Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages.
The beneficial effects of moderate red wine consumption have been attributed, in part, to the presence of antioxidant components. Oxidant stress is an activating stimulus for the NF (nuclear factor)-KB/Rel family of transcription factors, which have binding sites in the promoter regions of many genes involved in inflammatory and immune responses. The effect of lipopolysaccharide (LPS)-stimulated activation of NF-KB and the subsequent production of tumor necrosis factor alpha (TNF-alpha) and NO was determined in the macrophage cell line RAW 264.7. Unexpectedly, the wine polyphenolics quercetin and resveratrol and the antioxidant N-acetylcysteine (NAC) did not inhibit LPS-induced activation of the NF-KB complex p50/65, as determined by mobility shift. Quercetin inhibited LPS-induced p50/50. Northern blot analysis indicated that quercetin (0.1 and 0.2 mM) inhibited LPS-dependent production of inducible nitric oxide synthase (iNOS) mRNA and decreased NO release, as measured by the Griess reaction. This flavonoid had no effect on LPS-induced TNF-alpha mRNA, but decreased LPS-stimulated TNF-alpha release, as measured by ELISA. Resveratrol (0.05 and 0.1 mM) posttranscriptionally decreased LPS-induced nitrite release. It increased basal levels of TNF-alpha mRNA and protein and enhanced LPS-induced TNF-alpha mRNA and cytokine release. Our results do not support the view that wine antioxidants inhibit LPS-induced NF-KB activation but instead that they have a more selective action on genes activated by LPS.


Post-traumatic upper extremity reflex sympathetic dystrophy. Clinical course, staging, and classification of clinical forms.
RSD is a symptom complex, representing an exaggerated response to injury or tissue damage. The amplification of the normal responses probably occurs both in the periphery and in the central nervous system. Diagnostic criteria are still under discussion, and treatment modalities are still directed toward the symptoms because the pathophysiology is not known. The pain of the condition may be sympathetically maintained of sympathetically independent (or both), and sympathetic blockade is useful in the former category. Treatment modalities must be directed toward optimizing both comfort and function of the affected extremity. Such treatment programs might occur in a multidisciplinary setting.


Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929.
Harpagophytum procumbens (Pedaliaceae) has been used for the treatment of pain and arthritis. The effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, reverse transcription-polymerase chain reaction, prostaglandin E(2) (PGE(2)) immunoassay, and nitric oxide detection on mouse fibroblast cell line L929. The aqueous extract of Harpagophytum procumbens was shown to suppress PGE(2) synthesis and nitric oxide production by inhibiting lipopolysaccharide-stimulated enhancement of the cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) mRNAs expressions in L929 cells. These results suggest that Harpagophytum procumbens exerts anti-inflammatory and analgesic effects probably by suppressing cyclooxygenase-2 and iNOS expressions.


Online Graduation of Doctors During the COVID-19 Pandemic.
This article was migrated. The article was marked as recommended. In March 2020, the United Kingdom declared a nationwide lockdown, a public health intervention in response to the COVID-19 pandemic. In addition, the increasing pressures on the country's publicly funded healthcare system, the National Health Service, required the early graduation of final year medical students so that they could join the workforce. Bristol Medical School responded to this health crisis by graduating 226 final year students. Since social distancing policies resulted in the prohibition of social gatherings, university graduation ceremonies were cancelled. The medical school felt it important to mark the students' qualification as these young doctors were to begin their careers amidst an unprecedented global health emergency. An online graduation ceremony was held on the video conferencing platform Zoom. This was attended by university staff and students from their homes across the UK and elsewhere in the world. Students commemorated their qualification by submitting photographs of themselves celebrating in homemade graduation robes and mortar boards which were included in the online event. The ceremony was a memorable occasion and created a sense of community in a time of social isolation. This novel situation gave rise to a unique celebration attracting media coverage and was reported on national TV and radio news bulletins along with newspapers. The structure for the online graduation ceremony outlined in this paper may be replicated for other graduation ceremonies or celebrations affected by the COVID-19 lockdown.


Predictors of late pulmonary vein reconnection in patients with arrhythmia recurrence after cryoballoon ablation-per vein analysis including cardiac computed tomography-based anatomic factors.
To identify predictors of individual late pulmonary vein (PV) reconnection after second-generation cryoballoon (CB2) ablation. Anatomic indicators of late pulmonary vein reconnection (LPVR) post-CB2 ablation have not yet been studied on an individual PV level, nor weighed against clinical and procedural factors. Clinical, procedural, and PV anatomic data from 125 patients with a repeat procedure for arrhythmia recurrence after index CB2 ablation were analyzed. Preprocedural computed tomography (CT) evaluated 486 PVs for measurement of size; shape (ovality index); carina width; and orientation angle in frontal (superior/inferior) and transversal (anterior/posterior) plane (with horizontal line 0° as reference and upper/lower half circle as positive/negative value, respectively). Durable isolation in all PVs was demonstrated in 50/125 (40%) patients. Late reconnection rates at the different PVs were as follows: 16% left superior (LS), 12% left inferior (LI), 17% right superior (RS), and 31% right inferior (RI) PV. Multivariable analysis performed per vein showed following independent determinants predicting LPVR: ovality index [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.07-2.41, P = 0.022] and carina width (OR 0.75, CI 0.59-0.96, P = 0.024) for LSPV; carina width (OR 0.71, CI 0.53-0.95, P = 0.020) for LIPV; frontal angle (OR 0.91, CI 0.87-0.95, P < 0.001) for RIPV; and transversal angle (OR 1.15, CI 1.03-1.31, P = 0.032) for RSPV. Cardiac CT-based evaluation of anatomic PV characteristics presented higher predictive value compared to clinical and procedural variables for individual LPVR after CB2 ablation. Pre-procedural identification of unfavourable PV anatomy might be important to tailor the ablation approach.


Influences of spatial scale and soil permeability on relationships between land cover and baseflow stream nutrient concentrations.
The Little Miami River (LMR) basin, dominated by agriculture, contains two geologically-distinct regions; a glaciated northern till plain with soils three times more permeable than a southern, pre-Wisconsinan drift plain. The influences of two landscape measures, percent row crop cover (%RCC, computed at three spatial scales), and soil permeability (PERM), on baseflow nutrient concentrations were modeled using linear regressions. Quarterly water samples collected for four years were analyzed for nitrate-N (NN), Kjeldahl-N (KN), total-N (TN), and total-P (TP). In till plain streams (n = 17), NN concentrations were 8.5-times greater than drift plain streams (n = 18), but KN and TP were 20-40% lower at comparable %RCC. These differences resulted in TN/TP molar ratios >80 in till plain streams, but <6 in drift plain streams. For till plain steams regression models based on %RCC accounted for 79% of the variance in NN concentrations but only 27% in drift plain streams. However, regressions on %RCC accounted for 68-75% of the KN and TP concentration variance in the drift plain streams but essentially none in the till plain. Catchment PERM influenced the regional NN/KN ratios which were 10-fold higher in the drift plain streams. For both till and drift streams the catchment scale %RCC gave the best predictions of NN, a water soluble anion, but the smaller spatial scales produced better models for insoluble nutrient species (e.g., KN and TP). Published literature on Ohio streams indicates that these inter-regional differences in nutrient ratios have potential implications for aquatic biota in the receiving streams.


Decreased ventilatory function in hard metal workers.
To study individual effects on pulmonary function of exposure to hard metal including cobalt. All of the workers in a hard metal company (583 men and 120 women) were examined for smoking, respiratory symptoms, ventilatory function, occupational history of exposure to hard metal, and present exposure to airborne cobalt. The ventilatory function indices (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory volume in one second per cent (FEV1%), peak expiratory flow (PEF), mid-maximal flow (MMF), forced expiratory flow at 50% vital capacity (V50), forced expiratory flow at 25% vital capacity (V25)) were standardised for height and age and expressed as a percentage of predicted values. Two way analysis of variance of indices of ventilatory function showed that an interaction of hard metal exposure and smoking decreased %V50 for both men and women. Among the currently exposed men, those with asthmatic symptoms (defined as reversible dispnoea with wheeze) had significantly lower %FVC, %FEV1%, %PEF, %MMF, %V50, and %V25 than did workers without asthma. The ventilatory disfunction did not differ between exposed and non-exposed workers with asthmatic symptoms. Even among the men without asthmatic symptoms, %V50 was significantly lowered by the interaction of hard metal exposure and smoking. The multilinear regression analysis of indices of ventilatory function for all of the subjects on sex, smoking (Brinkman index), exposure to hard metal, and asthmatic symptoms showed that asthmatic symptoms and smoking had significant effects on all variables and that the decrease in %V25 was associated with hard metal exposure. In the currently exposed and non-exposed workers, multilinear regression analysis applying indices for cobalt exposure (mean cobalt concentration, duration of exposure, and cumulative dose) showed that not only asthmatic symptoms or smoking but also duration of exposure had significant decreasing effects on %FVC, %MMF, and %V25. Occupational exposure to hard metal probably causes impairment of ventilatory function in a dose dependent manner.


[Pathology also subject to RCTs].
Pathology is a diagnostic field and pathologists do not treat patients. It would at first seem that randomised controlled trials (RCTs) are not an option in this field. However, pathology is often the gold standard for diagnostics in RCTs and guidelines. With the arrival of new techniques in pathology diagnostics, particularly molecular techniques, it seems that more objective data can be collected. An RCT recently studied the effect of an electronic reminder for further diagnostics of Lynch syndrome, a hereditary disorder that the pathologist can detect by testing microsatellite instability. Studies to make pathology reporting more evidence-based are also very likely. Even the role of pathology in the diagnosis and treatment of patients needs to be made more verifiable.


The association between student socioeconomic status and student-teacher relationships on math achievement.
The importance of math achievement in the early grades has been well documented. Two variables that have independently been found to be strong predictors of math achievement are student-teacher relationships (STR) and socioeconomic status (SES). The present study investigates the interaction between STR and SES on student math achievement using the Early Childhood Longitudinal Study, a nationally representative data set. The participants included approximately 8,380 first-grade students, 2,930 teachers, and 860 schools, representing a weighted sample of approximately 3.15 million students or 90% of the population. Multilevel modeling, controlling for student-, teacher-, and school-level factors, found that both STR and SES had a strong relationship with student math achievement. There was also a statistically significant moderation effect between close STR and SES on math achievement, suggesting that close STR are beneficial for all students, but are especially beneficial for students from low SES backgrounds. Further, educational implications for research, policy, and practice are provided. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The scientific contributions of Brenda Bigland-Ritchie.
Brenda Bigland-Ritchie has made seminal contributions to our understanding of skeletal muscle physiology--the energy cost of muscle when it shortens or is forcibly stretched, the relationship between EMG and force, the behavior of single motor units, and above all, the processes underlying neuromuscular fatigue. More than this, she has stimulated inquiry into the search for reflex mechanisms which may serve to balance the activity of the spinal cord with that of the fatiguing muscles. Her use of human volunteers for much of this work is extraordinary, and represents a major strength. Equally important are her well known and widely cited manuscripts. Not only are her findings clearly described and depicted, but every attempt is made to relate her results to the fatigue processes measured in animal or isolated tissue preparations.


[Possibilities of the automatic data processing in differential diagnosis of arteriosclerotic cardiosclerosis and rheumatic heart disease complicated by auricular fibrillation].
The possibility of applying some mathematical methods for automating the process of differential diagnosis between atherosclerotic cardiosclerosis and rheumatic heart diseases complicated by auricular fibrillation, based on employing computing technique in processing the cardiointervalographic findings, is discussed. The processing of cardiointervalograms taken in 2 groups of patients with diseases in question (totaling 49 persons) aged over 45 evidenced that in the differential diagnosis mathematical expectation and dispersion of the R-R intervals duration are most informative signs. It is shown that for the purpose of automatic diagnosis of atherosclerotic cardiosclerosis and rheumatic heart diseases complicated by auricular fibrillation with the method under discussion the sufficient length of cardiointervalograms equals 130--150 R--R-intervals.


Mapping Fusarium wilt race 1 resistance genes in cotton by inheritance, QTL and sequencing composition.
Knowledge of the inheritance of disease resistance and genomic regions housing resistance (R) genes is essential to prevent expanding pathogen threats such as Fusarium wilt [Fusarium oxysporum f.sp. vasinfectum (FOV) Atk. Sny & Hans] in cotton (Gossypium spp.). We conducted a comprehensive study combining conventional inheritance, genetic and quantitative trait loci (QTL) mapping, QTL marker-sequence composition, and genome sequencing to examine the distribution, structure and organization of disease R genes to race 1 of FOV in the cotton genome. Molecular markers were applied to F(2) and recombinant inbred line (RIL) interspecific mapping populations from the crosses Pima-S7 (G. barbadense L.) × 'Acala NemX' (G. hirsutum L.) and Upland TM-1 (G. hirsutum) × Pima 3-79 (G. barbadense), respectively. Three greenhouse tests and one field test were used to obtain sequential estimates of severity index (DSI) of leaves, and vascular stem and root staining (VRS). A single resistance gene model was observed for the F(2) population based on inheritance of phenotypes. However, additional inheritance analyses and QTL mapping indicated gene interactions and inheritance from nine cotton chromosomes, with major QTLs detected on five chromosomes [Fov1-C06, Fov1-C08, (Fov1-C11 ( 1 ) and Fov1-C11 ( 2)) , Fov1-C16 and Fov1-C19 loci], explaining 8-31% of the DSI or VRS variation. The Fov1-C16 QTL locus identified in the F(2) and in the RIL populations had a significant role in conferring FOV race 1 resistance in different cotton backgrounds. Identified molecular markers may have important potential for breeding effective FOV race 1 resistance into elite cultivars by marker-assisted selection. Reconciliation between genetic and physical mapping of gene annotations from marker-DNA and new DNA sequences of BAC clones tagged with the resistance-associated QTLs revealed defenses genes induced upon pathogen infection and gene regions rich in disease-response elements, respectively. These offer candidate gene targets for Fusarium wilt resistance response in cotton and other host plants.


Lead aerosol baseline: concentration at White Mountain and Laguna Mountain, California.
The lead aerosol concentration at White Mountain, California, may be regarded as the present baseline concentration for atmospheric lead for the continental United States. The seasonal trend of lead aerosols at White Mountain and Laguna Mountain shows a summer maximum and a winter minimum. This is because both mountain sampling sites are well above the thermal (radiation) inversion, which normally occurs in the winter, trapping pollutants below the inversion boundary.


Family-based pediatric weight management interventions in US primary care settings targeting children ages 6-12 years old: A systematic review guided by the RE-AIM framework.
Obesity is a pandemic that disproportionately affects children from vulnerable populations in the USA. Current treatment approaches in primary care settings in the USA have been reported to be insufficient at managing pediatric obesity, primarily due to implementation challenges for healthcare systems and barriers for families. While the literature has examined the efficacy of pediatric obesity interventions focused on internal validity, it lacks sufficient reporting and analysis of external validity necessary for successful translation to primary care settings. We conducted a systematic review of the primary-care-setting literature from January 2007 to March 2020 on family-based pediatric weight management interventions in both English and/or Spanish for children ages 6-12 years in the USA using the Reach, Efficacy/Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. A literature search, using PRISMA guidelines, was conducted in January 2022 using the following electronic databases: Medline Ovid, Embase, and Cochrane Library. 22 270 records were screened, and 376 articles were reviewed in full. 184 studies were included. The most commonly reported dimensions of the RE-AIM framework were Reach (65%), Efficacy/Effectiveness (64%), and Adoption (64%), while Implementation (47%) and Maintenance (42%) were less often reported. The prevalence of reporting RE-AIM construct indicators ranged greatly, from 1% to 100%. This systematic review underscores the need for more focus on external validity to guide the development, implementation, and dissemination of future pediatric obesity interventions based in primary care settings. It also suggests conducting additional research on sustainable financing for pediatric obesity interventions.


Cardiotoxicity of Immune Checkpoint Inhibitors.
Immunotherapies, particularly immune checkpoint inhibitors (ICI), are revolutionary cancer therapies being increasingly applied to a broader range of cancers. Our understanding of the mechanism, epidemiology, diagnosis, and treatment of cardiotoxicity related to immunotherapies remains limited. We aim to synthesize the limited current literature on cardiotoxicity of ICIs and to share our opinions on the diagnosis and treatment of this condition. The incidence of ICI-associated myocarditis ranges from 0.1 to 1%. Patients with ICI-associated myocarditis often have a fulminant course with a case fatality rate of 25-50%. The diagnosis of this condition poses many challenges because independently a normal electrocardiogram, biomarkers, or a preserved left ventricular function do not rule out ICI-associated myocarditis. Endomyocardial biopsy should be pursued when clinical suspicion remains despite normal non-invasive tests. Data on optimal screening and surveillance tools are lacking. Cessation of ICIs, combined with high dose corticosteroids and other immunosuppressant approaches are the cornerstones of the treatment of ICI-associated myocarditis. This condition may recur when patients are re-challenged with these agents and the decision to resume ICIs should be made through a multidisciplinary discussion. Immunotherapies have changed the landscape of cancer treatment. Recognizing and managing cardiotoxicity related to ICIs is of critical importance. Our understanding of ICI-cardiotoxicity has improved, but large information gaps remain for further research. Due to the high case fatality rate, any type of cardiac symptoms or signs in a patient who has recently started an ICI should prompt consideration of ICI-cardiotoxicity.


Prevalence and correlates of unhealthy weight control behaviors: findings from the national longitudinal study of adolescent health.
A recent study examined the prevalence, clinical correlates, age trends, and stability of unhealthy weight control behaviors (UWCB; purging and diet pill use) in a nationally representative sample of Norwegian boys and girls. The purpose of this study was to provide similar, comparative analyses for a nationally representative sample of American youth. Data were extracted from the restricted use data files of survey Waves I, II, and III of the National Longitudinal Study of Adolescent Health (Add Health), selecting all participants who at Wave I had provided information on age, sex, and UWCB. Using UWCB information, three groups were created (purging, diet pill use, and no recent UWCB "controls") and compared on indicators of adverse health or mental health. Girls consistently were more likely than boys to report UWCB. UWCB were significantly associated with higher body mass index, self-perception of being overweight, low self-esteem, depression, and delinquency. Prevalence estimates for purging remained relatively constant across the three survey waves; in contrast, diet pill use was especially common at Wave III. Age trends, gender differences, and clinical correlates of change in the likelihood of UWCB between Waves I-III were all identified in analyses comparing purging and diet pill use in American adolescents. Females and older adolescents were specifically more likely to engage in pill use than purging, and individuals with increased weight dissatisfaction, a history of delinquent behaviors, more depression symptoms, or lower self-esteem were more likely to engage in an unhealthy weight control behavior over time. While the Norwegian study found that prevalence of purging was lower among young adult participants, our results suggested that there were no significant differences in prevalence between age groups.


Yield of Surveillance Colonoscopy in Older Adults with a History of Polyps: A Systematic Review and Meta-Analysis.
The benefit of surveillance colonoscopy in older adults is not well described. To quantify the detection of colorectal cancer (CRC) and advanced polyps during surveillance colonoscopy in older adults with a history of colon polyps. We conducted a systematic review (MEDLINE, Cochrane Library, Web of Science, and Embase) for all published studies through May 2020 in adults age > 70 undergoing surveillance colonoscopy. The main outcome was CRC and advanced polyps detection. We performed meta-analysis to pool results by age (>70 vs. 50-70). The search identified 6239 studies, of which 569 underwent full-text review and 64 data abstraction, of which 19 were included. The risk of detecting CRC (N = 11) was higher in those >70 compared to 50-70 (risk ratio 1.5 (95% CI 1.1-2.2); risk difference 0.8% (95% CI -0.2%-1.8%)). Similarly, the risk of detecting advanced polyps (N = 8) was higher in those >70 compared to 50-70 (risk ratio 1.3 (95% CI 1.2-1.3), risk difference 2.7% (95% CI 1.3%-4.0%)). Most studies did not stratify results by baseline polyp risk. The detection of CRC and advanced polyps during surveillance colonoscopy in older individuals was higher than in younger controls; however, the absolute risk increase for both was small. These differences must be weighed against competing medical problems and limited life expectancy in older adults when making decisions about surveillance colonoscopy. More primary data on the risks of CRC and advanced polyps accounting for number of past colonoscopies, prior polyp risk, and duration of time since last polyp are needed.


Loganin alleviates testicular damage and germ cell apoptosis induced by AGEs upon diabetes mellitus by suppressing the RAGE/p38MAPK/NF-κB pathway.
Diabetes mellitus (DM) damages male reproduction at multiple levels, such as endocrine secretion, spermatogenesis and penile erection. We herein investigated the protective effects and mechanism of loganin targeting the advanced glycation end products (AGEs)/receptor for AGEs (RAGE)/p38 mitogen-activated protein kinase (p38MAPK)/NF-κB signalling pathway. Loganin relieved the general DM symptoms and decreased the blood glucose level of KK-Ay DM mice. Haematoxylin-eosin staining demonstrated that loganin ameliorated testicular histology and function and enhanced the activities of testis-specific markers lactate dehydrogenase (LDH), acid phosphatase (ACP) and gamma-glutamyl transferase (γ-GT). Loganin also showed evident anti-oxidative stress, anti-apoptotic and anti-inflammatory effects on DM-induced reproductive damage by restoring glutathione (GSH) level and superoxide dismutase (SOD) activity, as well as reducing reactive oxygen species (ROS) level and Bax/Bcl-2 ratio in vivo and in vitro. Western blotting exhibited that loganin significantly inhibited the AGEs/RAGE/p38MAPK/NF-κB signalling pathway. Acridine orange and ethidium bromide staining (AOEB) and Western blotting showed that loganin in combination with inhibitors of RAGE, p38MAPK and NF-κB exerted stronger anti-apoptotic effects on AGE-induced GC-2 cell damage compared with loganin alone. In conclusion, loganin can protect against DM-induced reproductive damage, probably by suppressing the AGEs/RAGE/p38MAPK/NF-κB pathway.


Downregulation of Aurora-A overrides estrogen-mediated growth and chemoresistance in breast cancer cells.
Estrogen is known to play a causative role in the development of sporadic breast cancers and chemoresistance. However, studies on the mechanism and proteins involved in mediating the oncogenic effects of estrogen are very limited. Recently, Aurora-A, a centrosomal protein kinase, which induces centrosome amplification and genomic instability, has been shown to be upregulated during long-term treatment of rats with estrogen and was implicated in estrogen-induced oncogenesis. Herein, we present results of the studies carried out in short-term in vitro cultures to understand the regulation of Aurora-A by estrogen and the effect of downregulation of Aurora-A on estrogen-induced breast tumorigenesis and chemoresistance. Treatment of breast cancer cells with 10 nM 17beta-estradiol (E(2)) resulted in the upregulation of Aurora-A levels in an estrogen receptor-dependent manner. However, the upregulation by E(2) was not restricted to Aurora-A alone. Following release from the tamoxifen-induced arrest, the appearance of Aurora-A in the presence of estradiol in MCF7 cells coincided with the appearance of other mitotic markers suggesting that the spike in Aurora-A levels is an indirect consequence of estrogen-mediated cell proliferation. Thus, at least in short-term in vitro studies, Aurora-A is not a specific direct target of estrogen. However, downregulation of Aurora-A by RNA interference led to a significant decrease in estrogen-induced, anchorage-dependent, and independent growth of MCF7 cells. Moreover, knockdown of Aurora-A could overcome estrogen-induced decrease in docetaxel sensitivity of MCF7 cells. Cumulatively, we propose that the upregulation of Aurora-A by estrogen in short-term in vitro cultures is an indirect consequence of estrogen-induced cell proliferation. Nevertheless, Aurora-A inhibitors could be exploited to override the effects of estrogen on breast tumorigenesis and chemoresistance.


Antibiotic prescribing patterns in the pediatric emergency department at Georgetown Public Hospital Corporation: a retrospective chart review.
The increase in antimicrobial-resistant infections has led to significant morbidity, mortality, and healthcare costs. The impact of antimicrobial resistance is greatest on low-income countries, which face the double burden of fewer antibiotic choices and higher rates of infectious diseases. Currently, Guyana has no national policy on rational prescribing. This study aims to characterize antibiotic prescribing patterns in children discharged from the emergency department at Georgetown Public Hospital Corporation (GPHC), as per the World Health Organization (WHO) prescribing indicators. A retrospective chart review of pediatric patients (aged 1 month-13 years) seen in the GPHC emergency department between January and December 2012 was conducted. Outpatient prescriptions for eligible patients were reviewed. Patient demographics, diagnosis, and drugs prescribed were recorded. The following WHO Prescribing Indicators were calculated: i) average number of drugs prescribed per patient encounter, ii) percentage of encounters with an antibiotic prescribed, iii) percentage of antibiotics prescribed by generic name, and iv) percentage of antibiotics prescribed from essential drugs list or formulary. Eight hundred eleven patient encounters were included in the study. The mean patient age was 5.55 years (s = 3.98 years). 59.6 % (n = 483) patients were male. An average of 2.5 drugs were prescribed per encounter (WHO standard is 2.0). One or more antibiotic was prescribed during 36.9 % (n = 299) of all encounters (WHO standard is 30 %). 90.83 % of antibiotics were prescribed from the essential drugs formulary list and 30 % of the prescriptions included the drug's generic name. The average duration of antibiotic therapy was 5.73 days (s = 3.53 days). Of the 360 antibiotics prescribed, 74.7 % (n = 269) were broad-spectrum. B-lactam penicillins were prescribed most frequently (51.4 %), with amoxicillin being the most popular choice (33.9 %). The most common diagnoses were injuries (25.8 %), asthma (20 %), respiratory infections (19.5 %), and gastrointestinal infections (12.1 %). Per WHO prescribing indicators, the pediatric emergency department at GPHC has higher than standard rates of antibiotic use and polypharmacy. The department excels in adhering to the essential drug formulary. Our findings provide support for investigating drug utilization in other Guyanese settings, and to work towards developing a national rational prescribing strategy.


[Psoriasis in 2016 : Co-morbidities and therapeutic update].
Recognition of psoriasis as a chronic systemic inflammatory condition rather than just a skin disease is now widely accepted in the medical community. Association with joint involvement and depressive symptoms has been established for many years and several studies demonstrated an increased risk for comorbidities. These include the metabolic syndrome, obesity, hypertension, diabetes, dyslipidemia, non-alcoholic fatty liver disease, inflammatory bowel disease, and an increased incidence of cardiovascular events among those patients.


Ultrasound diagnosis of an obstructive cardiac rhabdomyoma with severe hydrops and hypoplastic lungs. A case report.
Cardiac rhabdomyomas of the fetus and neonate are benign cardiac muscle hamartomas with an incidence of 0.027% in pediatric autopsies. This is the third reported case of prenatally diagnosed cardiac rhabdomyoma, the second with severe hydrops and the only one associated with aortic valve hypoplasia and hypoplastic lungs.


The effect of adapting Hospital at Home to facilitate implementation and sustainment on program drift or voltage drop.
Translating evidence-based interventions from study conditions to actual practice necessarily requires adaptation. We implemented an evidence-based Hospital at Home (HaH) intervention and evaluated whether adaptations could avoid diminished benefit from "voltage drop" (decreased benefit when interventions are applied under more heterogeneous conditions than existing in studies) or "program drift." (decreased benefit arising from deviations from study protocols). Patients were enrolled in HaH over a 6-month pilot period followed by nine quarters of implementation activity. The program retained core components of the original evidence-based HaH model, but adaptations were made at inception and throughout the implementation. These adaptations were coded as to who made them, what was modified, for whom the adaptations were made, and the nature of the adaptations. We collected information on length of stay (LOS), 30-day readmissions and emergency department (ED) visits, escalations to the hospital, and patient ratings of care. Outcomes were assessed by quarter of admission. Selected outcomes were tracked and fed back to the program leadership. We used logistic or linear regression with an independent variable included for the numerical quarter of enrollment after the initial 6-month pilot phase. Models controlled for season and for patient characteristics. Adaptations were made throughout the implementation period. The nature of adaptations was most commonly to add or to substitute new program elements. HaH services substituting for a hospital stay were received by 295 patients (a mean of 33, range 11-44, per quarter). A small effect of quarter from program inception was seen for escalations (OR 1.09, 95% CI 1.01 to 1.18, p = 0.03), but no effect was observed for LOS (- 0.007 days/quarter; SE 0.02, p = 0.75), 30 day ED visit (OR 0.93, 95% CI 0.86 to 1.01, p = 0.09), 30-day readmission (OR 1.00, 95% CI 0.93 to 1.08, p = 0.99), or patient rating of overall hospital care (OR for highest overall rating 0.99, 95% CI 0.93 to 1.05, p = 0.66). We made adaptations to HaH at inception and over the course of implementation. Our findings indicate that adaptations to evidence-based programs may avoid diminished benefits due to potential 'program drift' or 'voltage drop.' Not applicable. This study is not a clinical trial by the International Committee of Medical Journal Editors (ICMJE) definition because it is an observational study "in which the assignment of the medical intervention is not at the discretion of the investigator."


Glesatinib Exhibits Antitumor Activity in Lung Cancer Models and Patients Harboring MET Exon 14 Mutations and Overcomes Mutation-mediated Resistance to Type I MET Inhibitors in Nonclinical Models.
Purpose:MET exon 14 deletion (METex14 del) mutations represent a novel class of non-small cell lung cancer (NSCLC) driver mutations. We evaluated glesatinib, a spectrum-selective MET inhibitor exhibiting a type II binding mode, in METex14 del-positive nonclinical models and NSCLC patients and assessed its ability to overcome resistance to type I MET inhibitors.Experimental Design: As most MET inhibitors in clinical development bind the active site with a type I binding mode, we investigated mechanisms of acquired resistance to each MET inhibitor class utilizing in vitro and in vivo models and in glesatinib clinical trials.Results: Glesatinib inhibited MET signaling, demonstrated marked regression of METex14 del-driven patient-derived xenografts, and demonstrated a durable RECIST partial response in a METex14 del mutation-positive patient enrolled on a glesatinib clinical trial. Prolonged treatment of nonclinical models with selected MET inhibitors resulted in differences in resistance kinetics and mutations within the MET activation loop (i.e., D1228N, Y1230C/H) that conferred resistance to type I MET inhibitors, but remained sensitive to glesatinib. In vivo models exhibiting METex14 del/A-loop double mutations and resistance to type I inhibitors exhibited a marked response to glesatinib. Finally, a METex14 del mutation-positive NSCLC patient who responded to crizotinib but later relapsed, demonstrated a mixed response to glesatinib including reduction in size of a MET Y1230H mutation-positive liver metastasis and concurrent loss of detection of this mutation in plasma DNA.Conclusions: Together, these data demonstrate that glesatinib exhibits a distinct mechanism of target inhibition and can overcome resistance to type I MET inhibitors. Clin Cancer Res; 23(21); 6661-72. ©2017 AACR.


Activation of transient receptor potential vanilloid-3 inhibits human hair growth.
In the current study, we aimed at identifying the functional role of transient receptor potential vanilloid-3 (TRPV3) ion channel in the regulation of human hair growth. Using human organ-cultured hair follicles (HFs) and cultures of human outer root sheath (ORS) keratinocytes, we provide the first evidence that activation of TRPV3 inhibits human hair growth. TRPV3 immunoreactivity was confined to epithelial compartments of the human HF, mainly to the ORS. In organ culture, TRPV3 activation by plant-derived (e.g., eugenol, 10-1,000 μM) or synthetic (e.g., 2-aminoethoxydiphenyl borate, 1-300 μM) agonists resulted in a dose-dependent inhibition of hair shaft elongation, suppression of proliferation, and induction of apoptosis and premature HF regression (catagen). Human ORS keratinocytes also expressed functional TRPV3, whose stimulation induced membrane currents, elevated intracellular calcium concentration, inhibited proliferation, and induced apoptosis. Of great importance, these effects on ORS keratinocytes were all mediated by TRPV3, as small interfering RNA-mediated silencing of TRPV3 effectively abrogated the cellular actions of the above agonists. These findings collectively support the concept that TRPV3 signaling is a significant player in human hair growth control. Therefore, TRPV3 and the related intracellular signaling mechanism might function as a promising target for pharmacological manipulations of clinically relevant hair growth disorders.


Association of SEEK1 and psoriatic arthritis in two distinct Canadian populations.
To examine the relationship between SNP +39604 in SEEK1 and psoriatic arthritis (PsA) in two distinct Canadian populations. 103 patients with PsA and 105 ethnically matched controls from Newfoundland and 202 patients with PsA and 100 controls from Ontario were studied. Patients and controls were genotyped for SNP +39604 of SEEK1 by time of flight mass spectrometry, using the Sequenom platform. Genomic DNA was amplified by the Dynal RELI SSO HLA-Cw* typing kit for HLA-C typing. The frequency of the minor SEEK1(T) allele in subjects with PsA and controls was 48.5% and 32.4%, respectively (odds ratio (OR) = 2.0; p = 0.017), in the Newfoundland population and 46.5% and 38.0%, respectively (OR = 1.4; p = 0.16), in the Ontario population. Although SEEK1 is associated with PsA, particularly in the Newfoundland population, multivariate analysis showed that SEEK1 does not seem to be a further susceptibility factor if the HLA-Cw*0602 status is already known. No association was noted between SEEK1(T) allele and onset of psoriasis, PsA, or arthritis pattern. SEEK1 is associated with PsA in the Newfoundland founder population. This association is probably due to linkage disequilibrium between SEEK1 and HLA-Cw*0602 in this population.


Author Diversity on Clinical Practice Guideline Committees.
Reports have demonstrated that women overall and women physicians, in particular, are underrepresented as authors of clinical practice guidelines. This analysis used publicly available information to explore the diversity of rehabilitation-related clinical practice guideline authors by gender, race, and ethnicity. Primary analysis identified authors' gender, race, ethnicity, and visible minority status. Two sets were analyzed: (1) clinical practice guidelines by Department of Veterans Affairs (VA) categorized as "Rehabilitation" or "Pain" (n = 7; VA clinical practice guidelines) and (2) a set (n = 10) published in the United States (US) from 2019 to 2021 that were selected because of low numbers of inclusion at less than 20% women authors. Key findings include that among physician authors, both the VA and US clinical practice guidelines underrepresented women (15 [24.2%] and 27 [16.7%], respectively) and those coded as a racial or ethnic minority were particularly underrepresented. Notably, women authors overall were equally represented (92 [50.0%]) in the VA clinical practice guidelines. The US clinical practice guidelines had women authors who were underrepresented (36 [19.0%]). Secondary analysis of the entire set of VA clinical practice guidelines (n = 21) found gaps in diversity-related content. Clinical practice guidelines have far-reaching health and economic impacts, and addressing disparities in the diversity of author teams and/or gaps in diversity-related content is of paramount importance.


Prenatal diagnosis and 47,XXY.
In this contribution, we consider detection of 47,XXY by a variety of available methods. These include traditional invasive procedures, screening with maternal serum analytes and fetal ultrasound, and most recently cell-free fetal DNA. Since its introduction in the late 1960s, prenatal genetic diagnosis has evolved greatly. Serendipitious detection of 47,XXY was not infrequent when prenatal genetic diagnosis routinely involved testing by the invasive procedures CVS and amniocentesis. In 2013 this is much less common and relatively few pregnancies in the U.S. and Europe are tested without prior screening protocols, traditionally maternal serum analyte and fetal ultrasound (NT). These protocols are not designed to identify 47,XXY or other X-chromosome aneuploides and with screening by analysis of cell-free DNA in maternal blood, this situation may or may not be altered. Increased numbers of cases could be detected if intake increases and vendors offer information on 47,XXY. A further consideration is that ability of array CGH to detect microdeletions or microduplications below resolution of a karyotype could make return to direct testing using an invasive procedure attractive.


Stress-induced hyperalgesia instead of analgesia in patients with chronic musculoskeletal pain.
Many individuals with chronic musculoskeletal pain (CMP) show impairments in their pain-modulatory capacity. Although stress plays an important role in chronic pain, it is not known if stress-induced analgesia (SIA) is affected in patients with CMP. We investigated SIA in 22 patients with CMP and 18 pain-free participants. Pain thresholds, pain tolerance and suprathreshold pain ratings were examined before and after a cognitive stressor that typically induces pain reduction (SIA). Whereas the controls displayed a significant increase in pain threshold in response to the stressor, the patients with CMP showed no analgesia. In addition, increased pain intensity ratings after the stressor indicated hyperalgesia (SIH) in the patients with CMP compared to controls. An exploratory analysis showed no significant association of SIA or SIH with spatial pain extent. We did not observe significant changes in pain tolerance or pain unpleasantness ratings after the stressor in patients with CMP or controls. Our data suggest that altered stress-induced pain modulation is an important mechanism involved in CMP. Future studies need to clarify the psychobiological mechanisms of these stress-induced alterations in pain processing and determine the role of contributing factors such as early childhood trauma, catastrophizing, comorbidity with mental disorders and genetic predisposition.


NEW MODE OF GENETIC TRANSFER IN STREPTOCOCCUS FAECALIS VAR. LIQUEFACIENS.
Raycroft, Ruth E. (The Pennsylvania State University, University Park), and L. N. Zimmerman. New mode of genetic transfer in Streptococcus faecalis var. liquefaciens. J. Bacteriol. 87:799-801. 1964.-When chloramphenicol-resistant mutants are grown in mixed culture with the sensitive wild type of Streptococcus faecalis var. liquefaciens 31, a transfer of chloramphenicol resistance occurs. (The marker is stable through at least five transfers.) The transfer mechanism is not inhibited by deoxyribonuclease, nor is it phage-mediated; genetic transfer is apparently dependent upon cell contact. Although kinetic studies have yet to be completed, preliminary data indicate a high efficiency (2.2 per donor cell in some experiments) of transmission. Two levels of drug resistance, 7 and 50 mug, were transferred; in each case, recipient cells expressed the donor's degree of resistance.


Mistaken clinical and pathologic diagnoses of Hodgkin's disease: a Southwest oncology group study.
Expert hematopathology review of initial diagnostic material was required for patients registered in a Southwest Oncology Group trial of advanced Hodgkin's disease (HD). Of 287 cases reviewed, 36 (13%) had been misdiagnosed as HD. The clinical and histologic features of the first 180 patients reviewed by the expert panel, including 21 (12%) patients for whom errors in diagnosis were discovered, were retrospectively analyzed to ascertain why mistakes in diagnosis had occurred. The most common error in pathologic interpretation was to confuse other malignant lymphomas with HD (14/21 patients), particularly large cell lymphomas with pleomorphic features and Reed-Sternberg-like cells. Rare conditions (Lennert's lymphoma or angioimmunoblastic lymphadenopathy) were also confused with HD. Mixed-cellularity and lymphocyte-depleted HD were the most frequently mistaken cell types (14/21 patients) and nodular-sclerosing HD was the least mistaken (two of 21). The clinical features of these 21 patients showed a high incidence of unusual extranodal sites of disease involvement including thyroid (one patient), ovary (one), skin (two), bone (three), and lung (seven). We next analyzed the clinical features of the remaining 107 cases in order to prospectively identify, based on atypical clinical preparations, patients who might not have HD. Subsequent histologic review revealed mistaken diagnosis in 15 patients (14%). Eight of the 15 patients (53%) were correctly identified as having disease other than HD on the basis of clinical presentation alone. Atypical clinical presentations, particularly unusual extranodal sites of disease along with a presumptive diagnosis of mixed cellularity or lymphocyte-depleted HD, should forewarn the clinical and the pathologist of a possible error in diagnosis.


Acetabular Coverage Decreases at the End of Skeletal Growth: A 3DCT Study of Healthy Hips.
Abnormalities in size and position of the acetabulum have been linked to both developmental dysplasia of the hip and femoroacetabular impingement. Owing to its 3-dimensional (3D) complexity, plain radiography and cross-sectional studies [computed tomography (CT) and magnetic resonance imaging] have limitations in their ability to capture the complexity of the acetabular 3D anatomy. The goal of the study was to use 3D computed tomography reconstructions to identify the acetabular lunate cartilage and measure its size at varying ages of development and between sexes. Patients aged 10 to 18 years with asymptomatic hips and a CT pelvis for appendicitis were reviewed. Patients were stratified by sex and age: preadolescent (10 to 12), young adolescent (13 to 15), and old adolescent (16 to 18) in equal proportions. Materialise 3-matic was used to generate a 3D pelvic model, and the acetabular lunate cartilage surface area was calculated. The lunate cartilage was divided into anatomic segments: superior (11:00 to 1:00), anterior (1:00 to 4:00), and posterior (8:00 to 11:00). The femoral head surface area was calculated to control for patient size. Mixed effects models were generated predicting segment size where side was treated as a repeated measure. Absolute and relative (lunate cartilage to femoral head) models were generated. Sixty-two patients (124 hips) were included. Females showed a significant decrease in femoral head coverage as age increased overall and in the 3 subsegments. The majority of changes occurred between the preadolescent and young adolescent groups. Males did not show an overall change, but the superior and anterior anatomic subgroups showed a significant decrease in coverage between the young and old adolescent groups. Male lunate cartilages were absolutely, but not relatively, larger than females. No clinically significant side-to-side differences were noted. The relative femoral head coverage by the acetabular lunate cartilage reduced with increasing age, suggesting the growth of the femoral head outpaces the acetabular lunate cartilage's growth. This was more prominent in females. This study has important implications for expected acetabular coverage changes in the latter aspects of pediatric and adolescent development. Level III-diagnostic study.


Sticholysin, Sphingomyelin, and Cholesterol: A Closer Look at a Tripartite Interaction.
Actinoporins are a group of soluble toxic proteins that bind to membranes containing sphingomyelin (SM) and oligomerize to form pores. Sticholysin II (StnII) is a member of the actinoporin family produced by Stichodactyla helianthus. Cholesterol (Chol) is known to enhance the activity of StnII. However, the molecular mechanisms behind this activation have remained obscure, although the activation is not Chol specific but rather sterol specific. To further explore how bilayer lipids affect or are affected by StnII, we have used a multiprobe approach (fluorescent analogs of both Chol and SM) in combination with a series of StnII tryptophan (Trp) mutants to study StnII/bilayer interactions. First, we compared StnII bilayer permeabilization in the presence of Chol or oleoyl-ceramide (OCer). The comparison was done because both Chol and OCer have a 1-hydroxyl, which helps to orient the molecule in the bilayer (although OCer has additional polar functional groups). Both Chol and OCer also have increased affinity for SM, which StnII may recognize. However, our results show that only Chol was able to activate StnII-induced bilayer permeabilization; OCer failed to activate it. To further examine possible Chol/StnII interactions, we measured Förster resonance energy transfer between Trp in StnII and cholestatrienol, a fluorescent analog of Chol. We could show higher Förster resonance energy transfer efficiency between cholestatrienol and Trps in position 100 and 114 of StnII when compared to three other Trp positions further away from the bilayer binding region of StnII. Taken together, our results suggest that StnII was able to attract Chol to its vicinity, maybe by showing affinity for Chol. SM interactions are known to be important for StnII binding to bilayers, and Chol is known to facilitate subsequent permeabilization of the bilayers by StnII. Our results help to better understand the role of these important membrane lipids for the bilayer properties of StnII.


Integrative analysis of tissue-specific methylation and alternative splicing identifies conserved transcription factor binding motifs.
The exact role of intragenic DNA methylation in regulating tissue-specific gene regulation is unclear. Recently, the DNA-binding protein CTCF has been shown to participate in the regulation of alternative splicing in a DNA methylation-dependent manner. To globally evaluate the relationship between DNA methylation and tissue-specific alternative splicing, we performed genome-wide DNA methylation profiling of mouse retina and brain. In protein-coding genes, tissue-specific differentially methylated regions (T-DMRs) were preferentially located in exons and introns. Gene ontology and evolutionary conservation analysis suggest that these T-DMRs are likely to be biologically relevant. More than 14% of alternatively spliced genes were associated with a T-DMR. T-DMR-associated genes were enriched for developmental genes, suggesting that a specific set of alternatively spliced genes may be regulated through DNA methylation. Novel DNA sequences motifs overrepresented in T-DMRs were identified as being associated with positive and/or negative regulation of alternative splicing in a position-dependent context. The majority of these evolutionarily conserved motifs contain a CpG dinucleotide. Some transcription factors, which recognize these motifs, are known to be involved in splicing. Our results suggest that DNA methylation-dependent alternative splicing is widespread and lay the foundation for further mechanistic studies of the role of DNA methylation in tissue-specific splicing regulation.


Global Systematic Review of Common Mental Health Disorders in Adults Living with HIV.
By reviewing the most recent common mental health disorders (CMHD) studies in people living with HIV (PLWH) (2018-2020), this review discusses the prevalence of CMHD, factors associated with CMHD in PLWH, mental health in PLWH from vulnerable groups, the impact of CMHD on HIV disease progression and adherence to antiretroviral therapy and the efficacy of different treatment approaches. After screening for eligibility 142 studies were included in the final systematic review. Only 27% of studies were conducted in Sub-Saharan Africa, which carries the highest burn of HIV disease globally. Despite the well-established increased risk of CMHD in PLWH, the current prevalence remains high, with studies reporting 28%-62% of PLWH having mental health symptoms. Despite the significant challenges that CMHDs present to successful HIV treatment, there are many mental health treatments and interventions which can improve outcomes in PLWH and opportunities to task-shift and integrate mental health care with HIV care.


Mucinous adenocarcinoma associated with a chronic perianal fistula - a review of cases from a single institution.
The purpose of this study was to evaluate the clinicopathological features of mucinous adenocarcinoma associated with perianal fistulas (MAF), to assess the importance of preoperative MRI analysis, and to determine the optimal surgery. We performed a retrospective analysis of the data from seven patients with MAF treated at our hospital between 2000 and 2013, and herein discuss the importance of preoperative magnetic resonance imaging (MRI) and of radical surgery. The male to female ratio was 5:2, and the mean age of the patients was 63 years old (28-70). The median duration of chronic fistulation was 16 years (5-40). The tumor extension was classified as II+III+IV in five patients and as II+III in 2 patients according to the Sumikoshi classification, as determned by pelvic MRI. The performed surgeries were 3 abdominoperineal resections with sacral resection and 4 pelvic exenterations with sacral resection. Two local recurrences developed in patients with R1 resection, and 1 distant metastasis occurred in 1 patient with R0 resection. For patients with MAF, a curative surgical resection is the only definitive treatment that can be expected to provide a good prognosis. The application of the Sumikoshi classification using MRI may provide a precise assessment of the extension of MAF, which can allow the appropriate surgery to be selected for the patients with MAF.


Genome-wide identification and expression profiling of auxin response factor (ARF) gene family in maize.
Auxin signaling is vital for plant growth and development, and plays important role in apical dominance, tropic response, lateral root formation, vascular differentiation, embryo patterning and shoot elongation. Auxin Response Factors (ARFs) are the transcription factors that regulate the expression of auxin responsive genes. The ARF genes are represented by a large multigene family in plants. The first draft of full maize genome assembly has recently been released, however, to our knowledge, the ARF gene family from maize (ZmARF genes) has not been characterized in detail. In this study, 31 maize (Zea mays L.) genes that encode ARF proteins were identified in maize genome. It was shown that maize ARF genes fall into related sister pairs and chromosomal mapping revealed that duplication of ZmARFs was associated with the chromosomal block duplications. As expected, duplication of some ZmARFs showed a conserved intron/exon structure, whereas some others were more divergent, suggesting the possibility of functional diversification for these genes. Out of these 31 ZmARF genes, 14 possess auxin-responsive element in their promoter region, among which 7 appear to show small or negligible response to exogenous auxin. The 18 ZmARF genes were predicted to be the potential targets of small RNAs. Transgenic analysis revealed that increased miR167 level could cause degradation of transcripts of six potential targets (ZmARF3, 9, 16, 18, 22 and 30). The expressions of maize ARF genes are responsive to exogenous auxin treatment. Dynamic expression patterns of ZmARF genes were observed in different stages of embryo development. Maize ARF gene family is expanded (31 genes) as compared to Arabidopsis (23 genes) and rice (25 genes). The expression of these genes in maize is regulated by auxin and small RNAs. Dynamic expression patterns of ZmARF genes in embryo at different stages were detected which suggest that maize ARF genes may be involved in seed development and germination.


Education in airway management.
In airway management, poor judgment, education and training are leading causes of patient morbidity and mortality. The traditional model of medical education, which relies on experiential learning in the clinical environment, is inconsistent and often inadequate. Curriculum change is underway in many medical organisations in an effort to correct these problems, and airway management is likely to be explicitly addressed as a clinical fundamental within any new anaesthetic curriculum. Competency-based medical education with regular assessment of clinical ability is likely to be introduced for all anaesthetists engaged in airway management. Essential clinical competencies need to be defined and improvements in training techniques can be expected based on medical education research. Practitioners need to understand their equipment and diversify their airway skills to cope with a variety of clinical presentations. Expertise stems from deliberate practice and a desire constantly to improve performance with a career-long commitment to education.


Central versus ambulatory blood pressure for predicting mortality and cardiovascular events in hemodialysis patients: a multicenter cohort study.
Studies in the general population suggest that central blood pressure (BP) may be superior to peripheral BP in risk assessment. Although ambulatory brachial BP is recognized as the most reliable BP measurement in the dialysis population, there is no comparison of office central BP with ambulatory BP regarding risk stratification in these patients. In a multicenter prospective study of dialysis patients, central BP was measured noninvasively on a midweek nondialysis day, with interdialytic ambulatory BP and predialysis BP also collected. The primary outcomes were a composite of major adverse cardiovascular events (MACE) and all-cause mortality. Agreement between central and ambulatory BP was assessed using Cohen's Kappa index and Bland--Altman plot. Linear and nonlinear Cox regression models were used to determine the association of BP parameters with outcomes. A total of 368 patients were recruited and 366 underwent central BP measurement. Central BP had a moderate agreement with ambulatory BP in defining hypertension (κ = 0.42) with wide limits of agreement in Bland--Altman analysis. After a median follow-up of 51.5 months, central pulse pressure, ambulatory SBP and ambulatory pulse pressure were associated with all-cause mortality, whereas all BP parameters, except for predialysis DBP, were significant predictors of MACE. However, whenever evaluated in a stepwise variable selection Cox model, only ambulatory pulse pressure, but not any central BP, was determined as the best candidate for prediction of both all-cause mortality and MACE. Nonlinear Cox models revealed no significant nonlinear trend of the association between central BP and outcomes. Central BP is predictive of all-cause mortality and cardiovascular events in dialysis patients but its prognostic value does not outperform ambulatory peripheral BP. Our data support the superiority of ambulatory BP in the dialysis population.


[Myelofibrosis with myeloid metaplasia. A study of 24 consecutive patients].
A series of 24 consecutive patients affected by myelofibrosis with myeloid metaplasia was reviewed. The clinical-pathological features at onset were similar to those reported in literature; in particular in all the patients we observed splenomegaly and the typical leuko-erythroblastic picture in peripheral blood. The median survival of our series was of 57 months; the deaths were caused by severe anaemia and/or infection and/or haemorrhage; the blastic terminal transformations were rare. According to other authors, unfavourable prognostic factors in our patients were: male sex, advanced age, hepatomegaly, the presence of systemic signs, anaemia, leukocytosis, leukopenia, high number of circulating erythroblasts, thrombocytopenia, osteomyelosclerosis. We have confirmed the clinical value of three staging prognostic systems: the system proposed by Njoku based on haemoglobin level and reticulocytes number, the system proposed by Visani based on haemoglobin and circulating myeloid precursors number, the system proposed by Dupriez based on haemoglobin and white blood cells number.


Is the worldwide epidemic of obesity a communicable feature of globalization?
Globalization has a major impact on both economic and social determinants in public health. The current worldwide epidemic in obesity needs to be considered in the context of globalization as a communicable rather than non-communicable process. There is increasing evidence that global trends in lifestyle, eating behavior and cultural adaptation contribute to the rapid increase in obesity around the world. Thus, obesity may be defined as a "socially-contagious" feature of globalization. Furthermore, infectious agents are being identified that may cause obesity by central mechanisms or by modulating adipocyte function or at least by contributing to the chronic inflammatory milieu of the metabolic syndrome. Therefore, globalization may indeed form a critical platform for these pathogens to fuel the obesity epidemic. Understanding obesity in the light of globalization as a communicable disorder will allow outlining better avenues of prevention and treatment.


Polyethylene bio-degradation by caterpillars of the wax moth Galleria mellonella.
Plastics are synthetic polymers derived from fossil oil and largely resistant to biodegradation. Polyethylene (PE) and polypropylene (PP) represent ∼92% of total plastic production. PE is largely utilized in packaging, representing ∼40% of total demand for plastic products (www.plasticseurope.org) with over a trillion plastic bags used every year [1]. Plastic production has increased exponentially in the past 50 years (Figure S1A in Supplemental Information, published with this article online). In the 27 EU countries plus Norway and Switzerland up to 38% of plastic is discarded in landfills, with the rest utilized for recycling (26%) and energy recovery (36%) via combustion (www.plasticseurope.org), carrying a heavy environmental impact. Therefore, new solutions for plastic degradation are urgently needed. We report the fast bio-degradation of PE by larvae of the wax moth Galleria mellonella, producing ethylene glycol.


Smear layer removal by EGTA.
The purpose of this study was to compare the effects of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N', N'-tetraacetic acid (EGTA) and EDTA on removal of the smear layer by using scanning electron microscopy. Fifteen single-rooted teeth were instrumented to size 60. Three teeth served as the control group, and the remaining teeth were assigned into two groups. After instrumentation, root canals of the first group were irrigated with 10 ml of 17% EDTA, and the second group was irrigated with 10 ml of 17% EGTA for 2 min. Both were then irrigated with 10 ml of 5% NaOCl. The teeth in the control group were irrigated with only 10 ml of 5% NaOCl. Then the specimens were sectioned longitudinally and processed for scanning electron microscopy. The results showed that the smear layer was completely removed by EDTA, but it caused erosion of the tubuli. EGTA was somewhat effective in removing the smear layer without inducing erosion. Our results suggest that EGTA is an alternative chelator for removing the smear layer.


Vibrio sinaloensis sp. nov., isolated from the spotted rose snapper, Lutjanus guttatus Steindachner, 1869.
Nine bacterial strains were studied by means of rep-PCR, 16S rRNA gene sequence analysis, DNA-DNA hybridization and physiological characterization. Typing analysis by means of rep-PCR showed that all nine strains were highly homogeneous, with similarities above 94 %. The strains were isolated from the same geographical area (Mazatlán, Sinaloa state, Mexico) and the same type of host (cultured rose snapper, Lutjanus guttatus), although from different individuals and organs. Comparison of the almost-complete 16S rRNA gene sequences of five strains showed that they belonged to the genus Vibrio and are closely related to the type strains of Vibrio brasiliensis and Vibrio hepatarius, with similarity values ranging from 97.9 to 98.1 % and from 97.4 to 97.8 %, respectively. The DNA-DNA hybridization value of strain CAIM 797(T) with the type strain of V. brasiliensis (CAIM 495(T)) was 47.5 %, with a reciprocal value of 44.7 %. The main phenotypic features of the strains were in agreement with the phylogenetic and genomic data. The results presented here support the description of a novel species, for which the name Vibrio sinaloensis sp. nov. is proposed, with strain CAIM 797(T) (=CECT 7298(T)) as the type strain.


The molecular identification of the midget chromosome from the rye genome.
The diminutive "midget" chromosome is found in plants containing a wheat nuclear genome with a substituted rye cytoplasm. This cytoplasmic substituted line arose during successive backcrossing of a wheat/rye amphiploid to wheat as the recurrent male parent. Southern and in situ hybridization with a dispersed repeat sequence specific for rye, R173, indicates that the midget chromosome originates from within the rye genome. Various DNA markers previously mapped to group 1 chromosomes of wheat and barley were used to trace the origin of the midget chromosome from within the rye genome. Ten short arm and 36 long arm probes were used and one marker was identified, which hybridizes to the midget chromosome and maps to the proximal region of the long arm of chromosome 1R. An additional marker was generated from a genomic library of the line containing the midget chromosome. This also maps to the long arm of 1R. The results indicate that the midget chromosome contains a small segment of the long arm of chromosome 1R.


Female chromosomes in cockerel ejaculates.
We describe a polymerase chain reaction which amplifies part of the Eco RI repeat unit of the fowl W chromosome. The resulting 447 bp fragment enables DNA from female birds to be identified. The composition of this DNA is confirmed by a nested polymerase chain reaction which specifically amplifies a known internal 263 bp region in this fragment. Using this technique it is possible to follow the fate of female cells in male germline chimaeras. The polymerase chain reaction fragment can be traced in cells of the embryonic and hatchling gonad and in adult sperm implying that cells containing the W chromosome are capable of being processed through the avian testis.


Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery.
The primary aim was to compare long-term health-related quality of life (HRQoL) in patients undergoing sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND), with or without axillary metastases. Secondary aims were to a) investigate agreement between objectively measured and self-reported lymphoedema and b) compare, with respect to HRQoL, women with objective arm lymphoedema without subjective ratings and those with no objective but subjective ratings of arm lymphoedema. The three study groups were defined by axillary surgery: 1) SLNB alone (N = 140), 2) ALND in patients without axillary metastases (N = 125) and 3) ALND in patients with axillary metastases (N = 155). Preoperatively, one and three years postoperatively arm volume was measured and questionnaires regarding self-perceived symptoms of arm lymphoedema and HRQoL were completed (The Swedish Short Form-36 Health Survey, SF-36). Out of the original 516 who had axillary surgery, 420 (81%) completed the study. There were no statistically significant differences in HRQoL between the three study groups. No statistically significant agreement was found between self-perceived and objectively measured arm lymphoedema. Women without self-perceived arm lymphoedema, regardless of objective arm lymphoedema or not, scored higher on all eight SF-36 domains than those who reported self-perceived arm lymphoedema. Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, have a decreased long-term health-related quality of life. This indicates that more attention should be given to the subjective reports of symptom in order to better help these women.


Agonist-sensitive and -insensitive intracellular Ca2+ pools. Separate Ca(2+)-releasing mechanisms revealed by manoalide and benzohydroquinone.
The mechanism of action of a novel compound, 2,5-di-(t-butyl)-1,4-benzohydroquinone (BHQ), used to modulate cell free cytosolic Ca2+ concentration ([Ca2+]i) was studied in AR42J cells and pancreatic acini by using single-cell fluorescence techniques applied to Fura-2-loaded cells. In the presence of extracellular Ca2+ (Ca(2+)out), BHQ induced a biphasic [Ca2+]i increase, an initial and rapid transient followed by a sustained increase. The initial increase was due to Ca2+ release from intracellular stores, being independent of Ca(2+)out. The sustained response was due to Ca2+ entry, being dependent on Ca(2+)out, blocked by La3+ and correlated with an increased rate of Mn2+ entry, all indicative of increased plasma-membrane permeability to Ca2+. Treatment of AR42J cells with BHQ for about 5 min reversibly blocked agonist-dependent Ca2+ release and oscillations, whereas agonist pretreatment decreased, but did not prevent, the effects of BHQ on [Ca2+]i. Accordingly, depletion of the Ins(1,4,5)P3-mobilizable pool in permeabilized AR42J cells by BHQ required 5 min of incubation, although inhibition of the internal Ca2+ pump by BHQ was rapid. These observations suggest that BHQ mobilized an additional intracellular Ca2+ pool that did not respond to changes in Ins(1,4,5)P3. Manoalide, an inhibitor of Ca2+ channels, inhibited agonist-evoked [Ca2+]i oscillation and [Ca2+]i increase in a dose- and time-dependent manner without significant effect on internal Ca2+ pumps and Ca2+ content of the internal stores. Manoalide also inhibited the BHQ-evoked [Ca2+]i increase in the absence and presence of Ca(2+)out. Neither BHQ nor manoalide affected Ins(1,4,5)P3 levels in resting or stimulated cells. Therefore, the effect of BHQ appears to involve unmasking of passive Ca(2+)-permeation pathways in the plasma and intracellular membranes that do not respond to cholecystokinin octapeptide, following its described inhibition of the internal-store Ca2+ pumps responsible for accumulating Ca2+ in these pools.


Study on propionyl-L-carnitine in chronic heart failure.
In patients with chronic heart failure, fatigue is independent of haemodynamic and neuroendocrine changes and possibly may be due to impaired muscle metabolism. Propionyl-L-carnitine, a carnitine derivative, was shown in previous studies to improve muscle metabolism. The objective of this study was to evaluate the effect of propionyl-L-carnitine on exercise capacity in mild moderate chronic heart failure patients, treated with ACE inhibitors and diuretics. This was a phase III, double-blind, randomized, parallel, multicentre study. The primary objective was the evaluation of the effect of propionyl-L-carnitine vs placebo on maximum exercise duration using a bicycle exercise test. The primary analysis performed in the intention-to-treat population (271 and 266 patients in propionyl-L-carnitine and placebo), showed no statistically significant difference between treatments. A difference of 15 s in favour of propionyl-L-carnitine was observed in the completer/complier population (P=0.092). An a priori specified subgroup analysis on patients stratified by baseline maximum exercise duration showed a trend of improvement in propionyl-L-carnitine patients with shorter maximum exercise duration. A non a priori specified analysis in patients stratified by ejection fraction (< or = 30% vs 30-40%), showed a statistically significant difference in maximum exercise duration in favour of propionyl-L-carnitine in those patients with a higher ejection fraction (40 s, P<0.01). There were no safety issues. The study fails to meet the primary objective, but confirms the good safety profile of propionyl-L-carnitine. An exploratory non-prespecified analysis suggests that propionyl-L-carnitine improves exercise capacity in patients with preserved cardiac function. This hypothesis needs to be confirmed by a specific tailored study.


Prophylactic antibiotic therapy in surgery.
Prophylactic (preventive) antibiotic therapy initiated preoperatively, with antibiotics administered in moderately high dosage for short periods, is recommended on the basis of experimental and prospective, randomized clinical trials for patients who require surgery that is likely to expose tissue planes to contamination. The value of prophylactic antibiotics in clean operations is not presently supported but must be considered in patients with decreased resistance and in those in whom infection of a prosthesis would have catastrophic results. In these patients topical antibiotics might prove useful and less dangerous. It is clear that surgical technique remains an important but as yet unmeasured factor in wound infection.


Building telehealth teams of the future through Interprofessional curriculum development: a five-year mixed methodology study.
Building the next generation of telehealth enabled professionals requires a mixture of team-based, interprofessional practice with novel technologies that connect providers and patients. Effective telehealth education is critical for the development of multidisciplinary training curricula to ensure workforce preparedness. In this study, we evaluated the impact of a formal telehealth education curriculum for interprofessional students through an online elective. Over 12 semesters, 170 students self-selected to enroll in the 3-credit hour interprofessional elective and took part in structured didactic, experiential and interprofessional learning opportunities. Mixed-method assessments show significant knowledge and confidence gains with students reflecting on their roles as future healthcare providers. The results from five years' worth of course data shows not only an opportunity to advance the individual knowledge of trainees, but a larger movement to facilitate changes in practice toward population health goals. Recent global health events have further highlighted the need for a rapid response to public health emergencies by highly trained provider teams who are able to utilize technology as the cornerstone for the continuity of care.


Molecular radiotheranostics for neuroendocrine tumours.
This article discusses the important role of nuclear medicine imaging and therapy in the management of neuroendocrine tumours (NETs). Somatostatin receptor scintigraphy has a high impact on patient management versus conventional imaging. Molecular radiotherapy is an important part of the management of patients with NETs. Selection of patients for molecular radiotherapy in NETs is based on uptake on their radionuclide imaging study. The imaging agent has the same mechanism of uptake as the therapeutic agent. Thus, the imaging study preselects patients that are likely to concentrate radiation within their tumours.


Oral health in pre-school children with asthma--followed from 3 to 6 years.
The aim of this study was to investigate caries and its determinants in preschool children with and without asthma, followed from 3 to 6 years. Caries, plaque, and gingivitis were examined at 3 and 6 years of age in 64 asthmatic children and 50 matched, healthy control children. Furthermore, at 6 years radiographic examination and saliva sampling were conducted. The parents were interviewed about various oral health-related factors. Initial caries increment between 3 and 6 years of age was statistically significant higher for children with asthma compared with children without asthma (P < 0.05). Asthmatic children had more bleeding gingivitis and a higher consumption of sugary drinks than healthy children at 3 years of age (P < 0.05). At both 3 and 6 years of age, the asthmatic children were more frequently mouth breathers than healthy children, only statistically significant for 6-year olds (P < 0.05). Preschool children with asthma at 3 years of age run a higher risk of developing caries lesions until 6 years of age compared with children without asthma. Children with asthma have a higher prevalence of bleeding gingivitis, a higher intake of sugary drinks and are more frequently mouth breathers than preschool children without asthma.


[Effect of cultivation temperature on nucleic acid level in bacteria Listeria monocytogenes and Yersinia pseudotuberculosis].
The relationship between the multiplication of bacteria, the content of nucleic acid and the specific rate of their growth during their batch cultivation in nutrient broth and mineral medium at temperatures of 37 degrees C and 4-6 degrees C was studied in the causative agents of saprozoonotic infections with L. monocytogenes and Y. pseudotuberculosis used as typical representatives of such bacteria. The content of DNA was shown to remain practically unchanged after the alteration of cultivation temperature and the conditions of nutrition. The linear relationship between the content of RNA and specific growth rate was registered both at 37 degrees C and 4-6 degrees C. However a higher content of RNA at low temperatures was found to correspond to one and the same specific growth rate, which was linked with the additional synthesis of this nucleic acid.


Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo.
Slow wave activity (SWA) is a characteristic brain oscillation in sleep and quiet wakefulness. Although the cell types contributing to SWA genesis are not yet identified, the principal role of neurons in the emergence of this essential cognitive mechanism has not been questioned. To address the possibility of astrocytic involvement in SWA, we used a transgenic rat line expressing a calcium sensitive fluorescent protein in both astrocytes and interneurons and simultaneously imaged astrocytic and neuronal activity in vivo. Here we demonstrate, for the first time, that the astrocyte network display synchronized recurrent activity in vivo coupled to UP states measured by field recording and neuronal calcium imaging. Furthermore, we present evidence that extensive synchronization of the astrocytic network precedes the spatial build-up of neuronal synchronization. The earlier extensive recruitment of astrocytes in the synchronized activity is reinforced by the observation that neurons surrounded by active astrocytes are more likely to join SWA, suggesting causality. Further supporting this notion, we demonstrate that blockade of astrocytic gap junctional communication or inhibition of astrocytic Ca2+ transients reduces the ratio of both astrocytes and neurons involved in SWA. These in vivo findings conclusively suggest a causal role of the astrocytic syncytium in SWA generation.


Picante: R tools for integrating phylogenies and ecology.
Picante is a software package that provides a comprehensive set of tools for analyzing the phylogenetic and trait diversity of ecological communities. The package calculates phylogenetic diversity metrics, performs trait comparative analyses, manipulates phenotypic and phylogenetic data, and performs tests for phylogenetic signal in trait distributions, community structure and species interactions. Picante is a package for the R statistical language and environment written in R and C, released under a GPL v2 open-source license, and freely available on the web (http://picante.r-forge.r-project.org) and from CRAN (http://cran.r-project.org).


Audit of referral of obstetric emergencies in Angola: a tool for assessing quality of care.
By auditing various aspects of referrals of obstetric emergencies, we wanted to study the effectiveness over time of a recently established network of peripheral birth units and two central hospitals in Luanda. 157 women referred for obstetric emergencies were studied regarding clinical outcome and process indicators like waiting time, partogramme quality and Caesarean section rate (CSR). After a change in routines at hospital admission and further partogramme education 92 referred women were compared with the former. Maternal mortality decreased from 17.8% to nil in the second. Total mean waiting time was reduced from 13.7 hours to 1.2 hours. Partogramme quality was significantly improved. CSR increased from 13 to 30%. Prolonged labour was the most common diagnosis.This study demonstrates the importance of clinic-based audit to enhance quality of care regarding referrals of patients with obstetric emergencies.


Mechanistic Challenges and Advantages of Biosensor Miniaturization into the Nanoscale.
Over the past few decades, there has been tremendous interest in developing biosensing systems that combine high sensitivity and specificity with rapid sample-to-answer times, portability, low-cost operation, and ease-of-use. Miniaturizing the biosensor dimensions into the nanoscale has been identified as a strategy for addressing the functional requirements of point-of-care and wearable biosensors. However, it is important to consider that decreasing the critical dimensions of biosensing elements impacts the two most important performance metrics of biosensors: limit-of-detection and response time. Miniaturization into the nanoscale enhances signal-to-noise-ratio by increasing the signal density (signal/geometric surface area) and reducing background signals. However, there is a trade-off between the enhanced signal transduction efficiency and the longer time it takes to collect target analytes on sensor surfaces due to the increase in mass transport times. By carefully considering the signal transduction mechanisms and reaction-transport kinetics governing different classes of biosensors, it is possible to develop structure-level and device-level strategies for leveraging miniaturization toward creating biosensors that combine low limit-of-detection with rapid response times.


Structural organization and biological activity of molecular clones of the integrated genome of a BALB/c mouse sarcoma virus.
BALB/c mouse sarcoma virus (BALB-MSV) is a spontaneously occurring transforming retrovirus of mouse origin. The integrated form of the viral genome was cloned from the DNA of a BALB-MSV-transformed nonproducer NRK cell line in the Charon 9 strain of bacteriophage lambda. In transfection assays, the 19-kilobase-pair (kbp) recombinant DNA clone transformed NIH/3T3 mouse cells with an efficiency of 3 X 10(4) focus-forming units per pmol. Such transformants possessed typical BALB-MSV morphology and released BALB-MSV after helper virus superinfection. A 6.8-kbp DNA segment within the 19-kbp DNA possessed restriction enzyme sites identical to those of the linear BALB-MSV genome. Long terminal repeats of approximately 0.6 kbp were localized at either end of the viral genome by the presence of a repeated constellation of restriction sites and by hybridization of segments containing these sites with nick-translated Moloney murine leukemia virus long terminal repeat DNA. A continuous segment of at least 0.6 and no more than 0.9 kbp of helper virus-unrelated sequences was localized toward the 3' end of the viral genome in relation to viral RNA. A probe composed of these sequences detected six EcoRI-generated DNA bands in normal mouse cell DNA as well as a smaller number of bands in rat and human DNAs. These studies demonstrate that BALB-MSV, like previously characterized avian and mammalian transforming retroviruses, arose by recombination of a type C helper virus with a well-conserved cellular gene.


Desacyl ghrelin prevents doxorubicin-induced myocardial fibrosis and apoptosis via the GHSR-independent pathway.
Doxorubicin is an effective chemotherapeutic agent used to treat malignancies, but it causes cardiomyopathy. Preliminary evidence suggests that desacyl ghrelin might have protective effects on doxorubicin cardiotoxicity. This study examined the cellular effects of desacyl ghrelin on myocardial fibrosis and apoptosis in a doxorubicin cardiomyopathy experimental model. Adult C57BL/6 mice received an intraperitoneal injection of doxorubicin to induce cardiomyopathy, followed by 4-day treatment of saline (control) or desacyl ghrelin with or without [d-Lys3]-GHRP-6 (a growth hormone secretagogue receptor or GHSR1a antagonist). Ventricular structural and functional parameters were evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in ventricular muscle to examine myocardial fibrosis and apoptosis. Cardiac dysfunction was induced by doxorubicin, as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This doxorubicin-induced cardiac dysfunction was prevented by the treatment of desacyl ghrelin no matter with or without the presence of [d-Lys3]-GHRP-6. Doxorubicin induced fibrosis (accumulated collagen deposition and increased CTGF), activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation, and caspase-3 activity and decreased Bcl-2/Bax ratio), and suppressed phosphorylation status of prosurvival signals (ERK1/2 and Akt) in ventricular muscles. All these molecular and cellular alterations induced by doxorubicin were not found in the animals treated with desacyl ghrelin. Notably, the changes in the major markers of apoptosis, fibrosis, and Akt phosphorylation were found to be similar in the animals following the treatment of desacyl ghrelin with and without GHSR antagonist [d-Lys3]-GHRP-6. These findings demonstrate clearly that desacyl ghrelin protects the cardiomyocytes against the doxorubicin-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through GHSR-independent mechanism.


Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study).
To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Retrospective, multicentre, non-randomised, observational study. Nationwide registry data in Japan. A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease.


Early patterns of gene expression correlate with the humoral immune response to influenza vaccination in humans.
Annual vaccination is the primary means for preventing influenza. However, great interindividual variability exists in vaccine responses, the cellular events that take place in vivo after vaccination are poorly understood, and appropriate biomarkers for vaccine responsiveness have not been developed. We immunized a cohort of healthy male adults with a licensed trivalent influenza vaccine and performed a timed assessment of global gene expression before and after vaccination. We analyzed the relationship between gene expression patterns and the humoral immune response to vaccination. Marked up regulation of expression of genes involved in interferon signaling, positive IL-6 regulation, and antigen processing and presentation, were detected within 24 hours of immunization. The late vaccine response showed a transcriptional pattern suggestive of increased protein biosynthesis and cellular proliferation. Integrative analyses revealed a 494-gene expression signature--including STAT1, CD74, and E2F2--which strongly correlates with the magnitude of the antibody response. High vaccine responder status correlates with increased early expression of interferon signaling and antigen processing and presentation genes. The results highlight the role of a systems biology approach in understanding the molecular events that take place in vivo after influenza vaccination and in the development of better predictors of vaccine responsiveness.


Hyperostotic Esthesioneuroblastoma.
Esthesioneuroblastomas are rare, soft-tissue tumors that can often extend from the sinonasal cavity into the intracranial and orbital space. Prognosis depends upon the histological grade and location/extent of the tumor. Treatment often consists of maximum surgical resection followed by adjuvant chemoradiation therapy. We present a case of a patient with esthesioneuroblastoma accompanied by an extensive osteoblastic reaction leading to significant hyperostosis along the skull base. His presenting symptoms included diplopia, and imaging revealed invasion of the orbital and intracranial spaces. Although a gross total resection of the soft tissue component of the tumor was achieved, a complete removal of the involved hyperostotic skull base could not be performed despite endoscopic endonasal and bifrontal craniotomy approaches in the same operative setting. Symptomatically, the patient improved and went on to receive chemoradiation therapy; he remains clinically and radiographically stable at 12 months. Investigation into the genetics and immunohistochemistry of this rare, hyperostotic variant of estheioneuroblastoma may provide details regarding its aggressive nature.


Assessment of bruxism in the clinic.
Bruxism is a much-discussed clinical issue in dentistry. Although bruxism is not a life-threatening disorder, it can influence the quality of human life, especially through dental problems, such as tooth wear, frequent fractures of dental restorations and pain in the oro-facial region. Therefore, various clinical methods have been devised to assess bruxism over the last 70 years. This paper reviews the assessment of bruxism, provides information on various assessment methods which are available in clinical situations and discusses their effectiveness and usefulness. Currently, there is no definitive method for assessing bruxism clinically that has reasonable diagnostic and technical validity, affects therapeutic decisions and is cost effective. One future direction is to refine questionnaire items and clinical examination because they are the easiest to apply in everyday practice. Another possible direction is to establish a method that can measure actual bruxism activity directly using a device that can be applied to patients routinely. More clinical studies should examine the clinical impact of bruxism on oral structures, treatment success and the factors influencing the decision-making process in dental treatment.


Combination Topical Chemotherapy for the Treatment of an Invasive Cutaneous Squamous Cell Carcinoma
Introduction: Standard of care for squamous cell carcinoma (SCC) is usually surgical, with either excision or Mohs micrographic surgery. However, surgery may not be ideal for elderly patients with numerous lesions, who are poor surgical candidates or who refuse surgery. Topical 5-fluorouracil (5-FU) and imiquimod have been studied off-label as monotherapies in the treatment of SCC in situ with promising results. However, long-term tumor-free survival rates are still less than with surgical management. Methods: We report a case of biopsy-proven invasive SCC in an 86-year-old Caucasian male with history of multiple actinic keratoses and no previous skin cancers. The patient declined surgical treatment due to concerns about cosmetic outcomes. A combination of topical 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream was used five nights per week under occlusion for a treatment goal of 30 total applications. The patient was evaluated in clinic every 2 weeks during which the site was treated with cryotherapy. The patient reported burning pain associated with treatment and only completed 24 of the 30 applications. Results: Follow-up biopsy 15 months after completing topical treatment revealed dermal scar with no evidence of residual carcinoma. Conclusion: Topical combination therapy with imiquimod, 5-FU, and tretinoin with intermittent, brief cryotherapy effectively treated a small, invasive SCC in this select patient who deferred surgery. Prospective randomized-controlled clinical trials to assess the role of combination topical treatment for invasive SCCs are warranted. J Drugs Dermatol. 2020;19(2)202-204. doi:10.36849/JDD.2020.2228


Coordinated tether formation in anatomically distinct mice growth centers is dependent on a functional vitamin D receptor and is tightly linked to three-dimensional tissue morphology.
Bone bridges linking the epiphysis and metaphysis termed "tethers" have been found in the femoral growth plates of C57Bl/6 mice and are disrupted when the vitamin D receptor (VDR) is ablated. It is unknown if tethers are found in other growth centers, if they are regulated in a comparable manner, or if they have a functional role in skeletal development or stability. To address this, distal femoral growth plates (GPs) and spheno-occipital synchondroses (SOSs) of wild-type C57Bl/6 mice from 2 to 15 weeks of age were analyzed using μCT scans. The GPs and SOSs of VDR+/+ and VDR-/- mice fed regular or rescue diets to restore mineral homeostasis until 10 weeks of age were also scanned. Tethers in GPs and SOSs both thickened and accumulated in number as these growth centers decreased in size. Ablating the VDR made GPs and SOSs rachitic and nearly eliminated tether formation. Rescue diets restored the volume of both growth centers but only partially restored growth center thickness and tether formation, suggesting that lα,25-dihydroxy vitamin D(3) partially regulates tether formation in these growth centers via its receptor. In VDR+/+ mice 2-15 weeks in age, growth center thickness was inversely correlated to animal weight whereas tether phenotype (tether volume/growth center volume, tether number/mm, tether width, tether spacing) was significantly related to animal weight. In both 2-15 week old VDR+/+ and 10 week old VDR+/+ and VDR-/- mice on normal and rescue diets, tether phenotype (tether number/mm, tether spacing) had strikingly similar relationships to growth center thickness. These results show that tethers are present in growth centers in different anatomic and undergo developmental changes in a comparable manner; in both sites, VDR-regulated tether formation is strongly linked to growth center morphology; and tether formation is associated with body weight, suggesting a role in maintaining growth plate stability during growth.


Mapping propagation of mechanical activation in the paced heart with MRI tagging.
The temporal evolution of three-dimensional (3-D) strain maps derived from magnetic resonance imaging (MRI) tagging were used to noninvasively evaluate mechanical activation in the left ventricle (LV) while seven canine hearts were paced in situ from three different sites: the base of the LV free wall (LVb), the right ventricular apex (RVa), and the right atrium (RA). Strain maps plotted against time showed the evolution of shortening over the entire LV midwall and were used to generate mechanical activation maps showing the onset of circumferential shortening. RA pacing showed rapid synchronous shortening; LVb pacing showed a wave front of mechanical activation propagating slowly and steadily from the pacing site, whereas RVa pacing showed regions of rapid and slower propagation. The mechanical (M) activation times correlated linearly with the electrical (E) activation (M = 1.06E + 8.4 ms, R = 0.95). The time for 90% activation of the LV was 63.1 +/- 24.3 ms for RA pacing, 130.2 +/- 9.8 ms for LVb pacing, and 121.3 +/- 17.9 ms for RVa pacing. The velocity of mechanical activation was calculated for LVb and RVa pacing and was similar to values reported for electrical conduction in myocardium. The propagation of mechanical activation for RVa pacing showed regional variations, whereas LVb pacing did not.


Identifying barriers to the application of evidence based practice in mental health nursing.
Although contemporary nursing literature urges clinicians to embrace the principles of evidence-based practice and utilise research to guide professional activity, this challenge has frequently gone unheeded by mental health nurses. Indeed the reality of merging research and practice is a complex process impeded by significant barriers. Examination of these barriers provides credible reasonfor mental health nurses' slow progress toward evidence-based nursing practice to date. However, exploration of these barriers also leads to the identification of strategies to overcome them, inevitably rendering the current situation untenable.