A preliminary descriptive report of the longevity of the effects of Swedish Massage therapy for subjects with Generalized Anxiety Disorder.
Generalized Anxiety Disorder (GAD) is a prevalent and costly disorder, and many patients may prefer non-traditional treatment. A proof-of-concept study demonstrated the efficacy of Swedish Massage Therapy (SMT) as a monotherapy for treatment of GAD. Subjects were followed-up 6-12 months after study completion to evaluate post-treatment outcome. Subjects were enrolled into a randomized, single-masked clinical trial between March of 2012 and May of 2013. Forty-seven untreated subjects with DSM-IV diagnosis of GAD were randomly assigned to 6 weeks of twice-a-week light touch (LT) followed by 6 weeks of twice-a-week SMT, or 12 weeks of twice-a-week SMT. The primary outcome measure was reduction in Hamilton Anxiety Rating Scale (HAM-A) scores after six weeks of SMT versus LT. Qualifying participants received a follow-up survey to investigate whether the benefits of SMT for GAD were sustained. 28 of 40 subjects completed at least 12 sessions of SMT and were sent the follow-up survey. Of the 19 subjects with follow-up, nine (47%) reported no return of GAD symptoms up to 1 year after study completion. There were no differences between those randomized to 12 weeks SMT and those receiving 6 weeks LT followed by 6 weeks SMT. Of those reporting a return of some symptoms, 50% associated symptom return with a stressful life event. In this first monotherapy trial of SMT for the treatment of GAD, follow-up results suggest that the beneficial effects of SMT may last up to 1 year after end of treatment.


Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis.
Eosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers.


Genomic Scan for Selection Signature Reveals Fat Deposition in Chinese Indigenous Sheep with Extreme Tail Types.
It is a unique feature that fat can be deposited in sheep tails and rumps. To elucidate the genetic mechanism underlying this trait, we collected 120 individuals from three Chinese indigenous sheep breeds with extreme tail types, namely large fat-tailed sheep (n = 40), Altay sheep (n = 40), and Tibetan sheep (n = 40), and genotyped them using the Ovine Infinium HD SNP BeadChip. Then genomic scan for selection signatures was performed using the hapFLK. In total, we identified 25 genomic regions exhibiting evidence of having been under selection. Bioinformatic analysis of the genomic regions showed that selection signatures related to multiple candidate genes had a demonstrated role in phenotypic variation. Nine genes have documented association with sheep tail types, including WDR92, TBX12, WARS2, BMP2, VEGFA, PDGFD, HOXA10, ALX4, and ETAA1. Moreover, a number of genes were of particular interest, including RXFP2 associated with the presence/absence and morphology of horns; MITF involved in coat color; LIN52 and SYNDIG1L related to the number of teats; MSRB3 gene associated with ear sizes; LTBP2 considered as a positional candidate genes for number of ribs; JAZF1 regulating lipid metabolism; PGRMC2, SPAG17, TSHR, GTF2A1, and LARP1B implicated with reproductive traits. Our findings provide insights into fat tail formation and a reference for carrying out molecular breeding and conservation in sheep.


Neonatal hyperthyroidism in the rat produces an increase in the activity of microperoxisomal marker enzymes coincident with biochemical signs of accelerated myelination.
The effect of neonatal hyperthyroidism produced by injection of tri-iodothyronine (T3) on myelination and on the microperoxisomal population of the brain was studied in young rats. Data on the lipid composition of myelin show that myelinogenesis starts earlier in treated animals. In coincidence with the early appearance of myelin, there is an increase in the population of brain microperoxisomes, indicated by the increase in the activity of two enzymes that have been shown to be located in these organelles: catalase and acyl CoA-dihydroxyacetone phosphate acyl transferase. Double-label experiments using (1,2,3-3H) and (2-3H) glycerol to study the synthesis of glycerophospholipids through the dihydroxyacetone phosphate (DHAP) pathway give further support to the above-mentioned findings and suggest that there is an active participation of microperoxisomes in the synthesis of myelin lipids during the period of myelin formation.


The role of glial cells in multiple sclerosis disease progression.
Despite the development of highly effective treatments for relapsing-remitting multiple sclerosis (MS), limited progress has been made in addressing primary progressive or secondary progressive MS, both of which lead to loss of oligodendrocytes and neurons and axons, and to irreversible accumulation of disability. Neuroinflammation is central to all forms of MS. The current effective therapies for relapsing-remitting MS target the peripheral immune system; these treatments, however, have repeatedly failed in progressive MS. Greater understanding of inflammation driven by CNS-resident cells - including astrocytes and microglia - is, therefore, required to identify novel potential therapeutic opportunities. Advances in imaging, biomarker analysis and genomics suggest that microglia and astrocytes have central roles in the progressive disease process. In this Review, we provide an overview of the involvement of astrocytes and microglia at major sites of pathology in progressive MS. We discuss current and future therapeutic approaches to directly target glial cells, either to inhibit pathogenic functions or to restore homeostatic functions lost during the course of the disease. We also discuss how bidirectional communication between astrocytes and microglia needs to be considered, as therapeutic targeting of one is likely to alter the functions of the other.


Isradipine versus captopril in patients with essential hypertension.
We conducted a double-blind, crossover study comparing the antihypertensive effects of isradipine versus captopril in patients with essential hypertension. Seventeen patients (8 men, 9 women; 6 whites, 11 blacks) completed both phases of the study, which consisted of two 5-week treatment periods separated by 2 weeks of placebo treatment. Each drug was randomly allocated to half the patients as the first drug and half as the second drug they received. Ambulatory blood pressure (BP) monitoring was carried out on the day before treatment and the last day of each active treatment. Both drugs were effective and well tolerated but isradipine was more effective overall than captopril in lowering BP (9.4% vs 3.9%, respectively; P < 0.02). Black patients had significantly higher BP at baseline than white patients; furthermore, black patients responded better to isradipine than to captopril. White patients had a smaller decrease in blood pressure with both drugs than did black patients, but white patients still attained a lower diastolic BP with captopril than did black patients (88 +/- 2 mm Hg vs 96 +/- 9 mm Hg; P < 0.01). There was no correlation between the pretreatment plasma levels of pressor hormones (plasma renin activity, catecholamines, and arginine vasopressin) and the magnitude of BP response to either drug, but the decrease in BP in response to captopril correlated significantly with the increase in plasma renin activity during treatment (r = -.84; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Desmoid tumor presenting as a superior sulcus tumor: a unique bone change in the vertebral body.
Desmoid tumor, also referred to as aggressive fibromatosis, is a relatively rare, locally infiltrative, histologically benign tumor. This report details a case of desmoid tumor presented as a superior sulcus tumor, which showed a unique manifestation in the vertebral bodies on computed tomography.


Bactericidal catechins damage the lipid bilayer.
The mode of antibacterial action of, the green tea (Camellia sinensis) extracts, (-)-epigallocatechin gallate (EGCg) and (-)-epicatechin (EC) was investigated. Strong bactericidal EGCg caused leakage of 5,6-carboxyfluorescein from phosphatidylcholine liposomes (PC), but EC with very weak bactericidal activity caused little damage to the membrane. Phosphatidylserine and dicetyl phosphate partially protected the membrane from EGCg-mediated damage when reconstituted into the liposome membrane with PC. EGCg, but not EC, caused strong aggregation and NPN-fluorescence quenching of PC-liposomes and these actions were markedly lowered in the presence of negatively charged lipids. These results show that bactericidal catechins primarily act on and damage bacterial membranes. The observation that Gram-negative bacteria are more resistant to bactericidal catechins than Gram-positive bacteria can be explained to some extent by the presence of negatively charged lipopolysaccharide.


Evaluation of two intensive care delirium screening tools for non-critically ill hospitalized patients.
Delirium is a common, yet frequently under-recognized medical/psychiatric complication for hospitalized patients, associated with substantial morbidity and mortality. While easy-to-use delirium screening tools exist for ventilated patients, their use in non-critically ill, hospitalized patients has not been validated. This prospective 4-week comparison of daily delirium status, using screening tools (Confusion Assessment Method for the Intensive Care Unit [CAM-ICU] and Intensive Care Delirium Screening Checklist [ICDSC]) vs. a daily neuropsychiatric examination as a reference standard, was conducted in 139 inpatients in two medical oncology units at a large teaching hospital during July, 2009. Based on neuropsychiatric examination, 36 (26%) patients had at least 1 day of delirium during their hospital admission. For 21 (15%) patients, delirium was present at the initial assessment, while 15 (11%) developed delirium at a median (IQR) of three (2-7) subsequent assessments. Delirium was present on 20% of all patient-days. For the initial evaluation, the CAM-ICU had a sensitivity of 18% (95% confidence interval [CI], 5%-44%), and a sensitivity of 18% (9% -32%) when using all assessments, adjusting for repeated measures on each patient. The ICDSC had sensitivities of 47% (24%-72%) and 62% (49%-74%). The specificity of both instruments was very high (≥98%). This study suggests that in non-critically ill hospitalized patients, the CAM-ICU and ICDSC intensive care delirium screening tools are not adequately sensitive for use in routine clinical practice. Further work is needed to develop more sensitive, efficient tools in this population.


Correction to: Role of microRNAs in host defense against Echinococcus granulosus infection: a preliminary assessment.
The published article unfortunately contained mistake. After replacing the image from colored version to black and white, the Fig. 1 caption, unfortunately, was left unupdated.


Particle clearance from the canine pleural space into thoracic lymph nodes: an experimental study.
We instilled tungsten powder (CaWO4) into the pleural space of the dog and studied the kinetics and distribution of particle translocation from the pleural space to the thoracic lymph nodes over 1-7 days. We found that the transport of tungsten particles to regional lymph nodes was present at day 1, and reached its peak at day 3. In situ detection of tungsten by elemental particle analysis of lymph node sections by scanning electron microscopy complemented by light microscopy and X-ray analysis allowed precise mapping of the marker in the thoracic nodes. The first lymph nodes to become tungsten-laden was the parasternal group (day 1-3). From day 3 to 7 tungsten inclusions decreased in these parasternal nodes while moderately increasing in the remaining intrathoracic lymph nodes. Retrocardiac pleural folds containing numerous "milky spots" also accumulated prominent amounts of tungsten early after intrapleural injection of CaWO4. These data indicate that 1) particle translocation from the pleural space to regional lymph nodes is a rapid process and is first directed to the parasternal lymph nodal subgroup; 2) particle dissemination to virtually all other lymph nodes within the thorax follows thereafter; 3) retrocardiac pleural folds contribute to the clearance of particles from the pleural space.


Compressibilities and volume fluctuations of archaeal tetraether liposomes.
Bipolar tetraether lipids (BTLs) are abundant in crenarchaeota, which thrive in both thermophilic and nonthermophilic environments, with wide-ranging growth temperatures (4-108°C). BTL liposomes can serve as membrane models to explore the role of BTLs in the thermal stability of the plasma membrane of crenarchaeota. In this study, we focus on the liposomes made of the polar lipid fraction E (PLFE). PLFE is one of the main BTLs isolated from the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. Using molecular acoustics (ultrasound velocimetry and densimetry), pressure perturbation calorimetry, and differential scanning calorimetry, we have determined partial specific adiabatic and isothermal compressibility, their respective compressibility coefficients, partial specific volume, and relative volume fluctuations of PLFE large unilamellar vesicles (LUVs) over a wide range of temperatures (20-85°C). The results are compared with those obtained from liposomes made of dipalmitoyl-L-α-phosphatidylcholine (DPPC), a conventional monopolar diester lipid. We found that, in the entire temperature range examined, compressibilities of PLFE LUVs are low, comparable to those found in gel state of DPPC. Relative volume fluctuations of PLFE LUVs at any given temperature examined are 1.6-2.2 times more damped than those found in DPPC LUVs. Both compressibilities and relative volume fluctuations in PLFE LUVs are much less temperature-sensitive than those in DPPC liposomes. The isothermal compressibility coefficient (β(T)(lipid)) of PLFE LUVs changes from 3.59 × 10(-10) Pa(-1) at 25°C to 4.08 × 10(-10) Pa(-1) at 78°C. Volume fluctuations of PLFE LUVs change only 0.25% from 30°C to 80°C. The highly damped volume fluctuations and their low temperature sensitivity, echo that PLFE liposomes are rigid and tightly packed. To our knowledge, the data provide a deeper understanding of lipid packing in PLFE liposomes than has been previously reported, as well as a molecular explanation for the low solute permeation and limited membrane lateral motion. The obtained results may help to establish new strategies for rational design of stable BTL-based liposomes for drug/vaccine delivery.


Quantitative evaluation of gait features after total knee arthroplasty: Comparison with age and sex-matched controls.
Gait function after total knee arthroplasty (TKA) is suboptimal. However, quantified analysis with comparing a control group is lacking. The aims of this study were 1) to compare the gait before and after TKA and 2) to compare postoperative gait to that of an age-sex matched control group. This study consisted of 46 female and 38 male patients with end-stage knee osteoarthritis who underwent bilateral TKA, and 84 age- and sex-matched controls without knee pain and osteoarthritis. Seven gait parameters, including lower extremity alignment, knee adduction moment (KAM), knee flexion angle, external knee flexion moment, hip adduction angle, external hip adduction moment, and the varus-valgus arc during the stance phase, were collected using a commercial opto-electric gait analysis system. Principal component analysis was used for data processing and the standardized mean differences (SMDs) of the principal component scores were compared. The most significant gait change after TKA was the alignment (SMD 1.62, p < 0.001). The average stance phase alignment changed from varus 7.3° to valgus 0.5°. The second significant change was a decrease of the KAM (SMD 1.08, p < 0.001). These two features were closely correlated (r = 0.644, p < 0.001). The gait feature that differed most from the controls was the varus-valgus arc during the stance phase (SMD 1.68, p < 0.001), which was constrained by 31% after TKA (p < 0.001) and was only 37% compared to the controls (p < 0.001). Improvement in gait after TKA was obtained through alignment correction. However, TKA significantly constrained coronal knee motion. TKA improved gait suboptimally; the gait was significantly different from that of controls.


A new technique in independent intermittent catheterization: the Mitrofanoff catheterizable channel.
The Mitrofanoff continent catheterizable channel is a surgical option that gives rehabilitation patients who have difficulty gaining access to their urethras for clean intermittent catheterization more independence in selfcare. This article presents a historical review, pre- and postoperative nursing assessment, nursing care, and a case study.


Corticotropin-releasing factor receptors: autoradiographic identification.
Our studies on CRF receptors confirm the established role of CRF in regulating pituitary hormone secretion and support a physiological role for endogenous CRF in regulating CNS activity. Studies to characterize CRF receptors and CRF-containing pathways in the brain provide a means for understanding the various functions of this neuropeptide in different areas of the CNS. Finally, the ability to identify and localize CRF receptors in postmorten human tissue provides a basis for studying the role of CRF in the etiology and pathophysiology of a variety of endocrine, neurological, and psychiatric disorders.


A survey of non-sedate practices when acquiring pediatric magnetic resonance imaging examinations.
Improving access to magnetic resonance imaging (MRI) in childhood can be facilitated by making it faster and cheaper and reducing need for sedation or general anesthesia (GA) to mitigate motion. Some children achieve diagnostic quality MRI without GA through the use of non- practices fostering their cooperation and/or alleviating anxiety. Employed before and during MRI, these variably educate, distract, and/or desensitize patients to this environment. To assess current utilization of non-sedate practices in pediatric MRI, including variations in practice and outcomes. A survey-based study was conducted with 1372 surveys emailed to the Society for Pediatric Radiology members in February 2021, inviting one response per institution. Responses from 50 unique institutions in nine countries revealed 49/50 (98%) sites used ≥ 1 non-sedate practice, 48/50 (96%) sites in infants < 6 months, and 11/50 (22%) for children aged 6 months to 3 years. Non-sedate practices per site averaged 4.5 (range 0-10), feed and swaddle used at 47/49 (96%) sites, and child life specialists at 35/49 (71%). Average success rates were moderate (> 50-75%) across all sites and high (> 75-100%) for 20% of sites, varying with specific techniques. Commonest barriers to use were scheduling conflicts and limited knowledge. Non-sedate practice utilization in pediatric MRI was near-universal but widely variable across sites, ages, and locales, with room for broader adoption. Although on average non-sedate practice success rates were similar, the range in use and outcomes suggest a need for standardized implementation guidelines, including patient selection and outcome metrics, to optimize utilization and inform educational initiatives.


Driving simulator sickness: an evidence-based review of the literature.
Guided by the Occupational Therapy Practice Framework: Domain and Process (2nd edition; American Occupational Therapy Association, 2008), we conducted an evidence-based review on simulator sickness (SS). We searched Web of Science, PubMed, SafetyLit, Google Scholar, and recently published literature. We used the American Academy of Neurology's classification criteria to extract data from 10 studies and assign each a level of 1-4, with "1" indicating the highest level of evidence. We grouped studies that addressed SS into client factors, context and environment factors, and activity demands. Client factors (i.e., older clients [>70 yr; Level B], women [Level B]) and context/environment factors (e.g., refresh rates, scenario design and duration, simulator configuration, and calibration; Level B) probably increase the rates of SS, whereas activity demands (vection, speed of driving, and postural instability; Level C) possibly contribute to SS. We classified factors contributing to SS and identified the need for randomized trials to identify causes of SS.


The risk of transmitting prion disease by blood or plasma products.
Various experimental studies have shown infectivity in blood in relation to bovine spongiform encephalitis (BSE) and variant Creutzfeldt-Jakob disease (vCJD). Human to human transmission vCJD infection has been reported via transfusion of non-leukocyte-reduced red cells and, probably, via factor VIII concentrates. A number of precautionary measures are in place but uncertainties remain, especially concerning the number of BSE-infected people in the population. Additional measures such as prion filtration need consideration.


Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials.
In the era of immunotherapy, it is still unclear which is the best first-line therapy for patients with oncogenic driver negative advanced non-squamous non-small cell lung cancer (NS-NSCLC) who cannot tolerate immunotherapy, or subsequent therapy for patients with oncogenic driver positive NS-NSCLC whose disease progressed on prior targeted therapy. To assess the optimal choice of first-line and maintenance treatment regimens, we performed a meta-analysis of prospective randomized controlled clinical trials (RCTs) of patients with NS-NSCLC on bevacizumab combined with chemotherapy. All eligible RCTs comparing pemetrexed-platinum with or without bevacizumab (PP ± B) and paclitaxel-carboplatin with bevacizumab (PC + B) as a first-line therapy, or comparing bevacizumab plus pemetrexed (Pem + B) and bevacizumab alone (B) as a maintenance treatment for advanced NS-NSCLC, were included after systematically searching web databases and meeting abstracts. The main research endpoints were comparisons of overall survival (OS) and progression-free survival (PFS). The other endpoints were objective response rate (ORR), 1-year PFS rate (PFSR1y) and major grade 3/4 treatment-related adverse events. Data of 3139 patients from six RCTs were incorporated into analyses. Three RCTs were included in an analysis that compared PP ± B and PC + B as a first-line therapy for advanced NS-NSCLC. Patients treated with first-line PP ± B showed similar OS and ORR, but significantly improved PFS (hazard ratio [HR], 0.88) and PFSR1y (risk ratio [RR], 0.83), as compared to patients treated with PC + B (all P < 0.05). PP ± B resulted in higher rates of grade 3/4 anemia and thrombocytopenia, but lower rates of neutropenia, febrile neutropenia, and sensory neuropathy than PC + B (all P < 0.001). The other three RCTs were included in an analysis that compared Pem + B and B as a maintenance treatment. Compared with B, Pem + B maintenance treatment resulted in significant improvements in OS (HR, 0.88), PFS (HR, 0.64), and PFSR1y (RR, 0.70), but higher rates of anemia, thrombocytopenia, and neutropenia (all P < 0.001). Although the first-line PP + B regimen had longer PFS and PFSR1y than the PC + B regimen, no OS difference was observed. Addition of pemetrexed to bevacizumab as maintenance therapy significantly improved OS compared with bevacizumab maintenance alone, but led to more toxicity.


Humboldt's enigma: What causes global patterns of mountain biodiversity?
Mountains contribute disproportionately to the terrestrial biodiversity of Earth, especially in the tropics, where they host hotspots of extraordinary and puzzling richness. With about 25% of all land area, mountain regions are home to more than 85% of the world's species of amphibians, birds, and mammals, many entirely restricted to mountains. Biodiversity varies markedly among these regions. Together with the extreme species richness of some tropical mountains, this variation has proven challenging to explain under traditional climatic hypotheses. However, the complex climatic characteristics of rugged mountain regions differ fundamentally from those of lowland regions, likely playing a key role in generating and maintaining diversity. With ongoing global changes in climate and land use, the role of mountains as refugia for biodiversity may well come under threat.


pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-alpha in breast cancer.
The estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription in a physiological setting. These findings suggest that pRb2/p130-multimolecular complexes can be key elements in the regulation of ER-alpha gene expression and may be viewed as promising targets for the development of novel therapeutic strategies in the treatment of breast cancer, especially for those tumors that are ER negative.


Interaction of subpopulations of murine lymph node lymphocytes in antigen-induced [14C]-thymidine incorporation: T and B cell synergy in the response to antigen.
The antigen-induced [14C]-thymidine incorporation of murine lymph node cells (LNC) that were non-adherent (NAD) or adherent (AD) to nylon wool was studied. In contrast to NAD-LNC, AD-LNC responded like unfractionated LNC, and these responses were T lymphocyte dependent. By co-culturing NAD-LNC with subpopulations of AD-LNC the cellular requirements and interactions necessary for maximal incorporation of [14C]-thymidine were determined. A synergistic effect was observed when NAD-LNC and AD-LNC were co-cultured. Synergism was not dependent on T lymphocytes or macrophages in the AD-LNC population but was associated with the B lymphocyte subpopulation. These results indicate that the number of B lymphocytes present in a population of LNC can significantly influence the magnitude of the response to antigen.


The efficacy of mitral valve surgery in children with dilated cardiomyopathy and severe mitral regurgitation.
Severe mitral regurgitation predicts poor outcomes in adults with left ventricular dysfunction. Frequently, adult patients now undergo initial mitral valve surgery instead of heart transplant. Pediatric data are limited. This study evaluates the efficacy of mitral valve surgery for severe mitral regurgitation in children with dilated cardiomyopathy. This is a single-institution experience in seven children (range, 0.5-10.9 years) with severe mitral regurgitation and dilated cardiomyopathy who underwent mitral valve surgery between January 1988 and February 2005, with follow-up to January 2006. Children with dilated cardiomyopathy had a depressed fractional shortening preoperatively (24.4% +/- 6.1%) that remained depressed (22.9% +/- 7.6%) 1.3 +/- 1.2 years after surgery (p = 0.50). Left ventricular end-diastolic (6.5 +/- 1.5 to 4.8 +/- 1.8 z-scores, p < 0.01) and end-systolic (6.8 +/- 1.5 to 5.5 +/- 2.1 z-scores, p < 0.05) dimensions improved. Hospitalization frequency had a median decrease of 6.0 hospitalizations per year (p < 0.02). Three patients were transplanted 0.2, 2.4, and 3.5 years after surgery. There was no perioperative mortality. Mitral valve surgery in children with dilated cardiomyopathy was performed safely and improved symptoms, stabilizing ventricular dysfunction in most patients. Mitral valve surgery should be considered prior to heart transplant in children with dilated cardiomyopathy and severe mitral regurgitation.


Effect of aminooxyacetic acid on extracellular level of D-serine in rat striatum: an in vivo microdialysis study.
To elucidate the effect of an inhibitor of pyridoxal phosphate-dependent enzymes, aminooxyacetic acid, on the activity of serine racemase in vivo, we have investigated the effect of aminooxyacetic acid on the extracellular concentration of D-serine in the rat striatum using an in vivo microdialysis technique. The intrastriatal perfusion of aminooxyacetic acid caused a significant decline in the extracellular concentration of D-serine. These data, together with the fact that serine racemase is a pyridoxal phosphate-dependent enzyme, suggest that the aminooxyacetic acid-induced reduction of the extracellular D-serine may be at least in part due to the drug's ability to inhibit serine racemase.


Preliminary Study of Fear of Re-Injury following Sport-Related Concussion in High School Athletes.
The influence of fear of re-injury that this variable has on recovery outcomes following sports-related concussion remains unknown. We examined changes in fear of re-injury throughout concussion recovery, and compared changes in neurocognitive, symptom, vestibular/ocular motor, and recovery time outcomes between concussed adolescent athletes who endorsed high and low fear of re-injury. Individuals with high fear of re-injury were more symptomatic and more likely to exhibit vestibular/ocular motor symptoms over clinical cutoffs than those with low fear of re-injury. Recovery time was not significantly different between the groups. These findings may help explain performance on more subjective concussion assessments.


Validation of Malay Version of Snaith-Hamilton Pleasure Scale: Comparison between Depressed Patients and Healthy Subjects at an Out-Patient Clinic in Malaysia.
The Snaith-Hamilton Pleasure Scale (SHAPS) is a self-assessment scale designed to evaluate anhedonia in various psychiatric disorders. In order to facilitate its use in Malaysian settings, our current study aimed to examine the validity of a Malay-translated version of the SHAPS (SHAPS-M). In this cross-sectional study, a total of 44 depressed patients and 82 healthy subjects were recruited from a university out-patient clinic. All participants were given both the Malay and English versions of the SHAPS, Fawcett-Clark Pleasure Scale (FCPS), General Health Questionnaire 12 (GHQ-12), and the Beck Depression Inventory (BDI) to assess their hedonic state, general mental health condition and levels of depression. The results showed that the SHAPS-M has impressive internal consistency (α = 0.96), concurrent validity and good parallel-form reliability (intraclass coefficient, ICC = 0.65). In addition to demonstrating good psychometric properties, the SHAPS-M is easy to administer. Therefore, it is a valid, reliable, and suitable questionnaire for assessing anhedonia among depressed patients in Malaysia.


An Update on Aspirin for Cardioprevention: Implications for Patient Care.
The goal of this activity is to increase awareness among healthcare providers about the role of aspirin in the primary and secondary prevention of cardiovascular disease.


Can Bioactive Compounds in Beetroot/Carrot Juice Have a Neuroprotective Effect? Morphological Studies of Neurons Immunoreactive to Calretinin of the Rat Hippocampus after Exposure to Cadmium.
Cadmium ions (Cd2+) penetrate the blood-brain barrier and can, among other effects, influence intracellular calcium metabolism, leading to neurodegeneration. In the presented work, we estimated the effect of Cd2+ on the expression of calretinin in the neurons of the rat hippocampus and analyzed the reverse effect of freshly pressed beetroot/carrot juice in this context. In the 12-week lasting experiment, 32 8-week-old male Wistar rats were divided into four experimental groups (n = 8): the control group (C) received pure tap water; the Cd group (Cd)-received Cd2+ dissolved in tap water (5 mg Cd2+/kg b.w.); and two groups received beetroot/carrot juice: the BCJ group was administered only juice, and the Cd + BCJ group received juice with the addition of Cd2+ (5 mg Cd2+/kg b.w.). The exposition to low doses of Cd2+ caused a significant decrease in calretinin-immunoreactive (Cr-IR) neurons compared to the non-exposed groups. Moreover, the addition of Cd2+ to tap water reduced the numbers and length of Cr-IR nerve fibers. The negative effect of Cd2+ was significantly attenuated by the simultaneous supplementation of beetroot/carrot juice (Cd + BCJ). The study showed that the bioactive compounds in the beetroot/carrot juice can modulate Ca2+ levels in neurons, and thus, potentially act as a neuroprotective factor against neuronal damage.


Dichotic listening and otoacoustic emissions: shared variance between cochlear function and dichotic listening performance in adults with normal hearing.
The present study investigated a possible connection between speech processing and cochlear function. Twenty-two subjects with age range from 18 to 39, balanced for gender with normal hearing and without any known neurological condition, were tested with the dichotic listening (DL) test, in which listeners were asked to identify CV-syllables in a nonforced, and also attention-right, and attention-left condition. Transient evoked otoacoustic emissions (TEOAEs) were recorded for both ears, with and without the presentation of contralateral broadband noise. The main finding was a strong negative correlation between language laterality as measured with the dichotic listening task and of the TEOAE responses. The findings support a hypothesis of shared variance between central and peripheral auditory lateralities, and contribute to the attentional theory of auditory lateralization. The results have implications for the understanding of the cortico-fugal efferent control of cochlear activity.


Pressure ulcers in secondary care: incidence, prevalence, and relevance.
To compare point and period prevalence rates. Descriptive, cohort, cross-sectional survey. From a cohort of 25,075 cases, information on pressure ulcer status on admission was recorded for 20,283 cases. From 3237 selected cases, the pressure ulcer team made 2234 assessments. Point prevalence, period prevalence, and incidence rates. The cohort showed a period prevalence rate of 1.4% and an incidence rate of 0.6%. Patients with a pressure ulcer were older, were more likely to have had surgery, had longer hospital stays, and had a higher cost weight. The cross-sectional survey revealed a point prevalence rate of 5.3%. Patients within the cross-sectional survey had longer lengths of stay, were more likely to have had surgery, and presented a higher cost weight in comparison with the cohort. In an unselected hospital sample one can expect a period prevalence rate of 2% and a point prevalence rate of 10%. As demonstrated by the present study, differences between the 2 prevalence measurements are mainly due to the confounding of point prevalence rates by length of stay. Length of stay determines the probability of inclusion in a cross-sectional study and should be considered in pressure ulcer trials in the future.


Development of an iron(II)-catalyzed aerobic catechol cleavage and biomimetic synthesis of betanidin.
An aerobic iron(II)-catalyzed cleavage of catechols was developed. This reaction allows for the preparation of 2-methoxy-2 H-pyrans that can be employed as versatile building blocks for synthesis. The utility of this biomimetic oxidative cleavage is featured in the synthesis of betanidin, a natural colorant with antioxidant properties.


Comparison of strains produced by titanium and poly D, L-lactide Acid plating systems to in vitro forces.
To determine if a specific resorbable plating system provides similar fixation, in terms of strain distribution under load, to a titanium system when the Champy technique is applied for the treatment of a mandibular angle fracture. A formalin-fixed cadaver mandible was harvested just before the study. A bicortical osteotomy was then made using a diamond disc extending in an oblique direction in the area of the angle. It was then passively fixated with a 4-hole 2.0-mm miniplate. Two stacked rosette strain gauges were bonded to the mandible on either side of the fracture. Each rosette had 3 strain gauges arranged in specific degrees relative to each other. The mandible was then placed on a dynanometer and 30 lb loads were delivered on the ipsilateral molar. Static resistance was placed in the condylar neck region to simulate the glenoid fossa. Loading was repeated 10 times with a period of 3 minutes between loads. Measurements were recorded for each strain gauge after loads were in place for 30 seconds. The same process was repeated using a 4-hole 2.1-mm resorbable miniplate. The strains were then used to calculate the maximum and minimum strains for each rosette. Hooke's law was used to calculate the principal stresses. Differences were observed between the strain gauges for each individual plating system. There was variability within the resorbable plate measurements as shown by the standard deviation. Using the REML ANOVA test, a significant difference was found between the 2 materials. In this in vitro study, there were significant biomechanical differences observed between a 2.0-mm titanium miniplate and a 2.1-mm resorbable miniplate when used to treat a mandibular angle fracture following Champy's principles. Based on our finding, both systems cannot be used interchangeably for the treatment of mandibular angle fractures under the same clinical conditions.


Periodontal and Implant Radiology.
Dental radiography can be used to detect alveolar bone levels around periodontal and peri-implant structures. Periodontal radiographic images can assess alveolar bone height, periodontal ligament, furcation involvement, and evidence of bone destruction. Peri-implant radiographic images can assess the alveolar bone height in relation to the implant structure. As an adjunct to patient care, radiography can aid in the diagnosis of non-health.


Direct high-performance liquid chromatographic analysis of D-tocopheryl acid succinate and derivatives.
A method of analysis of a Vitamin E derivative D-tocopheryl acid succinate (TS) in biological fluids and commercially available products is necessary to study the kinetics of in vitro and in vivo metabolism, tissue distribution, and content uniformity. A simple and inexpensive high-performance liquid chromatographic method was developed for the direct determination of D-tocopheryl acid succinate in commercially available products, rat serum, and rat tissues. This method can also be applied to the determination of 15 Vitamin E derivatives. Rat serum (0.1 ml) was extracted with sodium dodecyl sulfate, ethanol, hexane, and then dried under nitrogen gas after addition of the internal standard, DL-alpha-tocopherol acetate. Separation was achieved on a C18 column with UV detection at 205 nm. The calibration curve for D-tocopheryl acid succinate was linear ranging from 0.025 to 100 microg/ml. The mean extraction efficiency was >92%. Precision of the assay was <5% (CV), and was within 5% at the limit of quantitation (0.025 microg/ml). Bias of the assay was lower than 5%, and was within 5% at the limit of quantitation. The assay was applied successfully to the serum and tissue distribution of D-tocopheryl acid succinate in rats, various Vitamin E derivatives, and content uniformity in commercially available products containing D-tocopheryl acid succinate.


Building concordant relationships with patients starting antidepressant medication.
Fifty one patients beginning courses of antidepressant medication were recruited from general practice surgeries in two health authorities in London and interviewed on two occasions. Respondents were asked about their experiences of using antidepressant medication, including their information needs and the level of involvement which they had had in making decisions about their medication. Analysis was carried out using qualitative procedures. The study identified information needs which were unmet at the start of treatment, including the impact of adverse drug reactions on patients' lives, the very gradual process of recovery and information regarding dosage prescribed in the context of minimum and maximum dosages. Respondents also had a broad view of the term dependency that needed to be addressed. However, some respondents reported that they experienced difficulty in absorbing information given during the initial consultation. Therefore developing strategies for reinforcement of information would be advantageous. Patients involvement in decision making varied between respondents and at different points in therapy.


Androgen insensitivity syndrome: a survey of diagnostic procedures and management in the UK.
A two year survey of androgen insensitivity syndrome (AIS) to assess current diagnostic and management strategies. Cases were ascertained by inclusion on the British Paediatric Surveillance Unit monthly report card for 24 months. Fifty one of 139 notifications were confirmed as AIS; 29 cases were complete AIS and 22 cases partial AIS. Seventy six per cent of complete AIS presented with an inguinal hernia, and half the complete AIS patients had an established family history of the disorder. Presentation in the partial AIS group was through ambiguous or undermasculinised genitalia; 59% of partial AIS were raised as male. The importance of karyotyping girls with inguinal hernias is confirmed, and further attention should be given to genetic counselling for families of complete AIS patients. A large number of cases were misreported as partial AIS, emphasising the importance of undertaking a comprehensive diagnostic evaluation in intersex states. A large percentage of children with partial AIS were raised as boys despite severe genital undermasculinisation, indicating the current lack of validated measures that predict genital response to androgen treatment. The management of AIS is discussed and diagnostic guidelines provided to improve the diagnostic yield in AIS.


Effect of 12 weeks of aquatic strength training on individuals with multiple sclerosis.
Programas de exercícios físicos são recomendados para pacientes com esclerose múltipla. No entanto, são limitados os estudos que envolvem o treinamento aquático de força para a melhoria das capacidades funcionais. Investigar o efeito de um programa de treinamento aquático de força nas capacidades funcionais e nos níveis de força e fadiga de pessoas diagnosticadas com esclerose múltipla. Foram selecionados 29 voluntários com esclerose múltipla. Todos os participantes realizaram uma bateria de testes, incluindo os de capacidades funcionais, nível de força e níveis de fadiga em dois momentos distintos: pré-intervenção e pós-intervenção. O programa de treinamento de força foi realizado durante 12 semanas. Foram utilizados exercícios de força localizados, com controle específico de carga de trabalho, que variou entre 50 e 90% do máximo, de acordo com a semana de treinamento. Para a análise estatística, optou-se por utilizar o teste t de Student na comparação ente os momentos pré- e pós-intervenção. Os resultados demonstraram melhora significativa em todas as variáveis investigadas: teste de 6 min de caminhada (p=0,00); força mão dominante (p=0,02); força mão não dominante (p=0,00); levantar (p=0,00); sentar e levantar-se (p=0,00); subir 15 degraus (p=0,00); descer 15 degraus (p=0,00); calçar meias (p=0,00); gravidade da fadiga (p=0,01); impacto da fadiga (p=0,01). O treinamento aquático de força foi eficiente para melhorar as capacidades funcionais relacionadas à qualidade de vida de pacientes com esclerose múltipla.


The induction of RANKL molecule clustering could stimulate early osteoblast differentiation.
We recently found that the membrane-bound receptor activator of NF-κB ligand (RANKL) on osteoblasts works as a receptor to stimulate osteoblast differentiation, however, the reason why the RANKL-binding molecules stimulate osteoblast differentiation has not been well clarified. Since the induction of cell-surface receptor clustering is known to lead to cell activation, we hypothesized that the induction of membrane-RANKL clustering on osteoblasts might stimulate osteoblast differentiation. Immunoblotting showed that the amount of RANKL on the membrane was increased by the RANKL-binding peptide OP3-4, but not by osteoprotegerin (OPG), the other RANKL-binding molecule, in Gfp-Rankl-transfected ST2 cells. Observation under a high-speed atomic force microscope (HS-AFM) revealed that RANKL molecules have the ability to form clusters. The induction of membrane-RANKL-OPG-Fc complex clustering by the addition of IgM in Gfp-Rankl-transfected ST2 cells could enhance the expression of early markers of osteoblast differentiation to the same extent as OP3-4, while OPG-Fc alone could not. These results suggest that the clustering-formation of membrane-RANKL on osteoblasts could stimulate early osteoblast differentiation.


Osteoma of the ethmoid sinus in a pediatric patient - a case report.
Osteomas of the paranasal sinuses occur rarely in the pediatric population, we find only a few reference of symptomatic osteomas in the literature. Opinions on the indication for surgical treatment are controversial. The authors present a case of symptomatic osteoma of the right ethoimoidal sinus in a 12-year-old boy, who was treated surgically, with endoscopic endonasal approach. The symptomatology, diagnosis and therapy of these tumors in the pediatric patient are discussed. Osteomas of the paranasal sinuses are slow-growing benign lesions. Symptomatic osteomas can grow expansively and cause serious complications. The treatment of osteoma is surgical and the endoscopic approach offers the possibility of removal with cosmetic benefits.


Increasing physical activity in postpartum multiethnic women in Hawaii: results from a pilot study.
Mothers of an infant are much less likely to exercise regularly compared to other women. This study tested the efficacy of a brief tailored intervention to increase physical activity (PA) in women 3-12 months after childbirth. The study used a pretest-posttest design. Sedentary women (n = 20) were recruited from a parenting organization. Half the participants were ethnic minorities, mean age was 33 +/- 3.8, infants' mean age was 6.9 +/- 2.4 months, 50% were primiparas, and mean body mass index was 23.6 +/- 4.2. The two-month intervention included telephone counseling, pedometers, referral to community PA resources, social support, email advice on PA/pedometer goals, and newsletters.The primary outcome of the study was minutes per week of moderate and vigorous leisure-time physical activity measured by the Godin physical activity instrument. All women (100%) returned for post-test measures; thus, paired t-tests were used for pre-post increase in minutes of moderate and vigorous leisure-time physical activity and comparisons of moderate and vigorous leisure-time physical activity increases among ethnic groups. At baseline participants' reported a mean of 3 +/- 13.4 minutes per week moderate and vigorous leisure-time physical activity. At post-test this significantly increased to 85.5 +/- 76.4 minutes per week of moderate and vigorous leisure-time physical activity (p < .001, Cohen's d = 2.2; effect size r = 0.7). There were no differences in pre to post increases in minutes of moderate and vigorous leisure-time physical activity among races. A telephone/email intervention tailored to meet the needs of postpartum women was effective in increasing physical activity levels. However, randomized trials comparing tailored telephone and email interventions to standard care and including long-term follow-up to determine maintenance of physical activity are warranted.


Contamination of sulfonamide antibiotics and sulfamethazine-resistant bacteria in the downstream and estuarine areas of Jiulong River in Southeast China.
Surface water samples from downstream and estuarine areas of Jiulong River were collected in August 2011 and May 2012 for detecting sulfonamide antibiotic residues and isolating sulfamethazine-resistant bacteria. Sulfamethazine was detected in all samples in May 2012 at an average concentration of 78.3 ng L(-1), which was the highest among the nine sulfonamide antibiotics determined. Sulfamethazine-resistant bacteria (SRB) were screened using antibiotic-containing agar plates. The SRB average abundance in the samples was 3.69 × 10(4) and 2.17 × 10(3) CFUs mL(-1) in August 2011 and May 2012, respectively, and was positively correlated to sulfamethazine concentration in May 2012. The 16S rRNA gene sequencing of all the 121 SRB isolates revealed high diversity. Furthermore, the SRB isolates exhibited multidrug resistance, with 48.7% showing resistance to at least three antibiotics. The abundance and persistence of highly diverse SRB and their multidrug resistance are likely to demonstrate the transferable pressure from coastal environments on public health.


Emporiatrics: the study of diseases in travelers.
Travel to developing countries is exhilarating and, for the most part, safe. However, the unwary traveler may encounter unexpected tropical diseases, many of which are preventable. Additionally, infected travelers may return with exotic diseases that pose special problems for ICPs.


[A few remarks regarding 421 cases of trigeminal neuralgia].
Referring to the treatment of 421 patients with trigeminal neuralgia, the authors indicate an early alcoholization or exheyresis in case of therapeutical failure of systemic conservative treatment. Such a management prevents transformation of the peripheral into central neuralgia. Emphasis is on more frequent treatment of neuralgia by dental surgeons.


[The decentralized documentation system '90' of the Study Group for Osteosynthesis Problems (AO)].
The new decentralized documentation system '90' of the "Arbeitsgemeinschaft für Osteosynthesefragen" (Association for the Study of Internal Fixation to ASIF) will be introduced. This system is used for gathering clinical data of operatively treated fractures and their clinical outcome.


A noisy label and negative sample robust loss function for DNN-based distant supervised relation extraction.
As a major method for relation extraction, distantly supervised relation extraction (DSRE) suffered from the noisy label problem and class imbalance problem (these two problems are also common for many other NLP tasks, e.g., text classification). However, there seems no existing research in DSRE or other NLP tasks that can simultaneously solve both problems, which is a significant insufficiency in related researches. In this paper, we propose a loss function which is robust to noisy label and efficient for the imbalanced class dataset. More specific, first we quantify the negative impacts of the noisy label and class imbalance problems. And then we construct a loss function that can minimize these negative impacts through a linear programming method. As far as we know, this seems to be the first attempt to address the noisy label problem and class imbalance problem simultaneously. We evaluated the constructed loss function on the distantly labeled dataset, our artificially noised dataset, human-annotated dataset of Docred, as well as the artificially noised dataset of CoNLL 2003. Experimental results indicate that a DNN model adopting the constructed loss function can outperform other models that adopt the state-of-the-art noisy label robust or negative sample robust loss functions.


Phosphodiesterase type 4 that regulates cAMP level in cortical neurons shows high sensitivity to rolipram.
To characterize the role of phosphodiesterase type 4 (a cAMP-specific and rolipram-sensitive phosphodiesterase) among phosphodiesterases in the regulation of the intracellular cAMP level in cortical neurons, we investigated the effects of phosphodiesterase inhibitors on the intracellular cAMP levels in primary cultured rat cortical neurons. Selective inhibitors of phosphodiesterase type 4 and type 2 significantly enhanced beta-adrenoceptor-mediated cAMP increase. Selective inhibitors of phosphodiesterase type 1, type 3 and type 5/6 had no effect on the cAMP level. Rolipram enhanced the beta-adrenoceptor-mediated cAMP increase in cortical neurons, astrocytes and vascular smooth muscle cells at different minimum effective concentrations (10, 100 and 1000 nM, respectively). These findings indicate that phosphodiesterase type 4, showing a high-sensitivity to rolipram, plays a major role in regulating cAMP in the cortical neurons, and that rolipram at low doses enhances the intracellular cAMP increase in the cortical neurons selectively.


Posterior superficial temporal artery island flap for intra-oral reconstruction: a case report.
A case is presented in which a scalp island flap in an elderly bald male was used for intraoral reconstruction following tumour excision. The flap was based on the posterior branch of the superficial temporal vessels as its arteriovenous system. This flap when available has advantages over other flaps described for intra-oral reconstruction.


Lower antidepressant response to fluoxetine is associated with anxiety-like behavior, hippocampal oxidative imbalance, and increase on peripheral IL-17 and IFN-γ levels.
Major depression is a leading contributor to the global burden of disease. This is mainly related to the disorder chronic and recurrent nature, and to high rates of refractoriness to treatment. Limited efficacy with currently available antidepressants highlights the need for more effective options for treating drug-resistant patients and emphasizes the importance of developing specific preclinical models for treatment-resistant populations. Treatment-resistant depression (TRD) is commonly defined as failure to respond to two or more trials of antidepressants. In this study, we investigated the effect of fluoxetine treatment for fourteen days on the depressive-like behavior and the oxidative and inflammatory parameters of mice submitted to chronic corticosterone administration. After 21 days of subcutaneous corticosterone administration (20 mg/kg/day) and 14 days of oral fluoxetine treatment (10 mg/kg/day, started on day 7 of induction protocol), we separated animals into two groups according to the tail suspension test (TST) results: antidepressant responders (good response to antidepressant, GRA) and non-responders (resistance to antidepressant, AR). Forced swimming test (FST), elevated plus maze test (EPMT), and open field test (OFT) were performed. We found that animals classified as AR (i.e., those with higher immobility values in the TST) demonstrated anxiety-like behavior in the EPMT, increased H2O2 levels, and decreased catalase activity in the hippocampus, as well as increased serum levels of IL-17 and IFN-γ. Our findings suggest that a redox imbalance in the hippocampus, combined with increased levels of peripheral IL-17 and INF-γ, may be involved with an impaired response to fluoxetine.


Metagenomic insights into the spatiotemporal responses of antibiotic resistance genes and microbial communities in aquaculture sediments.
The dissemination of antibiotic resistance genes (ARGs) in aquaculture systems is a potential threat to environmental safety and human health. However, the spatiotemporal distribution pattern of ARGs and key factors associated with their dissemination in aquaculture sediments remain unclear. In this study, ARGs, mobile genetic elements, microbial community composition, heavy metal contents, and nutrient contents of samples collected from a whole culture cycle of fish in a representative aquaculture farm were characterized. The distribution patterns of nine subtypes of ARGs (tetW, tetM, tetA, ermC, ermB, sul1, sul2, floR, and qnrS) showed clear spatiotemporal differences. The absolute abundance of ARGs in aquaculture sediments was higher in winter and in rivers of the aquaculture farm. Proteobacteria was the dominant phylum in all sediment samples. The results of network and redundancy analyses confirmed that the Dechloromonas, Candidatus Accumulibacter, Smithella, Geobacter, and Anaeromyxobacter belonging to Proteobacteria were positively correlated with ARGs, suggesting that these microbial species are potential hosts of corresponding ARGs. Our study highlights that the microbial community is the determining factor for ARG dissemination. Strategies for inhibiting these potential hosts of ARGs should be developed based on controllable factors.


[Assessing Electronic Prescription: A Cross-sectional Study of Pharmacists in Germany].
The GERDA ("Protected e-prescription service for pharmacies") project of the Chamber of Pharmacists (LAK) and Pharmacists Association (LAV) of the federal state of Baden-Wuerttemberg provided the opportunity to prescribe medications within the telemedical portal "docdirekt" that is operated by the Association of Statutory Health Insurance Physicians of Baden-Wuerttemberg. Against this background, the aim of the study was to explore and prioritize barriers and enablers among pharmacists to participate in a medical supply system that includes electronic prescriptions (e-prescriptions). Based on these determinants, recommendations for optimizing the successful implementation of similar care offers were derived. A mixed methods design was chosen to explore and prioritize the determinants. In the first step, determinants for participation in an electronic prescribing system were explored by means of individual interviews of docdirekt tele-physicians, primary care physicians and pharmacists. In a second step, these determinants were prioritized through a quantitative survey of pharmacists. Out of the 523 pharmacists that answered the questionnaire, more than half were willing to participate in an e-prescription system, while 8.5% excluded future participation. A total of 18 determinants for the e-prescription system participation could be explored. The protection of the free pharmacy choice for the patients was identified as the most important determinant, followed by the option of a correction function for e-prescriptions (e. g. to avoid retaxing or medication errors), the integration of the e-prescription into the existing pharmacy IT system and the statutory exclusion of direct contracts with online pharmacies. Time savings and possibly higher remunerations were rated as less relevant. More than half of the pharmacies surveyed stated that they wanted to participate in an e-prescription system. Widespread introduction of e-prescriptions in planned for January 2022. Successful implementation of this move will be facilitated if the identified determinants are taken into consideration by politics, software developers and associations.


Combination of pre-emptive port-site and intraoperative intraperitoneal ropivacaine for reduction of postoperative pain: a prospective cohort study.
To evaluate the effectiveness of intraoperatively applied local ropivacaine added to standard analgesic therapy in reducing postoperative pain intensity and opioid requirement under routine hospital conditions. In this prospective controlled cohort study, 303 consecutive patients receiving a gynaecological laparoscopic intervention at the Jena University Hospital were included. The study cohort (n=168) received, in addition to standard pain management, a port-site (PS) infiltration with ropivacaine prior to incision and intraperitoneal (IP) instillation at the end of surgery. On the first postoperative day patients answered a validated questionnaire, and requirement of rescue analgesics was assessed. Pain intensity was assessed on an 11-point numeric rating scale (NRS) from 0=no pain to 10=most severe pain. Reported pain intensity for movement-related pain was significantly lower (p=.001) in the study group compared with the control group (4.4 (SD 2.4) vs. 5.3 (SD 2.2) respectively). Minimal pain intensity after operation was also significantly lower in the study cohort (2.6 (SD 1.7) vs. 2.1 (SD 1.8), (p=.007)). Significantly fewer patients required rescue opioids for analgesia in the ropivacaine cohort (p=.001). The requested dose of rescue opioid (piritramide) in this cohort was also lower (p=.035) with 6.5mg (SD 4.9) vs. 8.7mg (SD 6.6), and demanded later (p=.001) with 4.3h after surgery vs. 3.1h. Patients in the study cohort experienced less nausea (p=.046). Higher satisfaction scores with pain management were reported in the ropivacaine group 12.7 (SD 2.5) vs. 11.6 (SD 2.8) (p<.001) (16-point NRS with 0=not at all, 15=completely satisfied). Addition of pre-emptive port-site plus intraperitoneal ropivacaine to standard postoperative analgesic therapy reduced postoperative pain intensity and opioid consumption in gynaecological laparoscopy.


In vitro analysis of exfoliated tumor cells in intraluminal lavage samples after colorectal endoscopic submucosal dissection.
Colorectal endoscopic submucosal dissection (ESD) produces exfoliated tumor cells that occasionally cause local recurrence. However, the biological characteristics of these tumor cells have not been clarified. The aim of this study was to clarify the genetic background and viability of exfoliated tumor cells in colorectal ESDs, as well as possible method for their elimination. Post-ESD intraluminal lavage samples from 19 patients who underwent colorectal ESDs were collected. In four patients with adenocarcinoma, gene mutations in the primary tumors and exfoliated cells in lavage samples were analyzed using a next-generation sequencer (NGS). In 15 patients with adenoma or adenocarcinoma, the viability of exfoliated cells and the cell-killing effect of povidone-iodine on exfoliated cells were evaluated. The analysis using a NGS demonstrated that tumors targeted for ESD had already acquired mutations in many genes involved in cell proliferation, angiogenesis, and invasions. Furthermore, gene mutations between the exfoliated tumor cells and tumors resected by ESDs showed a 92 to 100% concordance. The median viable cell counts and the median viability of exfoliated cells in intraluminal lavage samples after ESDs were 4.9 × 105 cells/mL and 24%, respectively. The viability of the exfoliated cells did not decrease even 12 h after ESD. However, contact with 2.0% povidone-iodine solution reduced both viable cell counts and viability, significantly. A large number of tumor cells exfoliated during colorectal ESDs had acquired survival-favorable gene mutations and could survive for some time. Therefore, a lavage using a solution of 2.0% povidone-iodine may be effective against such cells. The prospective study registered 1317, and the retrospective study registered 2729. The prospective study approved on June 20, 2016, and the retrospective study approved on October 6, 2020.


Behavioral characterization in a comprehensive mouse test battery reveals motor and sensory impairments in growth-associated protein-43 null mutant mice.
The growth-associated protein (GAP)-43 is a major neuronal protein associated with axonal growth, neuronal plasticity and learning. The observation that only 5-10% of mice with a full GAP-43 gene deletion survive weaning suggests that basic neural functions are disturbed. Here we used a comprehensive test battery to characterise and quantify the motor and sensory function of surviving adult homozygous GAP-43 (-/-) mice as compared with GAP-43 (+/-) and wild-type animals. The test battery was comprised of motor, sensory, and reflex tests producing 25 measures of locomotion, as well as epicritic, auditory, olfactory and visual function. The analysis revealed significant impairments in muscle strength, limb coordination and balance in GAP-43 (-/-) mice. Furthermore, GAP-43 (-/-) animals were hyperactive and showed reduced anxiety as measured by open field and light dark tests. In sensory tests, GAP-43 (-/-) mice were tested for impaired tactile and labyrinthine function. Abnormal reflexes were found in the contact and vibrissa placing responses, and in the crossed extensor reflex. GAP-43 (+/-) animals showed only moderate abnormalities as compared with wild-type animals. We conclude that GAP-43 is necessary for the development and function of a variety of neuronal systems. The results also show that the comprehensive test battery used in the present study represents a sensitive approach to assess the functional integrity of ascending and descending pathways in genetically manipulated mice.


Artificial urinary sphincter cuffs and safe instrument/catheter passage guidelines.
The artificial urinary sphincter (AUS) is the gold standard for males with urinary incontinence. It is generally a safe procedure with a high degree of satisfaction. However, there is a lifelong risk of infection and erosion. AUS cuffs are commonly placed around the bulbar urethral area. There is always a risk of trauma and erosion of cuffs with catheterization or endoscopy. At this time, there is little guidance as to which size catheters or scopes can pass through each AUS cuff sizes safely. The goal of this study was to determine which size of catheters/scopes can pass through different cuff sizes safely in an ex vivo setting. All AUS cuff sizes available (3.5 cm up to 6.0 cm), catheter sizes between 12 and 22 Fr, and scope sizes 19 Fr flexible/rigid, 21-26 Fr rigid scopes were examined. We used deflated assembled cuffs on the bench (ex vivo) and three different blind observers to measure the free space left between the wall of the cuff and the catheter/scope to be sure that there was consistency. We created a scale from 1 to 3 to determine the ease of passage for each catheter/scope. We also had an MRI radiologist examine bulbar urethra thickness in 20 male patients to determine the average thickness without the bulbospongiosus muscle. Using our average bulbar urethral thickness, we were able to estimate how much free space remained within the urethral lumen and how easy and safe it was to pass each catheter/scope. For 3.5 cm cuffs, 12 Fr catheters pass easily and safely, 14-16 Fr catheters and 19 Fr flexible/rigid scopes can pass through with some mild risk of trauma. Larger catheter/scope sizes cannot pass through without a significant risk of trauma. For 4.0 cm cuffs, 12-14 Fr catheters pass easily and safely. 16-18 Fr catheters and 19-21 Fr rigid/flexible scopes can pass with some mild risk of trauma. Larger catheter/scope sizes cannot pass through safely. For 4.5 cm cuffs, 12-18 Fr catheters and 19 Fr flexible/rigid scopes pass easily and safely. 20-22 Fr catheters and 21 Fr rigid scopes can pass with some mild risk of trauma. Larger catheter/scope sizes cannot pass through safely. For 5.0 cm cuffs, 12-22 Fr catheters and 19-21 Fr flexible/rigid scopes can pass easily and safely. 22-26 Fr scopes can pass with some mild risk of trauma. For 5.5 cm cuffs, all catheters/scopes can pass easily and safely. However, the 26 Fr rigid scope can pass with some mild risk of trauma. For 6 cm cuffs, all catheters/scopes examined can pass easily and safely. Our study can guide urologists in the management of patients with an AUS who need urethral catheters or endoscopy. These recommendations are based on the measurements of our study along with bulbar urethral thickness. In general, greater caution is needed with smaller cuff sizes (3.5-4.5 cm). Our recommendations, with minimal urethral compression, are purposely conservative and safe to avoid trauma and erosion of the AUS cuffs.


Urological operations for solitary kidneys in children.
Depending on the underlying disease, children with solitary kidneys who have to undergo urological operations have the same good or poor prognosis as children with two kidneys (Whiting et al. 1983; Redman and Birsada 1976; Stackl et al. 1983). However, the problem of long-term prognosis persists. It is similar to that for children who have undergone surgery for reflux: a certain number of them will develop renal insufficiency in 20-30 years. Nephrologists estimate that 20% of adults who suffer from renal insufficiency and become dialysis dependent formerly had reflux nephropathy. The influence of reimplantation, performed with good results during the past few years, cannot be assessed so far. Large prospective studies are needed.


Changes of cell surface configuration and regulation of cell proliferation.
The electric surface charge configuration of 3T3 and SV40-3T3 cells was characterized by determining the product of electrophoretic mobility of the cells times the viscosity of suspension medium. This quantity could be shown to change with temperature and/or treatment with calf serum or trypsin in close correlation with the effects of these agents on characteristics of cell proliferation. The present results, taken together with those of earlier studies on cell-electrophoresis and characterization of lipid constituents of the cells, support the hypothesis of a lateral phase separation in the plasmamembrane as triggering process in stimulation of proliferation of resting normal cells.


"Bong lung" in cystic fibrosis: a case report.
Marijuana or "bong" lung has been recently described. Subjects typically develop large peripheral paraseptal lung bullae and are predisposed to spontaneous pneumothoraces. The underlying mechanism for bullae formation is uncertain, but probably relates to direct lung toxicity and repeated barotrauma as the smoker performs frequent valsalva manoeuvres in an attempt to derive a greater drug effect. We describe a case of probable "bong lung" occurring in a 23-year-old Caucasian man with cystic fibrosis who had a history of recurrent pneumothoraces and unusual findings on sputum cytology. Our case highlights the importance of questioning young adult cystic fibrosis patients about illicit drug use and the utility of sputum cytology and computed tomography scanning when patients present with pneumothoraces and deteriorations in clinical status.


[Reverse remodelling of the heart after atrial fibrillation ablation in patients with heart failure with reduced ejection fraction].
To evaluate the effect of atrial fibrillation (AF) catheter ablation (CA) on long-term freedom from AF and left heart reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). There were 47 patients (mean age 53.3 ± 10 years, 39 males) enrolled into single-center observational study, with left ventricular ejection fraction (LVEF) <40 %. Patients underwent CA for AF refractory to antiarrhythmic drugs. Baseline clinical data and diagnostic tests results were obtained during personal visits and / or via secure telemedical services. Personal contact with evaluation of recurrence of AF and echocardiographic values was performed with 30 (64 %) patients. Paroxysmal AF was present in 12 (40 %) patients, persistent - in 18 (60 %). During mean follow-up of 3 years (0.5-6 years) redo ablation was performed in 9 patients (30 %) with average number of 1.3 procedures per patient. At 6 months 24 (80 %) patients were free from AF, at last follow-up - 16 (53 %). The mean time to first recurrence following CA was 15.6±13.3 months. Follow-up echocardiography revealed significant LVEF improvement (р<0,0001), reduction of left atrium size (р<0,0001), left ventricle end-diastolic volume (р<0,002) and left ventricle endsystolic volume (p<0,0001) and mitral regurgitation (р=0,001). AF CA in patients with HFrEF is associated with improvement in systolic function and left heart reverse remodeling. Durable long-term antiarrhythmic effect often requires repeated procedures.


Comparative effect of fucoxanthin and vitamin C on oxidative and functional parameters of human lymphocytes.
The aim of this study was to evaluate the effects of FUCO alone or combined with vitamin C on different features of lymphocyte function related to ROS/RNS (reactive oxygen/nitrogen species) production. For this purpose we have evaluated the cytotoxicity of increasing concentrations of FUCO and vitamin C, the proliferative capacity of stimulated T- and B-lymphocytes, superoxide anion radicals (O(2)), hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) production, antioxidant enzyme activities and the indexes of oxidative damage in proteins (carbonyl and thiol content). We have also evaluated the release of inflammatory cytokines and glucose-6-phosphate dehydrogenase (G6PDH) activity. Healthy human lymphocytes were acutely treated in vitro with FUCO (2 μM) with or without vitamin C (100 μM). Results revealed that human lymphocytes treated with FUCO at 2μM did not present any significant alteration in the proliferation of T- and B-lymphocytes at both resting and stimulated conditions. Moreover, FUCO used at low concentrations showed more pro-oxidant than antioxidant effects, which were recognized by the increased H(2)O(2) and increased NO production. Anti-inflammatory activity of FUCO was confirmed by significantly increased IL-10 and decreased TNF-α production. Vitamin C increased T-lymphocyte proliferation, whereas vitamin C plus FUCO promoted a reduction in the proliferation rate of these cells. All groups decreased pro-inflammatory cytokine TNF-α and increased anti-inflammatory IL-10 production although only vitamin C decreased IFN-γ either alone or when combined with FUCO. Overall, the combination of the antioxidants had more antioxidant and anti-inflammatory effects than when they were applied alone.


Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis.
Fibrin-related markers such as soluble fibrin (SF) and D-dimer are considered useful for the diagnosis of thrombosis. However, the evidence for diagnosis of thrombosis by fibrin-related markers is not well-established. To evaluate the cutoff values of D-dimer and SF in the diagnosis of thrombosis. Plasma concentrations of SF and D-dimer were measured in 784 inpatients suspected of having thrombosis between 1 August 2003 and 31 December 2004, and then correlated with thrombosis. Plasma concentrations of D-dimer and SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, compared with those in patients without thrombosis. When cutoff values of > 3.0 microg mL(-1) for D-dimer and > 6.0 microg mL(-1) for SF were used for the diagnosis, more than 50% of patients (with the exception of liver transplant patients and postoperative patients) had thrombosis. Receiver operating characteristic analysis showed that SF was more useful than D-dimer for the diagnosis of thrombosis (i.e. DVT and DIC). The cutoff value of D-dimer (7.87 microg mL(-1)) was the same for DVT and DIC, while that of SF was slightly lower for DVT (7.05 microg mL(-1)) than for DIC (8.60 microg mL(-1)). Our findings suggest that high levels of plasma fibrin-related markers reflect high risk for thrombosis.


Effects of cooling glove on the human body's recovery after exercise and improvement of exercise ability.
After high-intensity exercises, the body's core temperature increases, affecting the body's metabolism, increasing thermal stress and muscle fatigue. The most popular technique to maximize post-workout recovery is cryotherapy. However, the cooling effect may vary depending on the body part being cooled since body tissues do not process the same perfusion. This study investigates the effects of hand cooling on human body functional recovery and exercise ability improvement by comparing normal rest and rest with hand cooling gloves after high-intensity exercise. Thirty healthy subjects participated in this study wherein they exercised and used normal rest for one session and hand cooling rest for the next. Blood lactate concentration, heart rate recovery rate, VO2 max measurement, and the degree of recovery of muscle strength, muscular endurance, and muscle fatigue were investigated in both groups to determine the efficacy of hand cooling gloves for postexercise recovery. When hands were cooled after exercise, blood lactate concentration and body temperature significantly decreased, and cardiopulmonary function, muscle strength, and muscular endurance significantly recovered. Using hand cooling gloves after exercise could attenuate core temperature elevation and improve postexercise recovery. It could also effectively improve athletic performance without using large-scale facilities.


Stem cell transplantation for chronic myeloid leukaemia: the role of infused marrow cell dose.
Allogeneic stem cell transplantation is a potentially curative option for patients with CML. The optimal donor is an HLA-identical sibling but transplants using unrelated volunteers can also be successful. The factors influencing survival after allogeneic SCT for CML are reasonably well defined. Recently however, the Seattle group have emphasised the influence of a high marrow cell dose on outcome following volunteer unrelated donor SCT for high risk acute leukaemia. We have sought to define factors impacting on transplant related mortality (TRM) in a population of CML patients after allografting with matched sibling or alternative stem cell donors at a single centre over a 20-year period, with emphasis on infused marrow cell dose. Factors entered into a multivariate analysis were: recipient age, recipient CMV serostatus, disease phase, donor sex, cell dose and frequency of CTLP reactivity. In multivariate analysis four factors had an adverse effect on TRM when using a VUD: low marrow cell dose (<3.65 x 10(8) TNC/kg, relative risk 2.05, CI 1.08-3.90, P = 0.029), late disease phase (relative risk 1.68, CI 1.03-2.74, P = 0.038), patient CMV seropositivity (relative risk 1.98, CI 1.25-3.13, P = 0.004) and high frequency of CTLP (relative risk 1.93, CI 1.18-3.13, P = 0.008). For HLA-identical sibling donor transplants the only factor that adversely impacted on TRM was late disease phase (P = 0.0004 in univariate analysis). High infused cell dose is a new modifiable factor associated with reduced TRM following allogeneic SCT using an unrelated donor for the treatment of CML. The data support the recommendation that bone marrow harvest teams should aim to collect the highest possible number of nucleated cells for recipients of unrelated donor transplants.


High mean platelet volume to platelet count ratio as a predictor on poor outcomes after CABG.
To determine the effect of mean platelet volume (MPV) to platelet count (PC) ratio on postoperative poor outcomes, early mortality and long-term survival rate in patients undergoing CABG. Between February 2016 and September 2018, all patients undergoing CABG in our department were retrospectively reviewed. A total of 213 consecutive patients were included in the study. Mean age was 61.5 ± 9.7 years and mean follow-up of all patients was 1.4 ± 0.5 years. All patients were divided into two groups as high and low MPV/PC ratio in terms of 3.825 of cut-off point. 72 patients had a high MPV/PC ratio, whereas, 141 patients had low MPV/PC ratio. The rates of reoperation for early vein-graft occlusion, low cardiac output syndrome and respiratory complication were significantly higher in group 1 (p = 0.03, 0.04 and 0.01). The mean hospital length of stay was higher in group 1 (p = 0.03). MPV/PC ratio for reoperation for early vein-graft occlusion; MPV and ejection fraction for low cardiac output syndrome; hyperlipidemia, chronic renal failure history and MPV/PC ratio for sepsis; male gender, CRF history and CPB time for atrial fibrillation; age, congestive heart failure history, myocardial infarction history and CPB time for the early mortality were found to be independent predictors. Peripheral arterial diseases, USAP and MPV/PC ratio were found to be independent predictors for the late mortality. A high MPV/PC ratio is associated with early vein-graft occlusion and poor postoperative outcomes in the early period after CABG. Furthermore, it has a negative effect on late survival.


Are these liquids explosive? Forensic analysis of confiscated indoor fireworks.
Complete forensic analysis of several confiscated liquids and gels putatively used as firework components was achieved by combining Raman, FTIR spectroscopy, and scanning electron microscopy combined with energy-dispersive spectroscopy (SEM-EDS). The chemical composition of the liquids was consistent with their use as indoor fireworks. Alcohols (methanol and isopropyl alcohol) were used to solubilise compounds producing coloured flames. Boric acid, recently introduced in the list of Substances of Very High Concern (SVHC) for the REACH Regulation of the European Union, was found in one of the samples.


The differentiation of rhythmic structure.
Listeners judged whether two five-tone nonmetric rhythms were the same or different. Each rhythm was presented one, two, or four times to study the process of perceptual differentiation. The results indicated that the listeners perceived these rhythms in terms of the grouping of the tones, and not in terms of the timing between the groups. Two rhythms that had the same perceptual grouping were judged as being identical, even if the timing between the groups was different. The perception of the groupings of tones developed gradually. If each rhythm was presented only once, then the listeners had only a global percept, focused on groups (runs) of three elements, and often judged two different rhythms as being identical. If the rhythms were presented two or four times, then the grouping of the tones became more differentiated and the listeners were less likely to judge different patterns as being identical. Thus, perception of auditory rhythmic structure appears to follow the same developmental process as the perception of visual spatial structure.


Strategies for designing and validating immunostimulatory siRNAs.
Specific clinical applications of RNA interference (RNAi) can benefit from a concurrent activation of the immune system. This is the case for small interfering RNAs (siRNAs) with antitumor or antiviral activities. This chapter provides a brief overview of the strategies reported to date to design siRNAs with gene silencing and immune activating properties, as well as methods for the validation of immunostimulatory activities.


Abnormalities of synaptic mitochondria in autism spectrum disorder and related neurodevelopmental disorders.
Autism spectrum disorder (ASD) is a neurodevelopmental condition primarily characterized by an impairment of social interaction combined with the occurrence of repetitive behaviors. ASD starts in childhood and prevails across the lifespan. The variability of its clinical presentation renders early diagnosis difficult. Mutations in synaptic genes and alterations of mitochondrial functions are considered important underlying pathogenic factors, but it is obvious that we are far from a comprehensive understanding of ASD pathophysiology. At the synapse, mitochondria perform diverse functions, which are clearly not limited to their classical role as energy providers. Here, we review the current knowledge about mitochondria at the synapse and summarize the mitochondrial disturbances found in mouse models of ASD and other ASD-related neurodevelopmental disorders, like DiGeorge syndrome, Rett syndrome, Tuberous sclerosis complex, and Down syndrome.


Determination of Proinflammatory and Antiinflammatory Cytokines by ELISA Technique.
The main objective of this chapter is to determine inflammatory and anti-inflammatory cytokines in patients with or without preeclampsia by means of the enzyme-linked immunosorbent assay (ELISA) technique. In this chapter, 16 cell cultures were obtained from different patients admitted to the hospital with term vaginal delivery or cesarean section. Here, we describe the ability to quantify the presence of cytokines in cell culture supernatants. The supernatants of the cell cultures were collected and concentrated. The concentration of IL-6 and VEGF-R1 was measured by ELISA to determine the prevalence of alterations in the samples studied. We observed that the sensitivity of the kit allowed the detection of several cytokines in a range between 2 and 200 pg/mL. The test was performed using the ELISpot method (5×), which allowed a higher level of precision.


Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development.
Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice disrupts gut homeostasis, characterized by increased proportions of colonic CX3CR1hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3CR1hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis.


Predicting intentions to get the COVID-19 vaccine in India: An integration of theory of planned behaviour and health belief model.
The aim of the study was to determine intention to receive Coronavirus disease-19 (COVID-19) vaccination in India. An integrated model of Theory of Planned behaviour (TPB) and Health Belief Model (HBM) was used. Online survey was conducted in Delhi NCR region to find out the intention to receive vaccination. Data was collected from 845 respondents during 15 February 2021-15 March 2021, just after COVID-19 vaccination became available in the India. Partial Least Square-Structural Equation Modelling was used to establish the relationships. The results of the analysis show that proposed framework is significant and explained 71% variance in intentions. Attitude, subjective norm, perceived behaviour control and self-efficacy from the TPB had direct (or significant independent) effects on intention and perceived benefits, perceived susceptibility from the HBM have indirect effect on the intentions through attitude. The present study can be used to maximise the uptake of vaccination in any future pandemic. This theoretically-driven model can be used to guide health policy makers and health care providers to increase the uptake of vaccination.


A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop.
Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer cell growth and survival and has been implicated in cancer pathophysiology and treatment. Here we report a novel function for IGF-1R in p53-dependent apoptotic response. We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein. Notably, IGF-1R inhibition increases p53 protein stability by reducing p53 ubiquitination and maintains p53 at low levels by decreasing p53 synthesis, thus rendering p53 insensitive to stabilization after DNA damage. The accumulation and apoptosis of DNA-damage-induced p53 is therefore reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5' untranslated region of p53 and mdm2 messenger RNA. The eukaryotic translation initiation factor 4F complex is also involved in this translational inhibition. These results demonstrate an unexpected role for translational control by IGF-1R in p53-mediated apoptosis.


Cutaneous vasculitis as a presenting manifestation of acute myeloid leukemia.
One of the rare causes of secondary vasculitides is malignancy. Hematological malignancies produce secondary vasculitis more frequently than solid malignancies. Here in we report a case of acute myeloid leukemia presenting with anti-neutrophil cytoplasmic antibody-positive vasculitis. This case highlights the importance of looking for underlying malignancies, especially leukemias in patients presenting with features of systemic vasculitides.


Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson's disease in patients with freezing of gait.
Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson's disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.


SEM characterization and ageing analysis on two generation of invisible aligners.
The purpose of the in vitro study is to investigate and compare the morphological features and the chemical stability in weight of two different polyurethane-based blends, Smart Track (LD30) and Exceed30 (EX30), used for orthodontic aligners manufacture before and after the oral usage. Twenty orthodontic aligners were randomly selected: 10 LD30 and 10 EX30, each group was divided in two subgroups, never used and intra-orally aged. By the employment of a Stereomicroscope, a section of 5 × 5 mm was cut from the buccal surface of the incisal region of each aligner. All samples were subjected to Scanning Electron Microscopy and Ageing tests in different solutions to simulate the hostility of the oral environment. The statistical method used was t-test. At SEM images, LD30 appears more homogeneous in texture respect to EX30. However, after clinical usage, both materials show significant structural alterations: findings have been supported by higher magnifications at SEM, by which it is clearly to observe many superficial cracks cross through the polymer structures of LD30U, absent in never used samples. LD30U surface becomes also smoother due to the disappearance of most of the conglomerates, but at the same time also rougher while EX30U shows a greater irregularity and porosity in which large and deep cracks are also highlighted. Although these changes occur persistently, in the aging tests no significant weight loss from both materials has been found, confirming the initial hypothesis of a good chemical stability and safety of both polyurethane mixtures even in conditions of severe hostility. LD30 is the expression of the technological evolution of EX30, this is made evident above all by its morphological architecture, more homogeneous and defined but also by the chemical stability that can be appreciated even in evident critic situations.


Chloride dependence of frusemide- and phloretin-sensitive passive sodium and potassium fluxes in human red cells.
1. In outdated human red blood cells, there was a Ko-dependent, ouabain-insensitive efflux of Na that was inhibited by frusemide and phloretin. 2. It was reduced or absent (a) in media containing Ca or Mg, (b) in fresh cells. 3. In media with Cl partly replaced by NO3, Na efflux, and its sensitivity to Ko and frusemide, were reduced. 4. The saturable component of ouabain-insensitive K influx was dependent on Cl and inhibited by frusemide and by phloretin. 5. Bromide also supported a frusemide-sensitive, ouabain-insensitive K influx but acetate and SO4 (like NO3) did not.


The approach to ovarian dermoids in adolescents and young women.
Mature cystic teratomas (MCTs) are the most common ovarian neoplastic lesions found in adolescents. MCTs are usually asymptomatic and are often discovered incidentally on exam or imaging. The recurrence rate of MCTs following cystectomy is 3-4% and incidence of malignant transformation is estimated to be 0.17-2%. Given the accuracy with which MCTs can be diagnosed preoperatively studies suggest that these lesions can be treated surgically using laparoscopic techniques. The management of MCTs in the adolescent population poses unique challenges given the potential impact on sexual development and fertility. A 17-year-old female was found to have bilateral adnexal masses consistent in appearance with MCTs on computed tomography after a motor vehicle accident. She underwent exploratory laparotomy with pathology confirming the presence of bilateral ovarian MCTs. Three years later she returned to the office with occasional abdominopelvic pain. Ultrasound revealed bilateral complex cysts suggestive of recurrent MCTs. She was expectantly managed with serial ultrasounds and after 24 months, slow but visible growth of the MCTs was confirmed. The patient is now 22 years old and asymptomatic. What is the most appropriate management? The risks of expectant management in women like the one presented are small. This suggests that although the traditional treatment for MCTs is laparoscopic ovarian cystectomy, in children and adolescents with MCTs we should consider close follow-up without intervention to preserve ovarian function and future fertility.


Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.
This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients. PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot. Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate. Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.


Separate intracellular pathways for insulin receptor recycling and insulin degradation in isolated rat adipocytes.
To gain insight into the sequence of events that follow endocytotic uptake of insulin receptor complexes, we have examined the interrelationship between the degradative pathway of the insulin ligand and the recycling pathway of the insulin receptor. Tris(hydroxymethyl)aminomethane and other nonamphoteric amines were found to selectively impair insulin receptor recycling while leaving the insulin-degradative pathway intact. In contrast, low concentrations of the lysosomotropic agent chloroquine markedly inhibited intracellular insulin degradation but had little or no affect on the recycling of internalized receptors. Thus, we conclude: (1) that insulin dissociates from its receptor after endocytotic uptake and both receptor and ligand follow a separate intracellular pathway; and (2) that receptor recycling and insulin degradation can be selectively inhibited by Tris and chloroquine, respectively, highlighting the potential usefulness of these agents as intracellular probes in the study of receptor-ligand metabolism.


MRI documentation of hemorrhage into post-traumatic subdural hygroma.
Rapid enlargement of a post-traumatic hygroma was demonstrated by MRI in a patient who had sequential studies performed after head injury. The enlargement was shown to be due to hemorrhage into the hygroma.