recovered phylogenetic lineages represented extremely divergent taxonomic entities. These divergent target sequences correspond to (a) a previously unknown lineage within the BRC1 candidate phylum, (b) a sister group to the early diverging and currently recognized monospecific Cyanobacteria Gloeobacter, a genus containing multiple plesiomorphic traits and (c) a highly divergent lineage phylogenetically resolved within mitochondria. A comparison to twelve next-generation data sets from additional soils suggested persistent low-abundance distributions of these novel 16S rRNA genes. The results demonstrate this sequence analysis and retrieval pipeline as applicable for exploring underrepresented phylogenetic novelty and recovering taxa that may represent significant steps in bacterial evolution.


242 breakpoints in the 200-kb deletion-prone P20 region of the DMD gene are widely spread.
Using whole cosmids as probes, we have mapped 242 DMD/BMD deletion breakpoints located in the major deletion hot spot of the DMD gene. Of these, 113 breakpoints were mapped more precisely to individual restriction enzyme fragments in the distal 80 kb of the 170-kb intron 44. An additional 12 breakpoints are distributed over the entire region, with no significant local variation in frequency. Furthermore, deletion sizes vary and are not influenced by the positions of the breakpoints. This argues against a predominant role of one or a few specific sequences in causing frequent rearrangements. It suggests that structural characteristics or a more widespread recombinogenic sequence makes this region so susceptible to deletion. Our study revealed several RFLPs, one of which is a 300-bp insertion/deletion polymorphism. Abnormally migrating junction fragments are found in 81% of the precisely mapped deletions and are highly valuable in the diagnosis of carrier females.


An overview of FDA regulatory requirements for new medical devices.
US national healthcare expenditure reached over 2 trillion dollars in 2007. medical device expenditure has remained nearly a constant 6% of the total healthcare expenditure. medical technology may be one of the driving factors increasing healthcare costs. the number of medical device (which includes diagnostic tests) and laboratory equipment manufacturers, and investment in research for medical devices continue to rise. medical device manufacturers can receive a higher than average return on investment if they successfully navigate the food and drug administration (FDA) approval process. this paper focuses on the series of steps a manufacturer can pursue to facilitate the introduction of a new device to the us market. a review of the FDA regulations and current literature was conducted. exemption from a full review by the FDA owing to substantial equivalence is one of the pathways a manufacturer can pursue for quicker and easier approval of the new device. three classes of devices are reviewed, as are some of the key regulations governing them. the regulations for advertising and promotion are still unclear because of the gray area that exists between the federal trade commission and the FDA. this paper concludes by summarizing the advertising and promotion regulations set forth by the FDA during the post-approval phase.


Three-view bedside ultrasound for the differentiation of acute respiratory distress syndrome from cardiogenic pulmonary edema.
Bedside ultrasound is being increasingly used by emergency physicians (EPs) for the differentiation of acute dyspnea in critically ill patients. Lung ultrasound is emerging as a highly sensitive tool in diagnosing alveolar interstitial edema with the presence of diffuse "B-lines" arising from the pleural line. However, when used independently, lung ultrasound is unable to differentiate between cardiogenic and noncardiogenic causes of pulmonary edema. This case report describes a rapid 3-view or "triple scan" sonographic examination to differentiate acute respiratory distress syndrome (ARDS) from cardiogenic pulmonary edema.


Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review of Literature.
Colorectal cancer is the third most common cancer worldwide with a high mortality rate at the advanced stages. However, colorectal cancer is not a single type of tumor; its pathogenesis depends on the anatomical location of the tumor and differs between right side and left side of the colon. Tumors in the proximal colon (right side) and distal colon (left side) exhibit different molecular characteristics and histology. In the right-sided tumors, mutations in the DNA mismatch repair pathway are commonly observed; and these tumors generally have a flat histology. In the left-sided tumors, chromosomal instability pathway-related mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors demonstrate polypoid-like morphology. Therapy responses are totally different between these tumor entities. Left-sided colorectal cancer (LCRC) patients benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based regimes, and targeted therapies such as anti- epidermal growth factor receptor (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC) patients do not respond well to conventional chemotherapies, but demonstrate more promising results with immunotherapies because these tumors have high antigenic load. For the development of effective therapy regimes and better treatment options, it is essential to evaluate right-sided and left-sided tumors as separate entities, and design the therapy regime considering the differences between these tumors.


Evaluation of Patient-Reported Outcome Measures of Positive Psychosocial Constructs in Children and Adolescent/Young Adults with Cancer: A Systematic Review of Measurement Properties.
Introduction: Children, adolescents, and young adults with cancer are a vulnerable population in whom improvements in psycho-oncology care would be valuable. We previously published a scoping review exploring what is known about positive psychological constructs in this population. A key finding was that evidence-based patient-reported outcome measures (PROMs) were needed to standardize psycho-oncology research. Methods: We undertook a systematic review of measurement properties focused on PROMs in the pediatric and adolescent/young adults (AYAs) with cancer populations. We searched for PROMs that measured at least 1 of 15 previously identified, key positive constructs. This systematic review followed COSMIN guidelines, considered the gold standard manual for systematic reviews of measurement properties. Results: We identified 20 (22 if proxy reports are counted separately) unique PROMs that met inclusion criteria. Of those, only five were recommended for use given the current evidence. The remainder may be used if no alternative exists. Only eight PROMs had any evidence of content validity, considered the most important psychometric property by COSMIN. Many studies were at risk of bias owing to incomplete or suboptimal methods. Discussion: Five PROMs are considered reliable for the pediatric and AYA with cancer populations. A number of PROMs require additional research to ensure their items and instructions are comprehensive, relevant, and comprehensible to children and AYAs. Given the overall lack of research, this review may be considered a starting point for the future refinement of a core set of PROMs to measure positive psychological constructs.


Evening-types show highest increase of sleep and mental health problems during the COVID-19 pandemic-multinational study on 19 267 adults.
Individual circadian type is a ubiquitous trait defining sleep, with eveningness often associated with poorer sleep and mental health than morningness. However, it is unknown whether COVID-19 pandemic has differentially affected sleep and mental health depending on the circadian type. Here, the differences in sleep and mental health between circadian types are examined globally before and during the COVID-19 pandemic. The sample collected between May and August 2020 across 12 countries/regions consisted of 19 267 adults with information on their circadian type. Statistical analyses were performed by using Complex Sample procedures, stratified by country and weighted by the number of inhabitants in the country/area of interest and by the relative number of responders in that country/area. Evening-types had poorer mental health, well-being, and quality of life or health than other circadian types during the pandemic. Sleep-wake schedules were delayed especially on working days, and evening-types reported an increase in sleep duration. Sleep problems increased in all circadian types, but especially among evening-types, moderated by financial suffering and confinement. Intermediate-types were less vulnerable to sleep changes, although morningness protected from most sleep problems. These findings were confirmed after adjusting for age, sex, duration of the confinement, or socio-economic status during the pandemic. These findings indicate an alarming increase in sleep and mental health problems, especially among evening-types as compared to other circadian types during the pandemic.


Rheological Properties and Melt Spinning Application of Controlled-Rheology Polypropylenes via Pilot-Scale Reactive Extrusion.
Based on pilot-scale twin-screw reactive extrusion, the structural and rheological properties of controlled-rheology polypropylenes (CR-PPs) are investigated, where the effects of peroxide content and extrusion conditions such as screw configuration, extrusion temperature, and screw speed are prioritized. The active chain cleavage reaction by a small peroxide content of less than 600 ppm inside the extruder gradually increases the melt index and narrows the molecular weight distribution of CR-PPs, thereby affording favorable properties that are applicable to the fiber spinning process. The mechanical properties of CR-PPs are slightly degraded owing to the generation of unsaturated chain ends during the reactive extrusion, which suppresses crystal growth. Under all extrusion conditions, the chain scission and thermal degradation of polypropylene samples occur actively in the harsh twin-screw extruder compared with those in the mild twin-screw extruder. Finally, it is confirmed that CR-PPs can be suitably applied to the melt-spinning process for staple fiber production, thereby guaranteeing a more stable spinning process window against draw resonance instability.