[USE OF QuantiFERON® TB-GOLD IN-TUBE IN A CONTACT INVESTIGATION TO DETERMINE THE ONSET OF TUBERCULOSIS WITH OR WITHOUT LATENT TUBERCULOSIS INFECTION TREATMENT].
QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis. Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases. (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001). Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G-positive contacts.


What do Demand-Control and Effort-Reward work stress questionnaires really measure? A discriminant content validity study of relevance and representativeness of measures.
The Demand-Control (DC) and Effort-Reward Imbalance (ERI) models predict health in a work context. Self-report measures of the four key constructs (demand, control, effort, and reward) have been developed and it is important that these measures have good content validity uncontaminated by content from other constructs. We assessed relevance (whether items reflect the constructs) and representativeness (whether all aspects of the construct are assessed, and all items contribute to that assessment) across the instruments and items. Two studies examined fourteen demand/control items from the Job Content Questionnaire and seventeen effort/reward items from the Effort-Reward Imbalance measure using discriminant content validation and a third study developed new methods to assess instrument representativeness. Both methods use judges' ratings and construct definitions to get transparent quantitative estimates of construct validity. Study 1 used dictionary definitions while studies 2 and 3 used published phrases to define constructs. Overall, 3/5 demand items, 4/9 control items, 1/6 effort items, and 7/11 reward items were uniquely classified to the appropriate theoretical construct and were therefore 'pure' items with discriminant content validity (DCV). All pure items measured a defining phrase. However, both the DC and ERI assessment instruments failed to assess all defining aspects. Finding good discriminant content validity for demand and reward measures means these measures are usable and our quantitative results can guide item selection. By contrast, effort and control measures had limitations (in relevance and representativeness) presenting a challenge to the implementation of the theories. Statement of contribution What is already known on this subject? While the reliability and construct validity of Demand-Control and Effort-Reward-Imbalance (DC and ERI) work stress measures are routinely reported, there has not been adequate investigation of their content validity. This paper investigates their content validity in terms of both relevance and representativeness and provides a model for the investigation of content validity of measures in health psychology more generally. What does this study add? A new application of an existing method, discriminant content validity, and a new method of assessing instrument representativeness. 'Pure' DC and ERI items are identified, as are constructs that are not fully represented by their assessment instruments. The findings are important for studies attempting to distinguish between the main DC and ERI work stress constructs. The quantitative results can be used to guide item selection for future studies.


The role of telemedicine for symptoms management in oral medicine: a retrospective observational study.
Severe acute respiratory syndrome coronavirus 2 has had devastating effect on access to care in many specialties and dental services including oral medicine. Following the shelter-in-place orders in March 2020, we implemented Tele(oral)medicine practices for the diagnosis and management of some oral medicine conditions. To assess the role of telemedicine visits with respect to managing pain among patients affected by oral diseases. A retrospective chart review for all the new patients seen at their first visit via telemedicine between April 2020 and December 2020. The patient-reported pain score was recorded at each visit using a 0-10 scale. Differences in oral pain from the first fist to the follow-up visit of the patients were evaluated using the Wilcoxon signed-rank test. A total of 137 new patients were included with a median age of 56 years. If seen in person, patients would have travelled a median distance of 65 miles. The most common oral conditions seen were reactive/inflammatory lesions. There was a 3-point median pain reduction from the first video visit to the first follow-up (p < 0.05) and a self-reported 65% median improvement of oral symptoms. Tele(oral)medicine was an effective method for symptoms management of oral medicine conditions.


Comparison of ozone and chlorine in low concentrations as sanitizing agents of chicken carcasses in the water immersion chiller.
The aim of this study was to investigate the effects of the use of chlorine or ozone as sanitizing agents in the water of chicken immersion chilling, using the residual levels usually applied in Brazil (1.5 ppm), comparing the effects of these treatments on the microbiological, physicochemical, and sensory characteristics of carcasses. Chicken carcasses were chilled in water (4°C) with similar residual levels of ozone and chlorine until reaching temperatures below 7°C (around 45 min). The stability of carcasses was assessed during 15 days of storage at 2 ± 1°C. Microbiological, surface color (L*, a*, b* parameters), pH value, lipid oxidation (thiobarbituric acid reactive substances index), and sensory evaluation (on a 9-point hedonic scale for odor and appearance) analyses were carried out. The presence of Salmonella was not detected, coagulase-positive staphylococci counts were below 10(2) CFU/ml of rinse fluid, and Escherichia coli and total coliform counts were below 10(5) CFU/ml of rinse fluid until the end of the storage period for both treatments. Psychrotrophic microorganism counts did not differ (P > 0.05) between chlorine and ozone treatments, and both values were near 10(9) CFU/ml of rinse fluid after 15 days at 4 ± 1°C. pH values did not differ between treatments (P > 0.05) or during the storage period (P > 0.05). In addition, neither chlorine nor ozone treatment showed differences (P > 0.05) in the lipid oxidation of carcasses; however, the thiobarbituric acid reactive substances index of both treatments increased (P ≤ 0.05) during the storage period, reaching values of approximately 0.68 mg of malonaldehyde per kg. Samples from both treatments did not differ (P > 0.05) in their acceptance scores for odor and overall appearance, but in the evaluation of color, ozone showed an acceptance score significantly higher (P ≤ 0.05) than that for the chlorine treatment. In general, under the conditions tested, ozone showed results similar to the results for chlorine in the disinfection of chicken carcasses in the immersion chilling, which may indicate its use as a substitute for chlorine in poultry slaughterhouses.


DHRS7 is an immune-related prognostic biomarker of KIRC and pan-cancer.
Renal clear cell carcinoma (KIRC) is one malignancy whose development and prognosis have been associated with aberrant DHRS7 expression. However, the catalytic activity and pathophysiology of KIRC are poorly understood, and no sensitive tumor biomarkers have yet been discovered. In our study, we examined the significant influence of DHRS7 on the tumor microenvironment (TME) and tumor progression using an overall predictable and prognostic evaluation approach. We found novel cancer staging, particularly in KIRC, as well as potential therapeutic drugs out of 27 drug sensitivity tests. Using Perl scripts, it was possible to determine the number of somatic mutations present in 33 tumors, as well as the relative scores of 22 immune cells using CIBERSORT, the relationship between immune infiltration and differential expression using TCGA data, and the immune microenvironment score using the estimate technique. Our results show that DHRS7 is abnormally expressed in pan-cancer patients, which influences their survival. Low DHRS7 expression was associated with late clinical stages and a low survival rate in KIRC patients, suggesting a poor prognosis and course of treatment, in HNSG, MESO, and KIRC patients. We also found that DHRS7 was associated with TMB and MSI in certain tumors. Using KIRC as an example, we discovered a negative correlation between DHRS7 expression and immunological assessments, suggesting that this substance might be used as a tumor biomarker.


[Biomechanical study of vertebroplasty with geneX(®) cement augmentation in a calf osteoporotic vertebral compression fracture model].
To evaluate the biomechanical properties of geneX cements for use in vertebroplasty in a calf osteoporotic vertebral compression fracture model. Thirty vertebral bodies (T(9)-L(4)) were harvested from 4 fresh calf spines. The bone mineral density was measured with dual-energy radiographic absorption. Osteoporotic vertebral model was induced in each vertebra using decalcifying chemical agents, and was then compressed to determine their initial strength and stiffness before injecting the cement. Thirty vertebral bodies were divided randomly into geneX(®) cement group, CSC group, and PMMA group. The fractures were repaired using a transpedicular injection of cements and re-compressed to measure posttreatment strength and stiffness. The normal mean BMD of the calf vertebra was 1.425∓0.072 g/cm(2), which was reduced significantly to 1.074∓0.065 g/cm(2) after decalcification. The mean injected volume was similar between geneX(®) (4.5∓0.7 ml), CSC (4.3∓0.8 ml) and PMMA (3.8∓0.4 ml) groups. The vertebral strength was restored after the treatment to 1198∓529 N in geneX(®) group, 1212∓430 N in CSC group and 1672∓704 N in PMMA group. All the cements produced significantly greater strength than the initial strength (P<0.05). The augmented strength in geneX(®) and CSC groups were similar (P>0.05), but both were significantly less than that in PMMA group (P<0.05). The stiffness in geneX(®), CSC, and PMMA groups was 233∓130, 242∓191, and 323∓145 N/mm, respectively, showing no significant difference between them (P>0.05). No significant difference was found in the augmented stiffness among the 3 cements (P>0.05). geneX(®) cement is a useful alternative to PMMA in vertebroplasty for osteoporotic vertebral compression fractures, but further study is needed to evaluate its biosorption in vivo.


Bilateral internal thoracic artery grafting is associated with significantly improved long-term survival, even among diabetic patients.
This study examines if bilateral internal thoracic artery (BITA) grafting provides improved outcomes compared with single internal thoracic artery (SITA) grafting, in the modern era, in which diabetes mellitus and obesity are more prevalent. The Society of Thoracic Surgeons database at a single large academic center was reviewed for all consecutive isolated coronary artery bypass grafting patients with two or more distal anastomoses from January 1, 2002, through December 31, 2010. Propensity-adjusted logistic and Cox regression models were used to estimate the effect of BITA on short-term outcomes and long-term survival for diabetic and nondiabetic patients. A total of 3,527 coronary artery bypass grafting operations (812 BITA, 2,715 SITA) were performed. Fewer BITA than SITA patients had diabetes (28.6% vs 44.7% p<0.001). There was no significant difference in 30-day rates of death, stroke, or myocardial infarction between nondiabetic patients who had BITA vs SITA, or between diabetic patients who had BITA vs SITA. BITA grafting conferred a 35% reduction (95% confidence interval, 12% to 52%, p=0.006) in the long-term hazard of death equally for nondiabetic and diabetic patients (p=0.93). Deep sternal wound infection was more common among diabetic than among nondiabetic patients (1.5% vs 0.7%), but was similar within nondiabetic (1.0% vs 0.6%) and diabetic patients (1.7% vs 1.5%) who had BITA vs SITA. Overall, BITA and SITA patients had similar rates of deep sternal wound infection (1.2% vs 1.0%). BITA grafting confers a long-term survival advantage and should be performed whenever suitable coronary anatomy exists and patient risk factors allow an acceptable risk of deep sternal wound infection.


[SPA-1: semiology for phenotyping AMD: precursors].
A reliable classification of AMD subgroups is necessary prior to any genetic or clinical investigation. For this purpose, we evaluated a selected list of items for AMD based on color photographs of the fundus but also on fluorescein and ICG angiographies and OCT. The first step (SPA-1) is to evaluate the interobserver agreement for AMD precursors. The 30 items for AMD precursors, choroidal neovascularization and atrophy, were chosen from the literature. We selected 20 eyes from 20 consecutive patients affected by various forms of these precursors from the prospective NAT-2 study. Grading was based on color photographs of fundus, red-free frames, and fluorescein angiography. For each eye, five grids were filled in by four independent, experienced readers from our reading center and one expert. Within-subject variance was studied. Within subject variance showed the greatest agreement between graders for drusenoid pigment epithelial detachment (variance=0.000). The worst value for within subject variance (0.255) was recorded for the item "intermediate drusen between 5 and 20." This evaluation of our first grid for AMD precursors shows high agreement between graders for most of the items. The item with the lowest agreement should be modified according to the comments of the physicians. This grid could be implemented for phenotypic classification of ARM and AMD in future clinical or genetic studies.


[The way for carrying medicine and its containers (IX): "Packaging insert in the Edo Period (1600-1867)"].
In the Edo Period a packaging insert for a patent medicine had two characters; the one was instructive and the other was advertising for taking a medicine. As there was not enough space in packaging for a patent medicine at thet time to describe the instruction for the medicine, history of the medicine, indication, how to take it, etc., they were shown on the back of the wrapping paper. Though some packaging inserts described volubly the merit of their medicines, most of them did not. It was influenced by a writer of the packaging insert.


Nondisclosure during psychotherapy supervision: validation of the German version of the supervisory questionnaire (SQ).
Nondisclosure is considered to be a central obstacle to effective psychotherapy supervision. The aim of the current study was the validation of the German version of the Supervisory Questionnaire (SQ; Yourman & Farber, 1996), a short measure for the assessment of supervisee nondisclosure. The investigation was based on a sample of 589 supervisees. Confirmatory factor analyses suggested a two-factor model of the SQ which included one factor describing nondisclosure regarding the patient (α=.74) and another describing nondisclosure regarding the supervisor (α=.71). The SQ demonstrated satisfactory convergent and discriminant validity. Additionally assessed supervisee characteristics accounted for 16% of the variance in nondisclosure. These results provide general support for the reliability and validity of the SQ in a large sample of supervisees.


[A case of nonsystemic vasculitic neuropathy with anti-neutrophil cytoplasm antibody (ANCA)].
A 26-year-old woman with mononeuropathy multiplex complained of severe pain of right foot and ipsilateral steppage gait. Careful examination failed detect evidence of systemic lesions. Sural nerve biopsy revealed myelin ovoids and loss of myelinated fibers, which were different in severity among the fascicles. There were mild mononuclear cell infiltrations around arterioles in the epineurium. A diagnosis of nonsystemic vasculitic neuropathy (NSN) was made. Anti-neutrophil cytoplasm antibody (ANCA), a specific marker for microscopic polyarteritis nodosa and Wegener's granulomatosis, was positive in the patient. Oral administration of prednisolone ameliorated the sensorimotor disturbances, and ANCA turned to be negative. This is the first report of a patient with NSN showing positive ANCA.


Repeated, within-session resurgence.
Resurgence is a reliable, transient effect that only occasionally is replicated more than once within a single experiment or subject. In the present experiments, within-session resurgence was generated repeatedly by dividing individual sessions into three phases (Training, Alternative-Reinforcement, and Resurgence-Test). In Experiments 1 and 2, resurgence reliably occurred in most of the 22-30 daily sessions when responding was reinforced on, respectively, fixed- and variable-interval schedules. Resurgence magnitude and duration did decrease across replications for some subjects, but not for others. To examine the utility of the procedure in studying the effects of an independent variable on resurgence, in Experiment 3 the effects of rich and lean baseline and alternative reinforcement rates on resurgence were compared. The target response was eliminated more rapidly, resurgence occurred more often, and usually was greater following rich alternative reinforcement rates. Resurgence was of greater magnitude when the baseline reinforcement rate was relatively lean compared to the alternative reinforcement rate. These experiments provide a reliable method for generating resurgence within individual sessions, instead of across multiple-session conditions, that can be repeated over many successive sessions.


Mapping between sound, brain and behaviour: four-level framework for understanding rhythm processing in humans and non-human primates.
Humans perceive and spontaneously move to one or several levels of periodic pulses (a meter, for short) when listening to musical rhythm, even when the sensory input does not provide prominent periodic cues to their temporal location. Here, we review a multi-levelled framework to understanding how external rhythmic inputs are mapped onto internally represented metric pulses. This mapping is studied using an approach to quantify and directly compare representations of metric pulses in signals corresponding to sensory inputs, neural activity and behaviour (typically body movement). Based on this approach, recent empirical evidence can be drawn together into a conceptual framework that unpacks the phenomenon of meter into four levels. Each level highlights specific functional processes that critically enable and shape the mapping from sensory input to internal meter. We discuss the nature, constraints and neural substrates of these processes, starting with fundamental mechanisms investigated in macaque monkeys that enable basic forms of mapping between simple rhythmic stimuli and internally represented metric pulse. We propose that human evolution has gradually built a robust and flexible system upon these fundamental processes, allowing more complex levels of mapping to emerge in musical behaviours. This approach opens promising avenues to understand the many facets of rhythmic behaviours across individuals and species. This article is part of the theme issue 'Synchrony and rhythm interaction: from the brain to behavioural ecology'.


Assisted Relaxation Therapy for Insomnia in Older Adults With Mild Cognitive Impairment: A Pilot Study.
Insomnia symptoms are prevalent in older adults with mild cognitive impairment (MCI) and can pose treatment challenges. We tested the feasibility, acceptability, and preliminary efficacy of assisted relaxation therapy (ART) to improve insomnia symptoms in community-dwelling older adults with MCI. In this pilot RCT, 25 participants were assigned to intervention or control groups for 2 weeks. The final sample (n = 20) consisted of all Black, primarily female (70%) older adults (mean age 69.10; SD = 7.45) with mean Montreal Cognitive Assessment scores of 21.10 (SD = 2.49). Recruitment was timely; attrition was low (80%). Participants were able to use ART (average use 7.00; SD = 5.07 days). Participants in the ART group improved on Insomnia Severity Index (ISI) (- 7.10; 95% CI [-11.63, -2.55]; p = .004) compared to baseline. There were clinically meaningful mean change scores on ISI for the intervention group compared to the control (- 7.10 vs. - 4.33). Results provide justification for testing ART in a fully powered clinical trial.


The age profile of respiratory syncytial virus burden in preschool children of low- and middle-income countries: A semi-parametric, meta-regression approach.
Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies. We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden. We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children.


Why pedal cyclists should wear safety helmets.
The safety of motor vehicle occupants has been improved dramatically by legislation compelling the wearing of seat belts; protection of motor cyclists against head injury has followed the mandatory wearing of a safety helmet. Bicyclists have been relatively ignored, which is especially regrettable when two thirds of bicycle casualties are school children. Helmets are worn by approximately 25 per cent of adult bicyclists using arterial roads but by less than five per cent of school children.


[A study of the drug distribution on intra-hepatic arterial infusion chemotherapy; how much difference between continuous infusion and rapid infusion?].
The subjects were 41 cases with implantable reservoir systems for unresectable hepatic tumors. We evaluated the difference in drug distribution between intra-hepatic arterial continuous infusion and rapid infusion using hepatic perfusion scintigraphy by 99mTc-macroaggregated albumin via reservoirs. The 41 cases were divided into 2 groups (A and B) according to the imaging of the perfusion scintigraphy. There were 17 cases in group A with equal distribution and 24 cases in group B with a different distribution between the continuous infusion and the rapid infusion. The 24 cases in group B were subdivided into groups according to the distribution of 99mTc-MAA in and around liver. In some cases the distribution pattern after rapid infusion improved more than with continuous infusion. These results suggested that the infusion method must be selected for every case.


When ESKD complicates the management of pain.
Pain is one of the most common symptoms reported by patients with end-stage kidney disease (ESKD) and negatively impacts their health-related quality of life (HRQOL), dialysis adherence, healthcare utilization, and mortality. There are a number of patient-related and health system-related barriers that make it very challenging to treat pain in these patients. Moreover, the limited availability of efficacious and safe nonopiate analgesic options has led to over-use of opioids in this population. We propose a framework for pain assessment and tailored treatment using nonpharmacological and pharmacological approaches to optimize pain management and opioid use. Additionally, we recommend system-level changes to improve care coordination and pain management in ESKD patients.


[Effect of acute exposure to high altitude on pharmacokinetics of propranolol and metoprolol in rats].
To study the pharmacokinetics of propranolol and metoprolol in rats after acute exposure to high altitude. Wistar rats were randomly assigned into 4 groups for treatment with intragastric administration of propranolol or metoprolol after acute exposure to high altitude (4010 m) or normal altitude (50 m). Venous blood samples were collected from the rats at different time points after drug administration to determine the drug concentrations in the plasma and plasma ultrafiltrate using liquid chromatography-mass spectrometry (LC-MS/MS). The protein binding rate of propranolol was significantly increased but that of metoprolol remained unchanged after acute exposure to high altitude. Compared with the rats exposed to normal altitude, the rats with acute exposure to high altitude showed significant alterations in the pharmacokinetic parameters of the drugs, shown by increased Cmax and AUC, prolonged t1/2 and MRT, and lowered Clz/F of propranolol, and by increased Tmax and prolonged t1/2 and MRT of metoprolol without obvious changes of the parameters of the compartmental model. Significant changes in the pharmacokinetics of propranolol and metoprolol occur in rats after acute exposure to high altitude possibly in relation to, apart from the changes in plasma protein binding ratio and blood gas, alterations in metabolic enzyme activities, increased blood viscosity, and species and general conditions of the animals.


Vascular Pathology of Ischemia/Reperfusion Injury of Rat Small Intestine.
Ischemia/reperfusion (I/R) injury of the small intestine caused by occlusion of the superior mesenteric artery affects the intestinal tissue as well as components of the blood circulatory system from the microvasculature to mesenteric vessels. The aim of this work was to study the correlation between the dynamics of destruction development in the intestinal tissue, microvasculature, and mesenteric vessels in I/R of the small intestine. The microvasculature was analyzed by whole-organ continuous monitoring of the intestinal mucosal blood perfusion by laser Doppler flowmetry during the entire I/R. Real-time RT-PCR was used to assess gene expression of NF-κB, caspase-3, Ki67, and TNF-α in blood vessels. At the start of reperfusion, the first targets to be disrupted are microvessels in the apical villi. Injury of the apical part of the microcirculatory bloodstream correlates with the reduction in intestinal mucosal blood perfusion, which occurred simultaneously with apical villous destruction. By the end of the reperfusion period, the low intestinal mucosal blood perfusion is mirrored by the destruction of the microvasculature and mucosal structures in the entire organ. The development of mesenteric vessel injury is characterized by a change in NO metabolism and damaged endothelial cells concomitant with an alteration in the expression of genes encoding NF-κB, caspase-3, and Ki67 by the end of the reperfusion period. In I/R injury, detrimental effects on the intestinal tissue, microvasculature, and mesenteric vessels develop and exhibit common mechanisms of function, which show strong correlations.


Actinium-225 conjugates of MAb CC49 and humanized delta CH2CC49.
Radioisotopes with moderate half-lives are essential for conventional radioimmunotherapy using tumor-selective MAbs which require days for localization. Actinium-225, with a half-life of 10 days and a yield of 4 alpha particles in its decay chain, may be an ideal choice for tumor-targeted radioimmunotherapy. Release of daughter radioisotopes from the primary chelator after the first decay has been a complication with the use of 225Ac. It has been reported that the domain-deleted product of MAb CC49, Hu-delta CH2 CC49, is able to extravasate and penetrate more deeply into tumors than the parent IgG molecule. We reasoned that once the 225Ac-chelate-MAb had penetrated into the tumor, the daughter radioisotopes would remain trapped even if they had been released from the primary chelator. Actinium-225 HEHA MAb CC49 conjugates were tested for distribution, micro-distribution and therapy in immunocompromised mice which had LS174T tumors growing at subcutaneous or intramuscular sites. Both 125I and 225Ac CC49 and Hu-delta CH2 CC49 were efficient in delivery of the radioisotopes to tumor sites. Tissue micro-autoradiography for the two antibody forms did not demonstrate any differences in micro-distribution of either 125I or 225Ac in the tumor. Furthermore, there was no detectable difference for the two carriers in the tumor retention of daughter radioisotopes from 225Ac. Therapy experiments with 225Ac were complicated by radiotoxicity of the conjugates. The lethal dose was about 0.5 microCi in two strains of mice regardless of the carrier. At injected doses of 0.5 and 0.25 microCi, CC49 was slightly active in tumor stasis, whereas no consistent significant effect of 225Ac-Hu-delta CH2 CC49 on growth of tumors was observed. The potential of 225Ac in radioimmunotherapy is limited by the radiotoxicity of its daughter radioisotopes. Its potential will only be realized if stable conjugates, capable of daughter radioisotope retention, can be devised.


The management of ectopic breast cancer--case report.
Ectopic breast tissue occurs when the mammary ridge fails to resolve during embryonic development. Ectopic breasts, either supernumerary or aberrant, have an incidence of 6%. Ectopic breast tissue is however hardly mentioned in the literature. Also benign and malignant alterations in these "breasts" are under-reported. The lifetime risk of women being diagnosed with breast cancer is 13%. It should be recommended that these "breasts" be included in the screening. Due to the unawareness this is generally not happening. The present article describes a case of ectopic breast cancer and discusses therapeutic management. A subcutaneous mass along the 'milk line' should be examined carefully and any suspicious lesions should be approached according to the guidelines for the management of symptomatic breast disease. Ipsilateral prophylactic mastectomy has no role in the management of a single ectopic breast cancer tissue.


Effect of dietary selenium on tumor induction by an oncogenic virus.
Mice exposed to selenium-supplemented or -deficient rations were inoculated with an oncogenic virus, Rauscher leukemia virus (RLV), Splenic lesions were not altered by dietary selenium supplementation or depletion. It is concluded that selenium does not affect neoplasia induced by RLV in mice.


Analytic Training for Junior Investigators in Minority Aging Research: The Michigan Model.
Since 1997, the Resource Centers for Minority Aging Research Program at the National Institute on Aging has been the model for training social and behavioral scientists in minority aging and health disparities research. The latest cycle of these Centers implemented a new structure for the analytic training of junior investigators and for advancing methodologic work relevant to improving the rigor of minority aging research. In this article, we describe the conceptual framework, logistical approaches, challenges, and lessons learned from our experience training junior investigators in methodology through the Michigan Center for Urban African American Aging Research over the past 20 years, with the goal of informing future analytic training efforts for the next generation of scholars focused on minority aging issues.


Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a.
The liver is a vital organ involving in various major metabolic functions in human body. MicroRNA-122 (miR-122) plays an important role in the regulation of liver metabolism, but its intrinsic physiological functions require further clarification. This study integrated the genome-scale metabolic model of hepatocytes and mouse experimental data with germline deletion of Mir122a (Mir122a-/-) to infer Warburg-like effects. Elevated expression of MiR-122a target genes in Mir122a-/-mice, especially those encoding for metabolic enzymes, was applied to analyze the flux distributions of the genome-scale metabolic model in normal and deficient states. By definition of the similarity ratio, we compared the flux fold change of the genome-scale metabolic model computational results and metabolomic profiling data measured through a liquid-chromatography with mass spectrometer, respectively, for hepatocytes of 2-month-old mice in normal and deficient states. The Ddc gene demonstrated the highest similarity ratio of 95% to the biological hypothesis of the Warburg effect, and similarity of 75% to the experimental observation. We also used 2, 6, and 11 months of mir-122 knockout mice liver cell to examined the expression pattern of DDC in the knockout mice livers to show upregulated profiles of DDC from the data. Furthermore, through a bioinformatics (LINCS program) prediction, BTK inhibitors and withaferin A could downregulate DDC expression, suggesting that such drugs could potentially alter the early events of metabolomics of liver cancer cells.


Fabrication of intraoral radiotherapy prostheses.
An accurate, short method of fabricating intraoral radiotherapy prostheses has been described. With it, there is no need of mounting casts on an articulator, wax-up, or flasking. Almost all procedures can be accomplished by the dental technician. Most important, the prostheses can be ready for use a few hours after the impressions are made. The technician can prepare the walls and cylinders beforehand and keep them in stock until needed. Also, it would be advisable for the radiotherapist to be present at the initial fastening of the bases to the cylinders. In this manner, the accuracy of the function of the prosthesis will be assured.


Mental illness and road traffic accidents.
One hundred psychiatric patients were carefully matched with 100 physically ill patients and their driving records compared. The psychiatric patients were consuming far greater quantities of psychotropic drugs and included a larger number of alcoholics and heavy drinkers. During the six months before admission there were no significant differences between the two groups of patients with respect to accident and traffic code infringements. Apart from individual patients, drugs did not appear to be influencing the outcome in statistical terms. Alcoholics and heavy drinkers showed an increased lifetime accident liability. No specific psychiatric diagnosis was otherwise associated with increased accident rates. The majority of accidents reported were relatively trivial.


Three synthetic routes to single-crystalline PbS nanowires with controlled growth direction and their electrical transport properties.
Single-crystalline rock-salt PbS nanowires (NWs) were synthesized using three different routes; the solvothermal, chemical vapor transport, and gas-phase substitution reaction of pregrown CdS NWs. They were uniformly grown with the [100] or [110], [112] direction in a controlled manner. In the solvothermal growth, the oriented attachment of the octylamine (OA) ligands enables the NWs to be produced with a controlled morphology and growth direction. As the concentration of OA increases, the growth direction evolves from the [100] to the higher surface-energy [110] and [112] directions under the more thermodynamically controlled growth conditions. In the synthesis involving chemical vapor transport and the substitution reaction, the use of a lower growth temperature causes the higher surface-energy growth direction to change from [100] to [110]. The high-resolution X-ray diffraction pattern and X-ray photoelectron spectroscopy results revealed that a thinner oxide-layer was produced on the surface of the PbS NWs by the substitution reaction. We fabricated field effect transistors using single PbS NW, which showed intrinsic p-type semiconductor characteristics for all three routes. For the PbS NW with a thinner oxide layer, the carrier mobility was measured to be as high as 10 cm(2) V(-1) s(-1).


Antibodies against oxidized low-density lipoprotein are associated with subclinical atherosclerosis in recent-onset rheumatoid arthritis.
Rheumatoid arthritis (RA) patients have increased mortality largely as a result of cardiovascular diseases (CVD) that cannot be explained by traditional risk factors, suggesting that systemic inflammation may accelerate atherosclerosis. We investigated the presence of subclinical atherosclerosis in early RA (<12 months) and the possible association of RA-related risk factors. Forty patients with early RA and 40 controls matched for age, sex, and traditional risk factors for CVD were selected. Carotid US examination, assay of lipogram, C-reactive protein (CRP), and oxidized low-density lipoprotein antibodies (OxLDL-ab) were done. RA patients had significantly higher carotid intima-media thickness (cIMT) values and more plaque than the control (P<0.001 and P=0.0122, respectively). CRP and OxLDL-ab were significantly higher in RA patients than controls. Traditional risk factors and RA-related risk factors (disease duration, DAS-28, duration of treatment with steroids, erythrocyte sedimentation rate, and CRP) as well as OxLDL and cIMT were significantly higher in RA with plaques compared to those without plaques. Regression analysis identified the age of patients, CRP, and OxLDL-ab as an independent risk factor associated with the presence of atherosclerosis. there is increased prevalence of carotid plaques in patients with recent-onset RA compared to matched controls. The accelerated atherosclerosis is predicted by age, CRP, and oxLDL-ab. The association of plaques with elevated CRP and OxLDL-ab support the hypothesis that chronic systemic autoimmune inflammatory process is probably a driving force for premature atherosclerosis.


Inhibitory Effect of PD-1/PD-L1 and Blockade Immunotherapy in Leukemia.
PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of a variety of solid tumors. Some clinical trials have also confirmed the excellent efficacy of PD- 1/PD-L1 inhibitors on lymphoma. However, the efficacy of PD-1/PD-L1 inhibitors on leukemia remains unclear. To understand the connection between PD-1/PD-L1 and leukemia better, this review concentrates on the up-regulated expression of PD-1/PD-L1 and the PD-1/PD-L1 blockade trials in participants with leukemia. PD-1/PD-L1 signal performs momentously negative immunoregulation of cancer, which can inhibit the activation of cytotoxic T cells and involve in the immune escape in tumors. Activated PD-1/PD-L1 may transduce negative intracellular signals to block the mitotic cycle and the development of T-cells. Several pathways are involved in these critical biochemical processes, including MAPK, calcium, PI3K/AKT, and so on. Lately, PD-1/PD-L1 antibodies have illustrated unprecedented curative effects on Hodgkin's lymphoma and some solid tumors. Specimens from patients with leukemia demonstrated the elevated level of PD-1/PD-L1 in T lymphocytes. This finding inspired hematologists to use PD-1/PD-L1 inhibitors for subjects suffering from leukemia. Some clinical trials have implied that PD-1/PD-L1 inhibitors could help patients fight against leukemia, however, other researchers have reported the opposite results. PD-1/PD-L1 is upregulated in leukemia, but the results regarding PD-1/PD-L1 blockade are mixed and more clinical trials are needed to be conducted.


Why do lower educated people continue smoking? Explanations from the longitudinal GLOBE study.
This article describes the effect of educational level on the decision to continue smoking among 1,354 initially smoking participants (age > or = 20 years) in the Dutch GLOBE study. The effect of education on continued smoking was explained from baseline information (1991) on smoking characteristics, individual characteristics, and environmental factors. Smoking status was reassessed after 6.5 years. Lower educated smokers more often continued smoking (odds ratio 2.09). Poor perceived health and earlier smoking initiation in lower educated groups were main predictors of educational differences in smoking maintenance. Educational differences in chronic illness, perceived control, neuroticism, and emotional support also contributed to the explanation of educational differences in continued smoking. These results have important implications for intervention programs and policy.


Delineating intra-tumoral heterogeneity and tumor evolution in breast cancer using precision-based approaches.
The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1 and BRCA2, and hormone receptors. However, even within each subtype, heterogeneity that is driven by underlying evolutionary mechanisms is suggested to underlie poor response to therapy, variance in disease progression, recurrence, and relapse. Intratumoral heterogeneity highlights that the evolvability of tumor cells depends on interactions with cells of the tumor microenvironment. The complexity of the tumor microenvironment is being unraveled by recent advances in screening technologies such as high throughput sequencing; however, there remain challenges that impede the practical use of these approaches, considering the underlying biology of the tumor microenvironment and the impact of selective pressures on the evolvability of tumor cells. In this review, we will highlight the advances made thus far in defining the molecular heterogeneity in breast cancer and the implications thereof in diagnosis, the design and application of targeted therapies for improved clinical outcomes. We describe the different precision-based approaches to diagnosis and treatment and their prospects. We further propose that effective cancer diagnosis and treatment are dependent on unpacking the tumor microenvironment and its role in driving intratumoral heterogeneity. Underwriting such heterogeneity are Darwinian concepts of natural selection that we suggest need to be taken into account to ensure evolutionarily informed therapeutic decisions.


Hip arthroscopy in the setting of hip arthroplasty.
Hip arthroscopy has traditionally been viewed as a hip preservation procedure performed in patients with native joint pathology. However, as the list of indications for arthroscopic hip intervention grows, further advances are expanding its use. The purpose of this systematic review was to examine existing evidence supporting the use of hip arthroscopy in the setting of hip arthroplasty. Using predetermined inclusion criteria, EMBASE, MEDLINE and PubMed were searched for articles addressing arthroscopic hip surgery performed in hips containing joint replacement arthroplasties. Inclusion criteria limited our search to human and English language studies addressing articles where clear surgical indications are described. Article screening was conducted in duplicate. Seven-hundred and forty-three studies were retrieved before duplicate screening, and 18 satisfied inclusion criteria. Eleven case series, six case reports and one prospective cohort study are included. In total, 171 patients underwent hip arthroscopy following previous arthroplasty. Indications for arthroscopy included iliopsoas tendinopathy (35.8%), symptomatic hips with no clear diagnosis despite extensive investigation (24.6%), periprosthetic infection (6.4%) and intra-articular loose bodies (3.5%). Almost all patients who underwent hip arthroscopy experienced positive outcomes from the procedure. Hip arthroscopy after hip arthroplasty is supported by our systematic review for a variety of indications. Hip arthroscopy can be a safe and effective method of treating hip arthroplasty patients with iliopsoas tendinopathy. Hip arthroscopy also has utility in patients with symptomatic hip arthroplasty despite exhaustion of other diagnostic avenues. A systematic review of level IV studies.


Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome.
3MC1 syndrome is a rare autosomal recessive disorder characterized by intellectual disability, short stature and distinct craniofacial, umbilical, and sacral anomalies. Five mutations in MASP1, encoding lectin complement pathway enzymes MASP-1 and MASP-3, have thus far been reported to cause 3MC1 syndrome. Only one previously reported mutation affects both MASP-1 and MASP-3, while the other mutations affect only MASP-3. We evaluated six unrelated individuals with 3MC1 syndrome and performed Sanger sequencing for all coding exons of MASP1. We also measured complement lectin and alternative pathway activities in an affected individual's serum. We found two novel splice site mutations, c.1012-2A > G in one and c.891 + 1G > T in two probands, and three novel missense mutations, c.1451G > A (p.G484E), c.1657G > A (p.D553N), and c.1987G > T (p.D663Y). Missense mutations affect only MASP-3, while splice site mutations affect both MASP-1 and MASP-3. In a proband who is homozygous for c.891 + 1G > T, we detected a total lack of lectin complement pathway activity and a 2.5-fold lower alternative pathway activity. The phenotype observed in patients whose both MASP-1 and MASP-3 are affected and in those whose only MASP-3 is affected does not appear to be different. We observed structural brain abnormalities, neonatal tooth, a vascular anomaly and a solid lesion in liver as novel phenotypic features of 3MC1 syndrome. Novel mutations and additional phenotypic features expand the genotypic and phenotypic spectrum of 3MC1 syndrome. Although patients with MASP-1 dysfunction in addition to disrupted MASP-3 have an altered complement system, their disease phenotype is not different from those having only MASP-3 dysfunction.


Evaluation of Uncertainties in the Anthropogenic SO2 Emissions in the USA from the OMI Point Source Catalog.
Satellite remote sensing is a promising method of monitoring emissions that may be missing in inventories, but the accuracy of these estimates is often not clear. We demonstrate here a comprehensive evaluation of errors in anthropogenic sulfur dioxide (SO2) emission estimates from NASA's OMI point source catalog for the contiguous US by comparing emissions from the catalog with high-quality emission inventory data over different dimensions including size of individual sources, aggregate vs individual source errors, and potential bias in individual source estimates over time. For sources that are included in the catalog, we find that errors in aggregate (sum of error for all included sources) are relatively low. Errors for individual sources in any given year can be substantial, however, with over- or underestimates in terms of total error ranging from -80 to 110 kt (roughly 10-90th percentile). We find that these errors are not necessarily random over time and that there can be consistently positive or negative biases for individual sources. We did not find any overall statistical relationship between the degree of isolation of a source and bias, either at a 40 or 70 km scales. For a sub-set of sources where inventory emissions over a radius of 70 km around an OMI detection are larger than twice the emissions within 40 km, the OMI value is consistently overestimated. We find, as expected, that emission sources not included in the catalog are the largest aggregate source of difference between the satellite estimates and inventories, especially in more recent years where source emission magnitudes have been decreasing and note that trends in satellite detections do not necessarily track trends in total emissions. We find that the OMI-based SO2 emissions are accurate in aggregate, when summed over a number of sources, but must be interpreted more cautiously at the individual source level. Similar analyses would be valuable for other satellite emission estimates; however, in many cases, the appropriate high-quality reference data may need to be generated.


Aspirin, but not propranolol, attenuates the acute stress-induced increase in circulating levels of interleukin-6: a randomized, double-blind, placebo-controlled study.
Psychosocial stress might increase the risk of atherothrombotic events by setting off an elevation in circulating levels of the proinflammatory cytokine interleukin (IL)-6. We investigated the effect of aspirin and propranolol on the responsiveness of plasma IL-6 levels to acute psychosocial stress. For 5 days, 64 healthy subjects were randomized, double-blind, to daily oral aspirin 100mg plus long-acting propranolol 80 mg, aspirin 100mg plus placebo, long-acting propranolol 80 mg plus placebo, or placebo plus placebo. Thereafter, all subjects underwent the 13-min Trier Social Stress Test, which combines a preparation phase, a job interview, and a mental arithmetic task. Plasma IL-6 levels were measured in blood samples collected immediately pre- and post-stress, and 45 min and 105 min thereafter. The change in IL-6 from pre-stress to 105 min post-stress differed between subjects with aspirin medication and those without (p =0.033; eta p2=0.059). IL-6 levels increased less from pre-stress to 105 min post-stress (p <0.027) and were lower (p =0.010) at 105 min post-stress in subjects with aspirin than in subjects without aspirin. The significance of these results was maintained when controlling for gender, age, waist-to-hip ratio, mean arterial blood pressure, and smoking status. Medication with propranolol was not significantly associated with the stress-induced change in IL-6 levels. Also, aspirin and propranolol did not significantly interact in determining the IL-6 stress response. Aspirin but not propranolol attenuated the stress-induced increase in plasma IL-6 levels. This suggests one mechanism by which aspirin treatment might reduce the risk of atherothrombotic events triggered by acute mental stress.


To serve and protect: The modulatory role of von Willebrand factor on factor VIII immunogenicity.
Hemophilia A is a bleeding disorder characterized by the absence or dysfunction of blood coagulation factor VIII (FVIII). Patients are treated with regular infusions of FVIII concentrate. In response to treatment, approximately 30% of patients with severe hemophilia A develop inhibitory antibodies targeting FVIII. Both patient and treatment related risk factors for inhibitor development have been described. Multiple studies comparing the immunogenicity of recombinant and plasma-derived FVIII have yielded conflicting results. The randomized controlled SIPPET (Survey of Inhibitors in Plasma-Product Exposed Toddlers) trial demonstrated an increased risk of inhibitor development of recombinant FVIII when compared to von Willebrand factor (VWF)-containing plasma-derived FVIII. Presently, it is unclear which mechanism underlies the reduced immunogenicity of plasma-derived FVIII. In this review we address the potential role of VWF on FVIII immunogenicity and we discuss how VWF affects the immune recognition, processing and presentation of FVIII. We also briefly discuss the potential impact of glycan-composition on FVIII immunogenicity. It is well established that VWF shields the uptake of FVIII by antigen presenting cells. We have recently shown that VWF binds to the surface of dendritic cells. Here, we present a novel model in which surface bound FVIII-VWF complexes regulate the internalization of FVIII. Binding of FVIII to VWF is critically dependent on sulfation of Tyr1699 (HVGS numbering) in the light chain of FVIII. Incomplete sulfation of Tyr1699 has been suggested to occur in several recombinant FVIII products resulting in a loss of VWF binding. We hypothesize that this results in alternative pathways of FVIII internalization by antigen presenting cells which are not regulated by VWF. This hypothetical mechanism may explain the reduced immunogenicity of VWF containing plasma-derived FVIII concentrates as found in the SIPPET study.


Targeting the transsulfuration-H2S pathway by FXR and GPBAR1 ligands in the treatment of portal hypertension.
Cirrhosis is a end-stage disease of the liver in which fibrogenesis, angiogenesis and distortion of intrahepatic microcirculation lead to increased intrahepatic resistance to portal blood flow, a condition known as portal hypertension. Portal hypertension is maintained by a variety of molecular mechanisms including sinusoidal endothelial cells (LSECs) hyporeactivity, activation of hepatic stellate cells (HSCs), reduction in hepatic endothelial nitric oxide synthase (eNOS) activity along with increased eNOS-derived NO generation in the splanchnic and systemic circulations. A reduction of the expression/function of the two major hydrogen sulfide (H2S)-producing enzymes, cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), has also been demonstrated. A deficit in the transsulfuration pathway leading to the accumulation of homocysteine might contribute to defective generation of H2S and endothelial hyporeactivity. Bile acids are ligands for nuclear receptors, such as farnesoid X receptor (FXR), and G-protein-coupled receptors (GPCRs), such as the G-protein bile acid receptor 1 (GPBAR1). FXR and GPBAR1 ligands regulate the expression/activity of CSE by both genomic and non-genomic effects and have been proved effective in protecting against endothelial dysfunction observed in rodent models of cirrhosis. GPBAR1, a receptor for secondary bile acids, is selectively expressed by LSECs and its activation increases the expression of CSE and attenuates the production of endotelin-1, a potent vasoconstrictor agent. In vivo GPBAR1 ligand attenuates the imbalance between vasodilatory and vaso-constricting agents, making GPBAR1 a promising target in the treatment of portal hypertension.


Experimental cryptorchidism in the adult mouse. III. Qualitative and quantitative electron microscopic morphology of Leydig cells.
The morphology of Leydig cells of control and 28-day-old cryptorchid mice was studied by electron microscopy and stereologic techniques. Leydig cell profiles of control mice were larger in section when compared to cryptorchid mice, but no differences were observed in the distribution of organelles in Leydig cells in the two groups. Quantitatively, the absolute volumes of smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), mitochondria, lysosomes, multivesicular bodies, peroxisomes, cytoplasmic matrix, nucleus, lipid droplets, membrane whorls, ribosomal aggregates, and annulate lamellae per Leydig cell were reduced significantly after 28 days of cryptorchidism. However, the absolute volumes of these organelles per testis were not significantly different between control and cryptorchid mice, due to the increase in Leydig cell number per testis in the cryptorchid testis, compared to the controls, except that the absolute volume of Golgi per Leydig cell was not significantly different between control and cryptorchid rats, but the absolute volume of Leydig cell Golgi was significantly lower in control rats. Based on these results, we conclude that, morphologically, a 28-day cryptorchid mouse Leydig cell clearly approximates a "half unit" of a control Leydig cell.


Electrocardiographic and further predictors for permanent pacemaker requirement after transcatheter aortic valve implantation.
The objective of this study was to identify electrocardiographic (ECG) and further predictors for atrioventricular (AV) block with a need for pacemaker (PM) implantation after transcatheter aortic valve implantation (TAVI). Pre- and post-procedural ECGs of patients with severe aortic stenosis and ongoing TAVI were investigated in a prospective study. From 50 consecutive patients enrolled in the study (mean age 80 +/- 6 years, 46% men), 17 (34%) experienced an AV block with subsequent requirement of a permanent PM [16 of 36 (44.4%) with CoreValve System and 1 of 14 (7.1%) with Edwards Sapiens System]. In patients with right bundle branch block (RBBB), PM implantation had to be performed more frequently [6 of 6 (100%) with CoreValve System and none with Edwards Sapiens System], P = 0.005. An AV block (Mobitz II second degree and third degree) occurred mostly within the first 24 h (range: Days 0-13) after the index procedure. No recovery of AV conduction with a change in PM indication occurred in a mean follow-up time of 13 +/- 6 days. Our data demonstrate that patients with pre-operative RBBB and those receiving CoreValve prosthesis are at a significantly higher risk for PM implantation after TAVI. Therefore, patients with the presence of RBBB before TAVI may be at lower risk for PM implantation using the Edwards Sapiens System.


Salt, Hypertension, and the Lens.
Salt is important in the pathogenesis of hypertension (HT). Salt-sensitive hypertension (SSH) accounts for about half of all HT cases. In SSH, sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) activity is impaired. Impaired Na+/K+-ATPase activity in the lens epithelium results in cortical opacities in the peripheral equator of the lens. We investigated the sensitivity of cortical lens opacities in detecting SSH. The study included 191 SSH and 159 non-SSH, salt-resistant HT (SRH) patients (350 HT patients total), aged 40-80 years. One hundred twenty-four sex- and age-matched patients without a HT diagnosis made up the control group. Daily salt intake of all groups was calculated from 24-hr urinary Na excretion. SSH was diagnosed when the difference in mean arterial blood pressure values obtained during high- and low-Na diets was ≥10%. Non-SSH, SRH was diagnosed when the difference was <10%.Two researchers examined the presence of cortical lens opacities biomicroscopically using the diffuse, direct, Scheimpflug, and retroillumination from fundus methods. Total lens opacity was predictive of SSH among all cases (P < 0.001), with a sensitivity and specificity of 75.4% [95% confidence interval (CI): 68.6-81.3] and 83.6% (95% CI: 77.0-89.0), respectively. Its positive and negative predictive values were 84.7% (95% CI: 79.4-88.8) and 73.9% (95% CI: 68.6-78.5), respectively. Lens opacities can be used as a finding that can be easily observed in the detection of SSH and excess salt intake.


[Prevention of Catheter-Associated Urinary Tract Infections].
With a share of 22.4%, nosocomial urinary tract infections (nUTIs) are among the most frequent infections acquired in hospitals, along with surgical site infections (24.7%), pneumonia (21.5%), clostridium difficile infections (6.6%) and primary sepsis (6%) 1. 80% of all nUTIs are associated with indwelling urinary catheters, with 12-16% of all hospitalised patients and up to 81.8% of all intensive care patients receiving an indwelling urinary catheter during their hospital stay 2 3. Therefore, profound knowledge about the basics of catheter-associated nUTIs and the correct management of urinary catheters are of utmost individual and socio-economic importance 4 5. It is estimated that up to 70% of all nUTIs occurring in Germany may be avoided by using appropriate preventative measures 6 7.In 2012, the authors Conway and Larson compared 8 recommendations in English language for the prevention of UTIs and noticed that they have been largely consistent over a period of 30 years 8. Special issues have rarely been addressed in valid studies, and study results are rather heterogeneous. For example, the 2008 SHEA (Society of Hospital Epidemiologists of America) guideline contains only 3 recommendations and 4 prohibitions which are based on more than one randomised controlled clinical study 9 10 11.The confirmed recommendations on the prevention of UTIs are consistent in the following aspects 12 13 14 15 16 17: · Every insertion of a urinary catheter must be based on a well-founded medical indication.. · Well-founded medical indications include acute urinary retention, interventions lasting several hours with a high fluid turnover, surgery involving the urinary tract, the necessity to record fluid turnover especially in critically ill patients, comfort for the dying, facilitating wound healing in the external genitals in the presence of urinary incontinence. Examples of unnecessary use of urinary catheters include prescriptions based on urinary incontinence alone and prolongation of use, e. g. after surgical procedures or after intensive care monitoring/recording has been completed.. · The insertion technique as well as catheter care and the detection of catheter-associated complications must be trained continuously.. · Catheterisation must be performed under sterile precautions.. · Only sterile and closed urinary drainage systems may be used.. · Catheters must be removed as early as possible..


Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters.
Neonatal jaundice that occurs in ABO or Rhesus issoimunisation has been recognized as one of the major risk factors for development of severe hyperbilirubinemia and bilirubin neurotoxicity. Aim of our study was to investigate clinical and laboratory parameters associated with hemolytic jaundice due to Rh and ABO incompatibility and compare results with the group of unspecific jaundice. One hundred sixty seven (167) neonatal hyperbilirubinemia cases were included in the study, 24.6% of which presented with ABO/Rhesus type hemolytic jaundice, and the rest with unspecific jaundice. Evaluation included: blood count, reticulocites, serum bilirubin, aminotransferases, blood grouping, and Coombs test, also the day of bilirubin peak, duration of the hyperbilirubinemia, and additional bilirubin measurements. We showed significantly lower mean values of hemoglobin, erythrocytes and hematocrit and significantly higher values of reticulocytes in the group of ABO/Rh incompatibility compared to the group of jaundice of unspecific etiology; also an earlier presentation and a higher-grade jaundice in this group. The laboratory profile in ABO/Rh isoimmunisation cases depicts hemolytic mechanism of jaundice. These cases carry a significant risk for early and severe hyperbilirubinemia and are eligible for neurodevelopmental follow-up. Hematological parameters and blood grouping are simple diagnostic methods that assist the etiological diagnosis of neonatal hyperbilirubinemia.


Prevalence of Attention Deficit Hyperactivity Disorder Symptoms in Children Who Were Treated at Emergency Service due to Unintentional Injury.
Attention Deficit Hyperactivity Disorder (ADHD) is a developmental disorder characterized by severe inattention, hyperactivity, and impulsivity. This research aims to determine the frequency of ADHD symptoms in children who were treated in emergency paediatric services due to unintentional injuries. This study was carried out with children who were treated due to unintentional injuries in an Emergency Department. ADHD symptoms were evaluated using the DSM-IV-based Screening and Assessment Scale for Behavioural Disorders in Children and Adolescents. The study sample consisted of 89 girls (40.1%) and 133 boys (59.9%)-a total of 222 children. The participants ranged from 5 to 18 years of age, and the mean age was found to be 11.5±3 years. According to medical evaluations, the most common diagnosis for the unintentional injuries was soft tissue trauma (41.9%). The mean ADHD and ODD (Oppositional Defiant Disorder) scores of our study sample were, respectively, 19.9±12 and 7.7±5.7. The prevalence of children with possible ADHD was as high as 81.6% (179) and, for ODD, was 62.6% (139), according to cut-off values. Our results pointed out very high levels of ADHD and ODD symptoms among children who were treated at emergency services for accidental injuries. Appropriately screening for ADHD in children with accidental injuries and referring them to child psychiatry units may prevent later accidents and injuries.


Innovation and Integrity: Desiderata and Future Directions for Prevention and Intervention Science.
This article summarizes essential implications of the papers within this special issue and discusses directions for future prevention and intervention research on conceptual issues, methodological and transfer-related challenges and opportunities. We identify a need to move from programs to principles in intervention research and encourage the implementation of research on potential mechanisms underlying intervention effectiveness. In addition, current methodological issues in intervention research are highlighted, including advancements in methodology and statistical procedures, extended outcome assessments, replication studies, and a thorough examination of potential biases. We further discuss transfer-related issues, for example the need for more research on the flexibility and adaptability of programs and intervention approaches as well as more general problems in knowledge translation reasoning the need for enhanced communication between practitioners, policy makers, and researchers. Finally, we briefly touch on the need to discuss the relation between single intervention programs, the mental health system, and changes of contextual conditions at the macro level.


Expression and processing of small integrin-binding ligand N-linked glycoproteins in mouse odontoblastic cells.
Small integrin-binding ligand N-linked glycoproteins (SIBLINGs) are expressed in dentin and believed to control dentinogenesis. Five members of SIBLING family include bone sialoprotein (BSP), osteopontin (OPN), matrix extracellular phosphoglycoprotein (MEPE), dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP). These genes are clustered on chromosome 4q in humans and share similar biological features. DSPP and DMP1 are processed into given structural/functional fragments in rat and porcine. It still remains unclear whether these evidences occur in mouse and other SIBLING members are also processed into given fragments from their parent precursors. The aim of this study was to identify expression and processing of the five proteins in two mouse odontoblastic cell lines. Two mouse odontoblastic cells were used to study expression and processing of the five SIBLING proteins by immunohistochemistry and Western blot analyses. Immunohistochemistry study showed that all of the five SIBLING members were expressed within the cytoplasm and cellular processes in the mouse odontoblastic cell lines. Expression levels of DMP1 and DSPP were higher in differentiated mouse odontoblasts than undifferentiated mouse odontoblasts. Immunolabelling signal of DSP and MEPE was also detected within the nucleus in the two cell lines. Western blot assay indicated that all five members were processed into at least two fragments in these cells. These results suggest that different processed products and expression levels of the SIBLING proteins may play distinct biological functions in tooth development and mineralisation.


Transcriptomic and Metabolomic Analyses Reveal Differences in Flavonoid Pathway Gene Expression Profiles between Two Dendrobium Varieties during Vernalization.
Dendrobium (Orchidaceae, Epidendoideae) plants have flowers with a wide variety of colors that persist for a long period throughout the year. The yellow coloration of Dendrobium flowers is mainly determined by the flavonol pathway and the flavone pathway, but the relevant biosynthesis mechanisms during vernalization remain unclear. To explore the similarities and differences in flavonoid biosynthesis in different tissues during vernalization, we selected two species of Dendrobium for a flower color study: Dendrobium capillipes Rchb (which has yellow flowers) and Dendrobium nobile Lindl (which has white flowers). We collected a total of 36 samples from six tissue types and both Dendrobium species during vernalization and subjected the samples to metabolic profiling and transcriptome sequencing. A total of 31,504 differentially expressed genes (DEGs) were identified between different tissues of the two Dendrobium species by transcriptomic analysis. However, many differentially accumulated metabolites (DAMs) and DEGs were enriched not only in the general pathway of "flavonoid biosynthesis" but also in multiple subpathways of "flavone and flavonol biosynthesis". According to a combined transcriptome and metabolome analysis, Putrescine hydroxycinnamoyl transferase 1 (LOC110093422) may be the main gene responsible for the differences in flavonoid accumulation during vernalization, which is closely associated with yellow flowers. Taken together, the results of our study preliminarily revealed the metabolites responsible for and the key genes regulating flavonoid biosynthesis during vernalization. These results provide a basis for the further study of the molecular mechanism of flavonoid synthesis during vernalization.


Intensified strategies to control vancomycin-resistant enterococci in immunocompromised patients.
Increasing colonization and infection with vancomycin-resistant enterococci (VRE) in immunocompromised patients are associated with increased mortality. Despite contact precautions for VRE control, rapid limitation of its spread is often impossible. We report on a VRE outbreak in a hematologic/oncologic unit including 33 patients. Although 28 of the patients had only VRE colonization, VRE-related infection was probable in 4 patients, and VRE infection of the bloodstream occurred in 1 case. Two patients were identified by VRE screening on admission, 20 were identified by weekly routine VRE screening, and 6 were identified from specimens taken to clarify infections (eg, urine, bronchoalveolar lavage). Five individuals acquired VRE colonization as inpatients (contact patients). Multiple-locus variable-number tandem repeat analysis (MLVA) proved that the outbreak was caused by VanA gene-positive Enterococcus faecium belonging to MLVA genogroup C1(MLVA types 1, 7, 12). The outbreak strains exhibited the potential virulence factor esp(enterococcus surface protein). The outbreak was terminated within 2 months by intensified infection-control measures, including quarantine and the cohorting of patients who tested positive for VRE; however, VRE spread recurred after the measures were discontinued but was again limited by resuming the measures. We conclude that intensive infection-control strategies enable the timely termination of VRE outbreaks, even those involving VRE strains with high epidemic potential on "high-risk wards" (eg, hematologic/oncologic units). Premature discontinuation of infection-control measures may cause recurrence of the VRE spread.


STAT3 pathway in cancers: Past, present, and future.
Signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, discovered in the cytoplasm of almost all types of mammalian cells, plays a significant role in biological functions. The duration of STAT3 activation in normal tissues is a transient event and is strictly regulated. However, in cancer tissues, STAT3 is activated in an aberrant manner and is induced by certain cytokines. The continuous activation of STAT3 regulates the expression of downstream proteins associated with the formation, progression, and metastasis of cancers. Thus, elucidating the mechanisms of STAT3 regulation and designing inhibitors targeting the STAT3 pathway are considered promising strategies for cancer treatment. This review aims to introduce the history, research advances, and prospects concerning the STAT3 pathway in cancer. We review the mechanisms of STAT3 pathway regulation and the consequent cancer hallmarks associated with tumor biology that are induced by the STAT3 pathway. Moreover, we summarize the emerging development of inhibitors that target the STAT3 pathway and novel drug delivery systems for delivering these inhibitors. The barriers against targeting the STAT3 pathway, the focus of future research on promising targets in the STAT3 pathway, and our perspective on the overall utility of STAT3 pathway inhibitors in cancer treatment are also discussed.


Adult Multicystic Nephroma: Case Report and Review of the Literature.
Multicystic nephroma (MCN) is relatively a rare, nongenetic and benign lesion of the kidney which has a bimodal distribution. The congenital form is commonly seen under the age of 2. Adult-onset MCN is more often seen in women, especially in post menopausal females. The aetiopathogenesis of MCN is still unknown. Ovarian-like stroma of the tumour indicates the tumour originates from the mullerian tissue of the kidney. Hormonal theory is suggestive as the stroma of the tumour is positive for estrogen and progesteron. Preoperative diagnosis of MCN is difficult. Surgical approach is recommended both for the histological diagnosis and the treatment of the disease. We here present a 53-year-old female patient with MCN admitted to the urology clinic with left flank pain treated successfully with partial nephrectomy. No recurrence was noted after six months of clinical and radiological follow-up.


A team-based approach to qualitative inquiry: the collaborative retreat.
A team of researchers undertook a collaborative qualitative study to explore beginning dietitians' life experiences and the meaning ascribed to those experiences in the context of dietetic practice. Data were collected using Seidman's three-step in-depth phenomenological interviewing method with 12 beginning dietitians who were graduates of the three participating dietetic programs. We outline the collaborative research process and highlight a writing and data analysis technique described as the collaborative retreat, a face-to-face, two-day gathering that facilitated the researchers' collective decision-making and organization, discussion, and analysis of this complex qualitative data set. Use of a listening guide aided researchers' understanding and interpretation of participant voices. Researchers concluded that the overall collaborative qualitative research process was positive and self-fulfilling, and that it resulted in multiple benefits for them individually and the research project collectively. Researchers were able to work through methodological and theoretical issues as these arose, with the assistance of technology, writing, listening, and dialogue. Relationship building and relationship maintenance emerged as factors critical to the success of the research process. Collaborative research teams that are committed to listening, writing, and dialogue will find that the collaborative retreat can be a productive site of knowledge generation and mentorship.


Intrusive growth of flax phloem fibers is of intercalary type.
Flax (Linum usitatissimum L.) phloem fibers elongate considerably during their development and intrude between existing cells. We questioned whether fiber elongation is caused by cell tip growth or intercalary growth. Cells with tip growth are characterized by having two specific zones of cytoplasm in the cell tip, one with vesicles and no large organelles at the very tip and one with various organelles amongst others longitudinally arranged cortical microtubules in the subapex. Such zones were not observed in elongating flax fibers. Instead, organelles moved into the very tip region, and cortical microtubules showed transversal and helical configurations as known for cells growing in intercalary way. In addition, pulse-chase experiments with Calcofluor White resulted in a spotted fluorescence in the cell wall all over the length of the fiber. Therefore, it is concluded that fiber elongation is not achieved by tip growth but by intercalary growth. The intrusively growing fiber is a coenocytic cell that has no plasmodesmata, making the fibers a symplastically isolated domain within the stem.


Design of Miniature Ultrawideband Active Magnetic Field Probe Using Integrated Design Idea.
This article presents a miniature ultrawideband active magnetic probe which is composed of a passive structure and an active amplification circuit structure. The active circuit mainly contains two chips, specifically an amplification chip (HMC797APM5E) and a power management chip (HMC980LP4E). The maximum size of the probe is no more than 64 × 41.5 mm2. Compared with the passive probe with the same-sized loop, the sensitivity of the proposed probe is enhanced by 25 dB through the active circuit design. The working frequency bandwidth of the proposed probe can cover 9 kHz to 18 GHz. Additionally, the flatness is about ±4 dB in terms of |S21| in the stable working bandwidth. It is efficient for high-frequency near-field scanning.


Molecular Mechanisms Involved in Schwann Cell Plasticity.
Schwann cell incredible plasticity is a hallmark of the utmost importance following nerve damage or in demyelinating neuropathies. After injury, Schwann cells undergo dedifferentiation before redifferentiating to promote nerve regeneration and complete functional recovery. This review updates and discusses the molecular mechanisms involved in the negative regulation of myelination as well as in the reprogramming of Schwann cells taking place early following nerve lesion to support repair. Significant advance has been made on signaling pathways and molecular components that regulate SC regenerative properties. These include for instance transcriptional regulators such as c-Jun or Notch, the MAPK and the Nrg1/ErbB2/3 pathways. This comprehensive overview ends with some therapeutical applications targeting factors that control Schwann cell plasticity and highlights the need to carefully modulate and balance this capacity to drive nerve repair.


Mandibular third molar removal: patient preferences, assessments of oral surgeons and patient flows.
Mandibular third molar removal is one of the most common treatments conducted at oral and maxillofacial surgery clinics in Sweden. During the 1980's and 1990's, 20-25,000 mandibular third molars were removed annually which represents about 60% of the total operation volume. Removals performed in private specialist clinics and general dental clinics are not included in these figures. The aims of the present studies on mandibular third molars were to: 1) study values that reflect patients' preferences about possible outcomes of removal and non-removal; 2) make comparisons between Sweden and Wales with respect to patient's preferences; 3) study assessments of oral surgeons' indications for molars to be removed; 4) describe patient flows in the care process of removal. The multi-attribute utility (MAU) method was used to quantify patients' preferences about outcomes following removal and non-removal. Whilst there were clear cultural and economic differences between the Swedish and the Welsh, there was a high degree of correlation in patients' ranking of the different outcomes for patients from the two countries (rs = 0.93, P<0.001). Generally, situations describing the outcomes of non-removal had a higher ranking than those describing the outcomes of removal i.e. patients seemed to prefer non-removal. Oral surgeons at seven specialist clinics registered data for 666 patients i.e. patient age and sex, the angular position and extent of eruption of the molar and whether or not there was an associated disease related to the molar proposed for removal. The indication for the removal was assessed on a Visual Analogue Scale (VAS), and the recorded results found to show a great variety. The mean VAS for removal of molars without disease was significantly lower than that for molars with associated disease. The differences between the mean VAS for molars with one disease compared with molars with two or three diseases were not significant. The patients' age was the only factor that had a significant effect on the assessment of the indication for molars without disease. The indication was higher for patients of the youngest age group than for patients of the oldest age group (P<0.05). In four specialist units in southern Sweden, the patient flows (the number of visits and what the visits comprise of) was registered for 361 patients. All details were recorded from arrival of the referral to the unit to performed mandibular third molar surgery. Eight different patient flows were found. The number of patient visits varied from one to three. For about 60 percent of the patients, attached radiographs to the referral were considered not appropriate and had to be completed, e.g. to be retaken. For a minority of the patients, the radiographic examination was completed at the radiological clinic included in the specialist unit and, in the oral and maxillofacial clinic for the others. The number of patient visits seemed not to depend on whether the attached radiographs were judged to be appropriate or not. Patient preferences seem to be more stable than the preferences of oral surgeons across the boundaries. Patients prefer outcomes of third molar non-removal as compared to outcomes following removal. Different patient flows may influence the cost-effectiveness in mandibular third molar surgery.


Founder myoblasts and fibre number during adult myogenesis in Drosophila.
We have examined the mechanisms underlying the setting of myotubes and choice of myotube number in adult Drosophila. We find that the pattern of adult myotubes is prefigured by a pattern of duf-lacZ-expressing myoblasts at appropriate locations. Selective expression of duf-lacZ in single myoblasts emerges from generalized, low-level expression in all adult myoblasts during the third larval instar. The number of founders, thus chosen, corresponds to the number of fibres in a muscle. In contrast to the embryo, the selection of individual adult founder cells during myogenesis does not depend on Notch-mediated lateral inhibition. Our results suggest a general mechanism by which multi-fibre muscles can be patterned.


MECE: a method for enhancing the catalytic efficiency of glycoside hydrolase based on deep neural networks and molecular evolution.
The demand for high efficiency glycoside hydrolases (GHs) is on the rise due to their various industrial applications. However, improving the catalytic efficiency of an enzyme remains a challenge. This investigation showcases the capability of a deep neural network and method for enhancing the catalytic efficiency (MECE) platform to predict mutations that improve catalytic activity in GHs. The MECE platform includes DeepGH, a deep learning model that is able to identify GH families and functional residues. This model was developed utilizing 119 GH family protein sequences obtained from the Carbohydrate-Active enZYmes (CAZy) database. After undergoing ten-fold cross-validation, the DeepGH models exhibited a predictive accuracy of 96.73%. The utilization of gradient-weighted class activation mapping (Grad-CAM) was used to aid us in comprehending the classification features, which in turn facilitated the creation of enzyme mutants. As a result, the MECE platform was validated with the development of CHIS1754-MUT7, a mutant that boasts seven amino acid substitutions. The kcat/Km of CHIS1754-MUT7 was found to be 23.53 times greater than that of the wild type CHIS1754. Due to its high computational efficiency and low experimental cost, this method offers significant advantages and presents a novel approach for the intelligent design of enzyme catalytic efficiency. As a result, it holds great promise for a wide range of applications.


Differences in Cardiorespiratory Fitness between Chinese and Japanese Children and Adolescents.
This study aimed to compare the difference in cardiorespiratory fitness between Chinese and Japanese children and adolescents. Participants comprised 9025 children and adolescents aged 7-18 years from China and Japan. Cardiorespiratory fitness (CRF) was measured by performance in the 20 m shuttle run test (20mSRT) and estimated maximal oxygen consumption (VO2max). Differences in CRF between countries were evaluated by t-tests. Centile curves for the 20mSRT and VO2max values were constructed for Chinese and Japanese children and adolescents, respectively, using the Lambda Mu and Sigma (LMS) method. (1) For most of the age groups, the 20mSRT and VO2max performances among Chinese participants were lower than among Japanese participants. (2) Japanese children had the most apparent gains in P10, P50, and P90 VO2max values in primary school; however, they gradually decreased in middle school. For Chinese girls, the P10, P50, and P90 VO2max values decreased gradually with age. (3) The VO2max value among Japanese children increased; however, it decreased or remained flat among Chinese children in primary school. CRF among Chinese participants was lower than among Japanese participants while the VO2max value showed different trends in primary school. Effective measures should be taken to improve CRF among children and adolescents.


WWP2 and its association with PTEN in endometrial cancer.
We wished to determine if WWP2 gene expression and PTEN protein levels inversely correlate in human endometrial cancer tissues. Fifty-one endometrioid endometrial tumors and five normal endometrial controls were available for analysis. PTEN protein levels were assessed by immunohistochemistry (IHC). WWP2 and PTEN gene expression were quantitated by RT PCR. Clinical and pathologic information was collected by chart review. We found that in tumors with low PTEN protein but normal mRNA expression there were significantly higher levels of WWP2 expression (p = 0.0017). Increased WWP2 expression was not associated with clinical prognostic factors including lymphovascular space invasion, ≥ 50% myometrial invasion, grade, stage or recurrence. WWP2 expression was not different statistically between tumors and normal controls (p = NS). Therefore, in this cohort, tumors with low PTEN protein but normal mRNA expression had elevated levels of WWP2 expression. This suggests that WWP2 may be playing a role in PTEN degradation in endometrial cancer.


An entirely reverse-engineered finite element model of a classical guitar in comparison with experimental data.
The classical guitar is a popular string instrument in which the sound results from a coupled mechanical process. The oscillation of the plucked strings is transferred through the bridge to the body, which acts as an amplifier to radiate the sound. In this contribution, a procedure to create a numerical finite element (FE) model of a classical guitar with the help of experimental data is presented. The geometry of the guitar is reverse-engineered from computed tomography scans to a very high level of detail, and care is taken in including all necessary physical influences. All of the five different types of wood used in the guitar are modeled with their corresponding orthotropic material characteristics, and the fluid-structure interaction between the guitar body and the enclosed air is taken into account by discretizing the air volume inside the guitar with FEs in addition to the discretization of the structural parts. Besides the numerical model, an experimental setup is proposed to identify the modal parameters of a guitar. The procedure concludes with determining reasonable material properties for the numerical model using experimental data. The quality of the resulting model is demonstrated by comparing the numerically calculated and experimentally identified modal parameters.


Mutational landscape of intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is a fatal primary liver cancer (PLC) that affects 5-10% of all PLCs. Here we sequence tumour and matching control sample pairs of a large cohort of 103 ICC patients in China, resulting in the identification of an ICC-specific somatic mutational signature that is associated with liver inflammation, fibrosis and cirrhosis. We further uncover 25 significantly mutated genes including eight potential driver genes (TP53, KRAS, IDH1, PTEN, ARID1A, EPPK1, ECE2 and FYN). We find that TP53-defective ICC patients are more likely to be HBsAg-seropositive, whereas mutations in the oncogene KRAS are nearly exclusively found in HBsAg-seronegative ICC patients. Three pathways (Ras/phosphatidylinositol-4,5-bisphosphate 3-kinase signalling, p53/cell cycle signalling and transforming growth factor-β/Smad signalling), genes important for epigenetic regulation and oxidative phosphorylation are substantially affected in ICC. We reveal mutations in this study that may be valuable for designing further studies, better diagnosis and effective therapies.


Paper-tape occlusion of anthralin paste. A new outpatient therapy for psoriasis.
We present a new method for the outpatient use of anthralin paste in the treatment of psoriasis. By instructing the patient to cover the nightly paste application with semipermeable paper tape, we devised a practical and easy method for home therapy. In a study of 12 patients with unresponsive plaque-type psoriasis, six responded with 90% or better clearing of treated sites and two with 70% clearing, compared with symmetrical control sites. Four patients showed no substantial improvement. The average duration of therapy was 11 weeks. A three-month reevaluation of the conditions of these patients disclosed that improvement had been substantially maintained. Despite the tape occlusion, irritation was a manageable problem, except in three patients who had to halt therapy. Although less effective than conventional inpatient anthralin paste regimens, this method is more cost-effective for those with limited plaque disease.


HIV Myocarditis Presenting as Acute ST-Segment Elevation Myocardial Infarction.
Myocarditis is a common occurrence among patients infected with human immunodeficiency virus (HIV). However, it is rare to find HIV-associated myocarditis presenting as ST-segment elevation myocardial infarction with cardiogenic shock. A case of HIV-related myocarditis presenting as an acute inferolateral wall myocardial infarction in a 32-year-old male is described.


Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation.
Poly(ADP-ribose) polymerase 1 (PARP-1) and p53 are two key proteins in the DNA-damage response. Although PARP-1 is known to poly(ADP-ribosyl)ate p53, the role of this modification remains elusive. Here, we identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage. PARP-1 becomes super-activated by binding to damaged DNA, which in turn poly(ADP-ribosyl)ates p53. The nuclear export machinery is unable to target poly(ADP-ribosyl)ated p53, promoting accumulation of p53 in the nucleus where p53 exerts its transactivational function.


Cold and Heat Stress Diversely Alter Both Cauliflower Respiration and Distinct Mitochondrial Proteins Including OXPHOS Components and Matrix Enzymes.
Complex proteomic and physiological approaches for studying cold and heat stress responses in plant mitochondria are still limited. Variations in the mitochondrial proteome of cauliflower (Brassica oleracea var. botrytis) curds after cold and heat and after stress recovery were assayed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) in relation to mRNA abundance and respiratory parameters. Quantitative analysis of the mitochondrial proteome revealed numerous stress-affected protein spots. In cold, major downregulations in the level of photorespiratory enzymes, porine isoforms, oxidative phosphorylation (OXPHOS) and some low-abundant proteins were observed. In contrast, carbohydrate metabolism enzymes, heat-shock proteins, translation, protein import, and OXPHOS components were involved in heat response and recovery. Several transcriptomic and metabolic regulation mechanisms are also suggested. Cauliflower plants appeared less susceptible to heat; closed stomata in heat stress resulted in moderate photosynthetic, but only minor respiratory impairments, however, photosystem II performance was unaffected. Decreased photorespiration corresponded with proteomic alterations in cold. Our results show that cold and heat stress not only operate in diverse modes (exemplified by cold-specific accumulation of some heat shock proteins), but exert some associations at molecular and physiological levels. This implies a more complex model of action of investigated stresses on plant mitochondria.


Rationale for Determining the Functional Potency of Mesenchymal Stem Cells in Preventing Regulated Cell Death for Therapeutic Use.
Mesenchymal stem (stromal) cells (MSCs) are being investigated for treating degenerative and inflammatory disorders because of their reparative and immunomodulatory properties. Intricate mechanisms relate cell death processes with immune responses, which have implications for degenerative and inflammatory conditions. We review the therapeutic value of MSCs in terms of preventing regulated cell death (RCD). When cells identify an insult, specific intracellular pathways are elicited for execution of RCD processes, such as apoptosis, necroptosis, and pyroptosis. To some extent, exacerbated RCD can provoke an intense inflammatory response and vice versa. Emerging studies are focusing on the molecular mechanisms deployed by MSCs to ameliorate the survival, bioenergetics, and functions of unfit immune or nonimmune cells. Given these aspects, and in light of MSC actions in modulating cell death processes, we suggest the use of novel functional in vitro assays to ensure the potency of MSCs for preventing RCD. Such analyses should be associated with existing functional assays measuring the anti-inflammatory capabilities of MSCs in vitro. MSCs selected on the basis of two in vitro functional criteria (i.e., prevention of inflammation and RCD) could possess optimal therapeutic efficacy in vivo. In addition, we underline the implications of these perspectives in clinical studies of MSC therapy, with particular focus on acute respiratory distress syndrome. Stem Cells Translational Medicine 2017;6:713-719.


Why power matters: creating a foundation of mutual support in couple relationships.
Research shows that equal power helps couples create intimacy and relationship success. However, though couples increasingly desire equal relationships, cultural models of mutual support are not well developed. Clinicians often approach heterosexual couple therapy as though partners are inherently equal, thus reinforcing unacknowledged gender inequities. This article examines research that shows why power imbalances are destructive to intimate relationships and focuses on four gender-related aspects of mutual support: (a) shared relational responsibility, (b) mutual vulnerability, (c) mutual attunement, and (d) shared influence. Case examples illustrate how socio-emotional attunement, interrupting the flow of power, and introducing alternative relational experience help couple therapists identify and address power disparities in these important relational processes. Encouraging the powerful person to take relational initiative and introducing alternative gender discourse are especially important.


Acupuncture related acute purulent pericarditis masquerading uremic pericarditis.
We are reporting a rare case of acupuncture-related acute pericarditis in an old-aged gentleman due to Staphylococcus aureus infection who was successfully managed with drainage of pericardial fluid and broad-spectrum antibiotics. We also reviewed the literature and found cardiac tamponade as the most common acupuncture-related cardiac complication, followed by infective endocarditis, bacterial abscess, and infected myxoma. There was no available literature on post-acupuncture acute pericarditis.