Cardiac risk stratification in patients with congestive heart failure: a catecholamines-beta-adrenoceptor-cAMP pathway.
To investigate the stratification risk of catecholamines-beta-adrenoceptor (beta-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes beta-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. The period between the initial entry and the last follow-up measurement were 51 +/- 16 months, the total duration of clinical follow-up after the last measurement were 14 +/- 8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd x mg(-1) x pro(-1) from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd x mg(-1) x pro(-1) (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the beta-AR density below and above median. Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.


Role of geographic characteristics in the spatial cluster detection of cancer: Evidence in South Korea, 1999-2013.
Identification of high-risk areas of cancer, referred to as spatial clusters, can inform targeted policies for cancer control. Although cancer cluster detection could be affected by various geographic characteristics including sociodemographic and environmental factors which impacts could also vary over time, studies accounting for such influence remain limited. This study aims to assess the role of geographic characteristics in the spatial cluster detection for lung and stomach cancer over an extended period. We obtained sex-specific age-standardized incidence and mortality rates of lung and stomach cancer as well as geographic characteristics across 233 districts in South Korea for three five-year periods between 1999 and 2013. We classified geographic characteristics of each district into four categories: demography, socioeconomic status, behaviors, and physical environments. Specifically, we quantified physical environments using measures of greenness, concentrations of particulate matter and nitrogen dioxide, and air pollution emissions. Finally, we conducted cluster detection analyses using weighted normal spatial scan statistics with the residuals from multiple regression analyses performed with the four progressive sets of geographic attributes. We found that the size of clusters reduced as we progressively adjusted for geographic covariates. Among the four categories, physical environments had the greatest impact on the reduction or disappearance of clusters particularly for lung cancer consistently over time. Whereas older population affected a decrease of lung cancer clusters in the early period, the contribution of education was large in the recent period. The impact was less clear in stomach cancer than lung cancer. Our findings highlight the importance of geographic characteristics in explaining the existing cancer clusters and identifying new clusters, which jointly provides practical guidance to cancer control.


Laparoscopic Anatomical Liver Resection of Segment VIII by Using ICG Fluorescence Positive Staining Under the Guidance of Laparoscopic Ultrasonography.
Anatomical segmentectomy is a surgical procedure that completely removes a territory (or territories) of the third-order portal venous branches of a Couinaud segment (Wakabayashi et al. in J Hepatobil Pancreat Sci 29(1):82-98, 2022. https://doi.org/10.1002/jhbp.899 ). Laparoscopic segmentectomy of S8 is considered technically challenging because of the Precise dissection of the Glissonean pedicle of S8, and exposure of the middle and right hepatic veins are required (Ome et al. in J Am Coll Surg 230(3):e13-e20, 2020; Wakabayashi et al. in Ann Surg 261(4):619-29, 2015. https://doi.org/10.1097/sla.0000000000001184 ; Monden et al. in J Hepatobil Pancreat Sci 29(1):66-81, 2022. https://doi.org/10.1002/jhbp.898 ). This report describes a new approach, which can reduce unwanted damage to normal tissues and complications. A 53-year-old man who has suffered from hepatitis B for 10 years was admitted for the treatment of two nodular tumors located in segment VIII. The surgical procedure began with the percutaneous injection of 5 mL, 0.025 mg/mL of ICG into the S8 portal branch by using an 18G PTCD needle under the guidance of laparoscopic ultrasound (Xu et al. in Surg Endosc 34(10):4683-4691, 2020. https://doi.org/10.1007/s00464-020-07691-5 ; Wang et al. in Ann Surg 274(1):97-106, 2021. https://doi.org/10.1097/sla.0000000000004718 ; Aoki et al. in J Am Coll Surg 230(3):e7-e12, 2020. https://doi.org/10.1016/j.jamcollsurg.2019.11.004 ), followed by liver transection on the cranial side of the liver, which used the ICG fluorescence images for exposing the roots of the middle and right hepatic veins and dissecting and ligating S8 portal pedicle. The excision specimen was sent for histopathological diagnosis. It took 200 min for the operation and 60 min for the total Pringle maneuver. The estimate of blood loss was 110 mL. The final histopathologic results of the two nodules were hepatocellular carcinoma (HCC). The patient was discharged on postoperative Day 6 with no complications. Laparoscopic anatomical liver resection of S8 has been demonstrated to be feasible. Under the guidance of laparoscopic ultrasonography, ICG positive staining was proven to be optimal for Anatomical segmentectomy.


Changes in the visual evoked potential to pattern reversal with lithium medication.
Previous reports in the literature have suggested that lithium medication does not affect the VEP to flash stimulation. It was predicted that this would not be true for pattern reversal stimulation. Seven patients had their pattern evoked potential measured using a 42' check to fractional pattern displacement of 1/4, 1/2, 3/4 and full square. The VEP was measured before, 1 week after and 5 weeks after the commencement of lithium medication. The results show that there is a significant increase in both the N65-P95 and P95-N125 amplitudes when the 'before lithium' sessions are compared to 'after lithium.' Seven normal subjects matched for the age and sex of the patient group were tested twice, once as a 'control' and a further 5 weeks after this. No significant differences were found in the 'control' sessions between patient and normal groups although a significant difference in both the N65-P95 and P95-N125 amplitude after the treatment of the patient group with lithium was found.


Proximity of off-premise alcohol outlets and heavy alcohol consumption: a cohort study.
Availability of alcohol has been associated with alcohol consumption in cross-sectional studies. We examined longitudinally whether change in proximity to off-premise (i.e., no consumption on the premises) beer and liquor outlets is associated with heavy alcohol consumption. Distances from 54,778 Finnish Public Sector study participants' homes to the nearest off-premise beer and liquor outlets were calculated using Global Positioning System-coordinates. Between-individual analyses were used to study the effects of distance to the nearest outlet on heavy alcohol use, and within-individual analyses to study the effects of a change in distance on change in heavy use. Mean follow-up time in 2000-2009 was 6.8 (standard deviation 2.0) years. In a between-individual analysis, decrease from ≥500 m to <500 m (vs. remained ≥500 m) in the distance to the nearest beer outlet increased the likelihood of incident heavy alcohol use in women (odds ratio 1.23, 95% CI 1.05-1.44), but not in men. In a within-individual analysis decrease from 500 m to 0m in log-transformed continuous distance to the nearest beer outlet increased the odds of heavy alcohol consumption in women by 13% (odds ratio 1.13, 95% CI 1.01-1.27). For the corresponding change in distance to liquor outlet the increase was 3% (odds ratio 1.03, 95% CI 0.97-1.09). Change in distance from home to the nearest off-premise alcohol outlet affects the risk of heavy alcohol consumption in women. This evidence supports policies that restrict physical availability of alcohol.


The whole is more than the sum of its parts: A qualitative investigation of body-dissatisfied college women's experiences of relational body image.
Research on relational body image suggests that women's body image changes across their important relationships, with women most at risk for maladaptive body image reporting the most extreme changes. To enrich our understanding of relational body image beyond that offered by prior psychologically-based quantitative research, the present study integrated critical-feminist approaches. Eighteen female-identified university students participated in a one-on-one semi-structured interview. Each participant first completed ratings of her body image across seven important relationships, which the interviewer used to create a graph depicting her relational body image. The interviewer shared the graph with the participant to prompt reflection on her subjective experiences of relational body image and asked her a series of questions. Reflexive thematic analysis, informed by a critical-realist framework, was used to identify themes. One overarching theme, "The Whole Is More than The Sum of Its Parts," demonstrated how relational body image may be understood as a unique configuration of interconnected factors within a specific relationship. Three subthemes then highlighted how interpersonal, idiographic, and systemic factors come together to influence subjective experiences of relational body image. The present results suggest that personalized treatment targets within specific relationships may be a worthwhile focus for future body image interventions.


"We were on our own": Mothers' experiences navigating the fragmented system of professional care for autism.
Autism is a developmental disorder that emerges in early childhood. Treatments for autism span a wide variety of professionals and paraprofessionals in the medical and educational realms. This article draws on data from a survey of 620 parents of autistic children, including 385 written narratives, to examine the experiences of mothers as they engage with this fragmented system of professional care for children with autism. Findings suggest that engagement with treatments sent families into a complex and confusing universe of diagnosis and treatment. The fragmentation of autism's professional jurisdiction between the medical and educational systems meant that mothers struggled to find comprehensive professional care that met the standards recommended by leading medical research organizations. Many mothers found it necessary to reduce their workforce participation in order to obtain and maintain their children's treatment regimes, a phenomenon that transcended social class. However, the consequences of reducing work had differential impacts on families. While married and high socioeconomic status mothers were more insulated from the potential negative effects of losing one partner's income, single and low SES mothers experienced greater precarity. These findings connect the structure and arrangement of professional jurisdictions to the experiences of parents, suggesting ways that the fragmentation of professional care for autism can have negative impacts for women, single mothers, and low SES families.


Pneumonia in neutropenic patients.
Radiologists have a special role in the management of neutropenic patients. The appropriate investigational technique, frequently targeted differential diagnosis, and the special needs of these patients, need to be understood. Early detection of a focus is the major goal in febrile neutropenic patients. As pneumonia is the most common focus, chest imaging is a special radiological task. The sensitivity of chest X-ray, especially in supine position, is known to be low; therefore, the very sensitive high-resolution CT (HRCT) became gold standard in neutropenic hosts and will probably be replaced by thin-section multislice CT (MSCT) in the near future. Costs of high-resolution CT are low in comparison to antibiotics. An infiltrate needs to be localised, so that a physician can utilise this information as a guidance for invasive procedures for further microbiological work-up. The radiological characterisation of infiltrates gives a first and rapid hint to differentiate between different sorts of infectious (typical bacterial, atypical bacterial, fungal) and non-infectious aetiologies. Follow-up investigations need careful interpretation according to disease and concomitant treatment. Due to an increased incidence of fungal infiltrates even with appropriate therapy, follow-up of an infiltrate must use further parameters in addition to lesion size. Temporary exclusion of infectious involvement of the lung with high accuracy remains of special interest for clinicians.


Ultrasound simulation in the distal radius using clinical high-resolution peripheral-CT images.
The overall objective of this research is to develop an ultrasonic method for noninvasive assessment of the distal radius. The specific objective of this study was to examine the propagation of ultrasound through the distal radius and determine the relationships between bone mass and architecture and ultrasound parameters. Twenty-six high-resolution peripheral-CT clinical images were obtained from a set of subjects that were part of a larger study on secondary osteoporosis. A single midsection binary slice from each image was selected and used in the two-dimensional (2D) simulation of an ultrasound wave propagating from the anterior to the posterior surfaces of each radius. Mass and architectural parameters associated with each radius, including total (trabecular and cortical) bone mass, trabecular volume fraction, trabecular number and trabecular thickness were computed. Ultrasound parameters, including net time delay (NTD), broadband ultrasound attenuation (BUA) and ultrasound velocity (UV) were also evaluated. Significant correlations were found between NTD and total bone mass (R2 = 0.92, p < 0.001), BUA and trabecular number (R2 = 0.78, p < 0.01) and UV and trabecular bone volume fraction (R2 = 0.82, p < 0.01). There was only weak, statistically insignificant correlation (R2 < 0.14, p = 0.21) found between trabecular thickness and any of the ultrasound parameters. The study shows that ultrasound measurements are correlated with bone mass and architecture at the distal radius and, thus, ultrasound may prove useful as a method for noninvasive assessment of osteoporosis and fracture risk.


Bone marrow-derived mononuclear cell transplantation improves myocardial recovery by enhancing cellular recruitment and differentiation at the infarction site.
Stem cell therapy in myocardial infarction is under intensive investigation; however, the mechanisms of recovery and the optimal transplantation technique remain controversial. The goal of this controlled and randomized study was to test the hypothesis that locally injected bone marrow-derived mononuclear cells can focus in on the damaged myocardium and improve cardiac function by means of active participation in remodeling. Myocardial infarction was introduced through occlusion of the circumflex coronary artery for 90 minutes in 14 piglets (24.0 +/- 4.9 kg) that were randomized to a cell-therapy group (n = 7) and a control group (n = 7). At reperfusion, autologous purified prelabeled or unlabeled cells (10(8) cells/2 mL) or saline were injected into the myocardium. Cardiac function was measured by using echocardiography preoperatively and postoperatively and at 3 weeks, when hearts were collected for histopathologic examination. The ejection fraction recovered in the cell-therapy group (P = .02) but failed to recover in the control group, and at 3 weeks, it remained at the lower level compared with that in the cell-therapy group (P = .067). The number of living cells in the necrotic area was significantly greater in the cell-therapy group (P < .001). Labeled cells were detected in the infarcted area, and they showed signs of myocyte differentiation. Furthermore, the proportional area of muscle actin-positive cells at the granulation area was higher in the cell-therapy group (P = .035). Autologous bone marrow-derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy-enhanced recovery.


Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons.
Neurons in culture can have fundamentally distinct morphologies which permit their cytological identification and the recognition of their neurites as axons or dendrites. Microtubules may have a role in determining morphology by the selective stabilization of spatially distinct microtubule subsets. The plasticity of a neurite correlates inversely with the stability of its component microtubules: microtubules in growth cones are very dynamic, and in initial neurites there is continuous incorporation of labelled subunits, whereas in mature neurites, microtubules are highly stabilized. The binding of microtubule-associated proteins to the microtubules very probably contributes to this stability. Cerebellar neurons in dissociated culture initially extend exploratory neurites and, after a relatively constant interval, become polarized. Polarity becomes evident when a single neurite exceeds the others in length. These stable neurites cease to undergo the retractions and extensions characteristic of initial neurites and assume many features of axons and dendrites. We have now studied the role of the neuronal microtubule-associate protein tau in neurite polarization by selectively inhibiting tau expression by the addition of antisense oligonucleotides to the culture media. Although the extension of initial exploratory neurites occurred normally, neurite asymmetry was inhibited by the failure to elaborate an axon.


Toxic aspergilli from pistachio nuts.
Pistachio nut samples taken during various stages of development from orchards in Iran, showed that contamination with fungi occurred mainly during the later stages of nut development. Members of the genera Aspergillus and Penicillium occurred most frequently. Of the Aspergilli, the species A. niger, A. flavus and A. fischeri var. spinosus occurred most frequently, followed by A. terreus, A. tamarii and A. nidulans. Twenty-two isolates comprising 13 species were tested for toxicity to ducklings. Isolates of known toxic fungi included A. flavus, A. niger, A. parasiticus, A. ochraceus, A. versicolor, A. nidulans and A. terreus. The toxicity of A. fischeri var. spinosus is reported. Chemical analysis showed that all isolates of A. flavus and A. parasiticus produced aflatoxin B1, the isolates of A. versicolor and A. nidulans produced sterigmatocystin while the toxic isolate of A. ochraceus did not produce ochratoxins.


Assessment of Carotid Artery Distensibility and Elasticity After Laparoscopic Sleeve Gastrectomy: a Prospective Study.
Although it is well known that obesity increases the risk of atherosclerosis in carotid arteries, it is not clear whether this risk changes after obesity surgery. The aim of this study was to investigate whether weight reduction with a laparoscopic sleeve gastrectomy (LSG) has any effect on distensibility and elasticity which show subclinical atherosclerosis in the carotid arteries of obese individuals. This prospective study included 130 patients (body mass index (BMI) 48.21 ± 6.97 kg/m2) who underwent LSG. The patients were followed up for 1 year. Comparisons were made of the distensibiliy and elasticity values calculated preoperatively and at 1, 3, 6, and 12 months, postoperatively. There was a statistically significant increase in distensibility and elasticity values from baseline to 1, 3, 6, and 12 months postoperatively (p < 0.001 for both comparisons). The multiple linear regression analysis was used to find the variables affecting both distensibility and elasticity. According to the results, the presence of BMI decreases distensibility percentage change level by 0.38 units (β= - 0.38, 95% CI - 0.51;- 0.25, p < 0.001). The presence of fasting plasma glucose decreases elasticity percentage change level by 0.20 units. (β= - 0.20, 95% CI - 0.39; - 0.01, p = 0.037). Carotid artery distensibility and elasticity values increase after LSG, and this change could be caused by the change in metabolic parameters and heart geometry. These results may indirectly suggest that subclinical atherosclerosis in carotid arteries has decreased after obesity surgery.


Next steps in dermatology training: choosing to enter higher speciality training and the transition from trainee to consultant dermatologist.
Junior doctors are required to make career decisions at an early stage in their postgraduate training. Trainees also feel inadequately prepared for the transition to consultant roles. To explore the key factors influencing the choice of dermatology as a postgraduate medical career and to identify the training needs required for transition from trainee to consultant. An online questionnaire was designed to identify (i) why trainees chose a postgraduate medical career in dermatology, and (ii) the training required for transition from trainee to consultant. In total, 46 responses were received from trainees in their first to final years (ST3-6), of whom 89% had undertaken an undergraduate dermatology placement, with a median duration of 2 weeks. Dermatology was considered as a career during medical school by 61% of trainees, and 41% confirmed their decision to pursue a career in dermatology during foundation training. The most influential factors involved in speciality selection were first, enjoyment of the work, second, postgraduate experience and equal third, the variety of the speciality and the regularity of working hours (P < 0.05). Mentoring was pivotal to career decision-making. Significant numbers of trainees expressed a need for training in medical leadership, such as running an outpatient clinic and supervising clinical multidisciplinary teams. Although larger numbers of trainees had training in management of dermatology services, such as service improvement (52%) and local governance/National Health Service structures (43%), significant numbers of trainees had no training in writing job plans (89%) or business plans (85%). Training was significantly deficient for personal management and self-awareness. Our study highlights important considerations in career decision-making for trainees. Training in medical leadership, management and self-awareness could be enhanced to ensure that trainees feel adequately equipped for consultant roles.


Investigating the consistency of ERPs across threatening situations among children and adolescents.
Threat sensitivity is thought to be a precursor for anxiety. Yet it remains unknown whether individuals have consistently high neural activation to different threatening situations. The current study (N = 161, Mage = 11.26, SD = 1.79) used three ERPs from different threat-related events: 1) the P3 to receiving negative feedback; 2) the ERN to making mistakes; 3) the N170 to viewing angry faces. Participants also completed self-report measures of threat sensitivity, impulsivity, and demographics. In a follow-up analysis, we also investigated whether the results replicate when using the difference score for each ERP. Youth with higher self-reported sensitivity to threats and lower self-reported impulsivity had consistently higher neural activation to threatening situations. Males also had consistently higher neural activation to threats compared with females. When using the difference score, we found that youth with higher self-reported threat sensitivity had consistently higher neural activation to threats than nonthreats. Although it is common for youth to have high neural activation during at least one threatening situation (e.g., making mistakes), only ~12% of youth have consistently high neural activation across a variety of different threats. Thus, detecting youth who are sensitive to a variety of different threats may be an important avenue to investigate to identify youth most at risk for the development of anxiety.


Aberrancies in signal transduction and cell cycle related events in Alzheimer's disease.
Neurodegeneration in Alzheimer's disease (AD) is associated with the appearance of dystrophic neuronal growth profiles that most likely reflects an aberrant attempt of neuronal repair. This process of neuronal reorganisation, which eventually goes awry and becomes a disease itself, might be initiated physiologically as a response to neuronal injuries. Minor neuronal damage due to a variety of life events or genetic pertubations that are usually compensated in the normal adult brain by adaptation and repair might thus be amplified and accumulated, thereby resulting in a progressive neurodegeneration. The present paper summarizes recent evidence supporting the hypothesis that a primary impairment of intracellular signal transduction that is mediated by a hierarchy of phosphorylation signals and associated with a aborted attempt of neurons to re-enter the cell-cycle is a key element in the pathomechanism of AD. These changes might result in malfunction of neuronal adaptation and repair and eventually lead to neuronal death. During the process of aging as well as in chronic neurodegenerative disorders such as Alzheimer's disease (AD), the continuous but rather slow action of pathogenetic factors might give room for the activation of compensatory mechanisms, serving to regain a neuronal population much of its synaptic connectivity in the presence of cell loss. An upregulation in the capacity to synthesize and store neurotransmitters (Lapchak et al., 1991), an increased expression of trophic factors (Hellweg et al., 1990; Arendt et al., 1995a,b), as well as regenerative sprouting (Fritschy and Grzanna, 1992), synaptic enlargement (Scheff et al., 1990; Lippa et al., 1992), and neosynaptogenesis (Ramirez and Ulfhake, 1992) have been described among other processes.


The role of eosinophils in asthma.
During recent years it has become apparent that the eosinophil may represent a powerful effector cell in the pathogenesis of asthma, particularly in the late asthmatic response. It can be stimulated by a number of stimuli among which PAF appears to be one of the most effective. The eosinophil is a source for a variety of proinflammatory and toxic products with profound effect in the lungs and airways. These eosinophil products mimic some of the features of asthma and the strong association of the eosinophil with asthma has led to the suggestion that asthma would be better classified as "chronic desquamating eosinophilic bronchitis." Although the evidence known to date is persuasive many questions still remain unanswered and await further investigation. Future therapeutic approaches in asthma may aim at interrupting the mechanisms leading to eosinophil bronchial accumulation and activation.


Validation of a lip fullness scale for assessment of lip augmentation.
Given the growing use of dermal fillers for cosmetic lip augmentation, a validated instrument with which to measure lip fullness is desirable in the clinic and as an efficacy endpoint in clinical studies. The authors developed and conducted a validation study of a Medicis-developed lip fullness scale. The Medicis Lip Fullness Scale consists of separate five-point scales for the upper and lower lips, with three photographs exemplifying each grade. Five board-certified dermatologists or plastic surgeons assessed 85 test photographs for each lip on two separate occasions for the first round of validation (photograph versus photograph). Three of the evaluators also graded lip fullness in 39 live subjects, followed 2 weeks later by scoring of the same subjects' photographs for the second round of validation (live versus photographic). Within-observer agreement between the two sequential photographic evaluations was almost perfect (weighted κ = 0.81). Between-observer weighted κ values ranged from 0.60 to 0.83 for the upper lip and 0.61 to 0.82 for the lower lip. Exact agreement between the live and photographic assessments of the same subjects was 60 percent and 52 percent for upper and lower lips, respectively. The Medicis Lip Fullness Scale showed high interrater and intrarater reliability in comparisons of test photographs and moderate to substantial reliability in live assessment of patients versus photographs. The Medicis Lip Fullness Scale is suitable for grading lip fullness in clinical trials. Diagnostic, III.


Asthma from childhood to adulthood--a follow-up study of 20 subjects with special reference to work capacity and pulmonary gas exchange.
Twenty men with a mean age of 24.9 years, who had moderate to severe asthma during childhood, underwent a follow-up examination of their physical fitness, working capacity, maximal oxygen uptake, and pulmonary function during and after physical work. Comparison was made with similar data obtained at the age of 10.9 years. The young men had a normal physical working capacity with a normal oxygen uptake of 3.65 +/- 0.56 L/min. The respiratory parameters and the arterial blood gases during work demonstrated values as in healthy individuals, and no differences between groups with mild and severe asthma during childhood were observed. The alveolar-arterial oxygen difference was normalized, compared to that at 10.9 years. Only a few subjects still had exercise-induced asthma with a postexercise fall of greater than 20% in FEV1 compared to childhood. The mean FEV1 values for the whole group after exercise were lowered and had not returned to the baseline level even after 20 minutes. Oxygen pressure (tension), arterial, measured during 20 minutes after work, demonstrated continuously decreasing values. This might reflect a persisting disturbance in the pulmonary ventilation perfusion relationship caused by the underlying asthma disease.


Introduction of transcatheter aortic valve replacement technology increases overall aortic valve surgical volume: Evaluating the Florida experience.
Transcatheter aortic valve replacement technology is increasingly used for aortic valve stenosis. We sought to evaluate the adoption of transcatheter aortic valve replacement technology with respect to overall surgical aortic valve replacement volume in Florida. The 2010-2019 Florida Agency for Health Care Administration data set was queried. Difference-in-difference analysis was used to evaluate the impact of transcatheter aortic valve replacement on the total aortic valve surgical volume of transcatheter aortic valve replacement versus nonperforming hospitals. Length of stay and elements of charges were compared for the raw and 1:1 propensity matched data. A total of 46,032 surgical aortic valve procedures were performed at 88 hospitals. Transcatheter aortic valve replacement performing hospitals experienced a 21% increase in total aortic valve surgical volume. Length of stay was significantly less for patients undergoing transcatheter aortic valve replacement. Propensity matched transcatheter aortic valve replacement patients had less gross total charges. Introduction of transcatheter aortic valve replacement technology significantly increased overall surgical aortic valve volume and may be associated with less gross total hospital charges.


Free fatty acids and arrhythmias following acute coronary artery occlusion in pigs.
The arrhythmogenic potential of elevated serum free fatty acids (FFA) was investigated in closed-chest pigs following acute coronary artery occlusion. Animals both with and without ventricular irritability before the FFA rise were studied. No significant increase in PVC frequency occurred and only 1 out of 17 animals developed ventricular fibrillation in the 60 min following acute FFA elevation. In this situation, FFA did not significantly influence the appearance of arrhythmias.


A multilayered approach to approximating solute polarization.
A hybrid multilayered "ONIOM"-type approach to solvation is presented in which the basic free energy of hydration is taken from the Poisson Boltzmann method and the contribution to the solute polarization is taken from a quantum mechanical implementation of the Born method. The method has been tested on the 52 neutral molecules used in the AM1-SM2 parameterization, and the polarized continuum method is taken as the standard by which the results are assessed. Regression analysis shows that the method gives a small improvement over the standard Poisson Boltzmann method or a dramatic improvement over the Born method. The system presented here represents one of the more straightforward applications of the multilayered approach to solvation, but other more sophisticated approaches are discussed.


Treatment of late-presenting malperfusion and aneurysmal degeneration in chronic type B aortic dissection with an off-the-shelf four-vessel inner-branched endograft.
Acute complicated type B aortic dissection is increasingly treated with endovascular techniques to manage contained rupture or end-organ malperfusion. Most cases of malperfusion occur during the acute phase of the dissection. We report a case of a patient treated for late presentation of lower body malperfusion 4 years after successful endovascular intervention for contained rupture of an acute type B dissection. The anatomic complexity required multiple staged procedures culminating in endovascular repair of the paravisceral aorta with an off-the-shelf four-vessel inner-branched endograft, used for the first time, to the best of our knowledge, in North America in the present case. The patient involved provided written informed consent for the report of his case details and imaging studies.


Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing.
The bioactive lysophospholipids, primarily lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), are recent additions to the list of potent mediators of tissue repair and wound healing. In this review, we highlight the diverse actions of LPA and S1P on many types of cells involved in the wound healing process, with special emphasis on their regulation of fibroblasts. The effects of LPA and S1P are principally mediated via specific cell surface receptors. Important signaling pathways downstream of these receptors and the importance of TGFbeta and S1P cross-talk for wound healing are also discussed. Moreover, specific agonists and antagonists of the lysophospholipid receptors may be useful for the treatment of wounds and abnormal wound healing.


Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes.
Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUCEGP) and rate of glucose disappearance (AUCRd) over 45 min from exercise start. A novel application of linear regression of Rd across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUCRd increased 12.45 mmol/L (CI = 10.33-14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01-15.26, P < 0.001) whereas AUCEGP increased 1.66 mmol/L (CI = 1.01-2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81-4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUCEGP increased during intense exercise by 2.14 mmol/L (CI = 0.91-3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUCRd equal to 0.06 mmol/L per % above basal rate (CI = 0.05-0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451.NEW & NOTEWORTHY Separating insulin and non-insulin glucose uptake dynamically during exercise in type 1 diabetes has not been done before. We use a multistep process, including a previously described linear regression method, over three insulin infusion sessions, to perform this separation and can graph these components before, during, and after exercise for the first time.


Phenotypic evolution in marmoset and tamarin monkeys (Cebidae, Callitrichinae) and a revised genus-level classification.
Marmosets and tamarins (Cebidae, Callitrichinae) constitute the most species-rich subfamily of New World monkeys and one of the most diverse phenotypically. Despite the profusion of molecular phylogenies of the group, the evolution of phenotypic characters under the rapidly-emerging consensual phylogeny of the subfamily has been little studied, resulting in taxonomic proposals that have limited support from other datasets. We examined the evolution of 18 phenotypic traits (5 continuous and 13 discrete), including pelage, skull, dentition, postcrania, life-history and vocalization variables in a robust molecular phylogeny of marmoset and tamarin monkeys, quantifying their phylogenetic signal and correlations among some of the traits. At the family level, our resulting topology supports owl monkeys (Aotinae) as sister group of Callitrichinae. The topology of the callitrichine tree was congruent with previous studies except for the position of the midas group of Saguinus tamarins, which placement as sister of the bicolor group did not receive significant statistical support in both Maximum Parsimony and Bayesian Inference analyses. Our results showed that the highest value of phylogenetic signal among continuous traits was displayed by the long call character and the lowest was exhibited in the home range, intermediate values were found in characters related to osteology and skull size. Among discrete traits, pelage and osteology had similar phylogenetic signal. Based on genetic, osteological, pelage and vocalization data, we present an updated genus-level taxonomy of Callitrichinae, which recognizes six genera in the subfamily: Callimico, Callithrix, Cebuella, Mico, Leontopithecus and Saguinus. To reflect their phenotypic distinctiveness and to avoid the use of the informal "species group", we subdivided Saguinus in the subgenera Leontocebus, Saguinus and Tamarinus (revalidated here).


Assessment of the quality and content of clinical practice guidelines (CPGs) for vitamin D and for immigrants using the AGREE-II instrument: a protocol for systematic review.
Worldwide, more immigrants experience vitamin D (vitD) deficiency than non-immigrants, which is attributed to ethnic variations, place or region of birth, skin pigmentation, clothing style, and resettlement-related changes in diet, physical activity, and sun exposure. Current recommendations in clinical practice guidelines (CPGs) concerning vitD are inadequate to address vitD deficiency among immigrants. CPGs may also lack guidance for physicians on vitD supplementation for immigrants. Moreover, there are concerns about the overall quality of these CPGs. This systematic review will collate and critically appraise CPGs relevant to immigrants' health and vitD. Moreover, we will evaluate whether the CPGs of vitD including recommendations for immigrants and clarify whether the CPGs of immigrants include recommendations on vitD. A systematic search of Ovid MEDLINE® ALL, EMBASE, and Turning Research Into Practice (TRIP) electronic databases, guideline repositories, and gray literature will be conducted to identify relevant CPGs. Two reviewers will independently evaluate the methodological quality of the retrieved guidelines using the Appraisal of Guidelines, Research, and Evaluation-II (AGREE-II) instrument. CPGs scoring ≥60% in at least four domains, including "rigor of development," will be considered high quality. Evaluating the quality and content of relevant CPGs may support researchers in developing national and global guidelines for immigrants. Furthermore, it may support vitD testing, nutritional counseling, and supplementation for vulnerable immigrant sub-populations. PROSPERO CRD42021240562.


Clinical governance--bridging management and clinical approaches to quality in the UK.
Clinical governance has, for the first time, placed the quality of healthcare as a direct responsibility of the Chief Executive and therefore the board of all NHS Trusts (Hospital), community providers and primary care trusts (general practitioners). The foundation for clinical governance was set out in the Department of Health Publication 'A first class service-quality in the new NHS' [Department Of Health, A First Class Service: Quality in the New NHS, London, HMSO, 1998]. Much of this had been precipitated by the Bristol cardiac surgery case and other series of medical disasters in the UK relating to cervical screening, breast screening, psychiatric care and pathological misdiagnoses. This new responsibility of clinical governance involves guaranteeing quality through a number of processes, many of which are currently in use and should be familiar to any clinician or manager. They include clinical effectiveness and optimisation of clinical care, clinical risk management, learning from complaints, professional development, good quality clinical data systems and involvement of patients and carers. This duty is equal to the other statutory responsibilities of NHS organisations, which are of financial probity, accountability and ensuring value for public money on behalf of the taxpayer.


Role of non-Saccharomyces yeasts in Korean wines produced from Campbell Early grapes: potential use of Hanseniaspora uvarum as a starter culture.
Several yeasts were isolated from Campbell Early grapes (Vitis labrusca cultivar Campbell Early), the major grape cultivar in Korea, grown in two different regions. PCR-RFLP analysis of the ITS I-5.8S-ITS II region showed that 34 isolates out of a total of 40 were in the same group. Phylogenetic analysis revealed that the major strain belonged to one species, Hanseniaspora uvarum, although they displayed some nucleotide mismatches between them. During spontaneous alcohol fermentation at 20 °C, the two grape musts containing 24 °Brix sugar exhibited similar fermentation patterns with differences in final alcohol production and yeast viable counts. PCR analysis of the yeasts randomly isolated during the fermentation using an intron splice site primer showed changes in yeast flora between 8 and 10 days of fermentation. We found that the dominant yeasts displaying various PCR patterns using the primer remained the same throughout the early stages of fermentation, as determined by molecular typing of their ITS regions using PCR-RFLP, and these yeasts were identical to those isolated from grape berries. Among the isolates, the strain designated SS6 was selected based on its potassium metabisulfite resistance, alcohol production (distillation method), and flavor (by sniffing test) of grape juice. When Campbell Early grape must was inoculated with H. uvarum SS6 cells, no differences in fermentation pattern were observed compared with that inoculated with cells of Saccharomyces cerevisiae W-3, an industrial wine yeast strain. However, SS6 wine showed higher levels of organic acid (especially lactic acid), aldehydes, and minor alcohols (except n-propyl alcohol), as well as a higher score in sensory evaluation, compared to those of W-3 wine.


Amniotic fluid concentrations of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11, 16-cyclo-prostaglandin E2 (PGEM-LL) in preterm labor.
Although prostaglandins (PGs) are considered the key mediators of human parturition at term, there is a paucity of data regarding their participation in the mechanisms responsible for preterm labor. The purpose of this study was to establish if preterm labor is associated with changes in the amniotic fluid concentrations of prostaglandins. PGF2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 (PGEM-ll) were measured by using specific and sensitive radioimmunoassays. Amniotic fluid was retrieved by transabdominal amniocentesis from 55 women with preterm labor and intact membranes. Patients were divided into three groups according to the response to tocolysis and the presence or absence of an intra-amniotic infection. Amniotic fluid concentrations of PGFM and PGEM-ll were significantly greater in women with preterm labor and intra-amniotic infection than in women without infection. In addition, patients unresponsive to tocolysis without intra-amniotic infection also had a significantly greater concentration of PGFM and PGEM-ll in amniotic fluid than those responsive to tocolysis. Amniotic fluid concentrations of PGF2 alpha were greater in women with intra-amniotic infection than in women without intra-amniotic infection. In the absence of intra-amniotic infection, no difference in amniotic fluid PGF2 alpha concentrations could be found between women who responded to tocolytic treatment and those who did not.


Assessing the effectiveness of integrated interventions: terminology and approach.
Integrated care is a term that embraces several concepts, all of which imply that the target patients have complex or chronic illness. There is an assumption that such patients require integrated care and benefit from it. Attempts to test this hypothesis have produced evidence of only modest benefit, and much of the evidence is conflicting. Demonstration of effectiveness of integrated interventions in the clinical setting has been less convincing. Often, interventions are introduced uncritically and without adequate follow-up of their effectiveness. More rigorous research is required on definitions, theoretic constructs,outcome measures, the science of data synthesis, and translation to the clinical setting. Recent developments in theoretic constructs in these areas give promise of better answers to the question, "What works for whom in what context?". Qualitative methodology should form part of this research.


The relationship of three common definitions of the metabolic syndrome with sub-clinical carotid atherosclerosis.
Presence of the metabolic syndrome (MetS) increases a patient's risk for future cardiovascular disease. However, there is no consensus as to which of the proposed definitions should be used. Therefore, using carotid atherosclerotic burden as an index of cumulative effects of atherosclerotic risk factors, we assessed the association of the three commonly used MetS definitions with sub-clinical atherosclerosis in a primary prevention population and determined if this association was independent of the component risk factors. A multi-ethnic cohort of 796 men and women without cardiovascular disease was assessed for demographics, risk factors, properties of the carotid arteries using ultrasound and presence or absence of MetS based on each of the World Health Organization (WHO), the National Cholesterol Education Program Expert Panel (NCEP) and the International Diabetes Federation (IDF) definitions. Using any definition, 29% of the cohort had MetS. After adjusting for age, gender, ethnicity and smoking status, participants with MetS had greater intima-media thickening and total area (intima-media area and focal lesion area combined) than participants without MetS. Only participants meeting the WHO MetS criteria had a greater prevalence of focal lesions. After further adjustment for the individual risk factor components of each MetS definition separately, none of MetS definitions was associated with any of the carotid artery measures. All three MetS definitions were associated with measures of sub-clinical carotid atherosclerosis and these associations were entirely mediated through the risk factor components of MetS.


Efficacy of reversal of aortic calcification by chelating agents.
Elastin-specific medial vascular calcification, termed "Monckeberg's sclerosis," has been recognized as a major risk factor for various cardiovascular events. We hypothesize that chelating agents, such as disodium ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and sodium thiosulfate (STS) might reverse elastin calcification by directly removing calcium from calcified tissues into soluble calcium complexes. We assessed the chelating ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA) powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We show that both EDTA and DTPA could effectively remove calcium from HA and calcified tissues, while STS was not effective. The tissue architecture was not altered during chelation. In the animal model of aortic elastin-specific calcification, we further show that local periadventitial delivery of EDTA loaded in to poly(lactic-co-glycolic acid) nanoparticles regressed elastin-specific calcification in the aorta. Collectively, the data indicate that elastin-specific medial vascular calcification could be reversed by chelating agents.


DNA polymerase eta protects human cells against DNA damage induced by the tumor chemotherapeutic temozolomide.
Human DNA polymerases can bypass DNA lesions performing translesion synthesis (TLS), a mechanism of DNA damage tolerance. Tumor cells use this mechanism to survive lesions caused by specific chemotherapeutic agents, resulting in treatment relapse. Moreover, TLS polymerases are error-prone and, thus, can lead to mutagenesis, increasing the resistance potential of tumor cells. DNA polymerase eta (pol eta) - a key protein from this group - is responsible for protecting against sunlight-induced tumors. Xeroderma Pigmentosum Variant (XP-V) patients are deficient in pol eta activity, which leads to symptoms related to higher sensitivity and increased incidence of skin cancer. Temozolomide (TMZ) is a chemotherapeutic agent used in glioblastoma and melanoma treatment. TMZ damages cells' genomes, but little is known about the role of TLS in TMZ-induced DNA lesions. This work investigates the effects of TMZ treatment in human XP-V cells, which lack pol eta, and in its complemented counterpart (XP-V comp). Interestingly, TMZ reduces the viability of XP-V cells compared to TLS proficient control cells. Furthermore, XP-V cells treated with TMZ presented increased phosphorylation of H2AX, forming γH2AX, compared to control cells. However, cell cycle assays indicate that XP-V cells treated with TMZ replicate damaged DNA and pass-through S-phase, arresting in the G2/M-phase. DNA fiber assay also fails to show any specific effect of TMZ-induced DNA damage blocking DNA elongation in pol eta deficient cells. These results show that pol eta plays a role in protecting human cells from TMZ-induced DNA damage, but this can be different from its canonical TLS mechanism. The new role opens novel therapeutic possibilities of using pol eta as a target to improve the efficacy of TMZ-based therapies against cancer.


[Time in a rehabilitation unit].
In a rehabilitation unit, time is organised and activities punctuate the patient's and health professionals' day. This time is interspersed with the time of perception, time for thinking and anxiety, slow time, sequenced by the acceptance of the disability.


An extremely rare case of feeding jejunostomy proceeding to intussusception.
Feeding jejunostomy (FJ) is one of the frequently performed surgical procedures for enteral nutrition, but intussusception a very rare complication with quite challenging clinical outcome. It symbolizes a surgical emergency requiring prompt diagnosis. Feeding jejunostomy (FJ) is a minor surgical intervention, which might lead to consequences that are potentially fatal. Mechanical issues such as infection, tube dislocation or migration, electrolyte and fluid imbalances, as well as complaints of gastrointestinal tract, are the most frequent consequences. A 76-year-old female, who is a known case of carcinoma (CA) esophagus: Stage 4 with Eastern Cooperative Oncology Group (ECOG) Class 3 presented with complaints of difficulty in swallowing and vomiting. As a part of palliative treatment, FJ is done and patient was discharged on postoperative day (POD) 2. Patient again presented to emergency department after 2 months with complaints of pain abdomen, unable to pass flatus and stools for 2 days. Contrast-enhanced computed tomography was done, which revealed intussusception of jejunum with lead point as tip of feeding tube. Intussusception of jejunal loops is noted 20 centimeters distal to the site of insertion of FJ tube with tip of feeding tube as lead point. Reduction of bowel loops was achieved by gentle compression of distal part and are found to be viable. FJ tube was then removed and repositioned after which the obstruction got relieved. Intussusception is an extremely rare complication of FJ, where the clinical presentation can be likely to the various causes of small bowel obstruction. The fatal complications like intussusception in FJ can be prevented by remembering some technical considerations, such as attaching a 4-5 cm segment of the jejunum to the abdominal wall rather than a single-point fixation and maintaining a minimum distance of 15 cm between the duodenojejunal (DJ) flexure and the FJ site.


Glycogen synthase kinase 3-β: a master regulator of toll-like receptor-mediated chronic intestinal inflammation.
A disturbed regulation of Toll-like receptor (TLR) signal transduction resulting in the exclusive activation of proinflammatory signaling pathways may be critical for the perpetuation of established chronic colitis. Glycogen synthase kinase 3-β (GSK3-β) was recently identified as an important regulator of TLR signaling mediating excessive inflammatory responses. The aim of this study was to assess the role of GSK3-β activity in chronic intestinal inflammation. Chronic colitis was induced by dextran sodium sulfate (DSS) treatment. Mice were treated intraperitoneally with phosphate-buffered saline (PBS), CpG-ODN, or GSK3-β inhibitors (SB216763, LiCl). Intestinal inflammation was evaluated by histologic analysis and cytokine secretion of mesenteric lymph node cells (MLC). Nuclear extracts of MLC and lamina propria mononuclear cells (LPMC) were analyzed for nuclear factor kappaB (NF-κB) and CREB activity. Murine and human intestinal immune cells were stimulated in vitro with CpG-ODN, lipopolysaccharide (LPS), or anti-CD3 with or without LiCl. GSK3-β blockade significantly reduced chronic intestinal inflammation and even abolished the colitis-intensifying effects of CpG-ODN treatment. In vitro inhibition of GSK3-β reduced the proinflammatory phenotype of both murine and human intestinal immune cells from chronic inflamed tissue. In vivo blockade of GSK3-β resulted in a shift from NF-κB activity toward CREB activity in murine MLC and LPMC. Blockade of GSK3-β attenuates excessive proinflammatory TLR-mediated immune responses. GSK3-β inhibition therefore constitutes a promising therapeutic option for selectively reducing exaggerated intestinal immune reactions toward the luminal flora in inflammatory bowel disease.


Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study.
We studied retrospectively, 219 episodes of diabetic ketoacidemia in 119 patients aged 13 months to 30 years, to determine the trend of the concentration of sodium in serum as glucose declined during treatment of uncomplicated episodes and of episodes with complications attributable to brain swelling. Of 20 complication, 13 were minor (headache only) and 7 major (death or near death). The concentration of sodium in serum failed to rise as that of glucose declined in 82 (54%) of 164 uncomplicated episodes and in 18 (95%) of 20 complicated episodes (p less than 0.01). Hence complications were more likely to occur among patients with a failure of the concentration of sodium to rise as glucose declined. Fifty-eight episodes of diabetic ketoacidemia in 40 patients aged 1 1/2 to 20 years were then studied prospectively on a 48-hour treatment plan to provide the volume of deficit evenly, with half the deficit of sodium in the first 42 hours. Sodium concentration in serum rose in 55 (95%) of 58 episodes as that of glucose declined. No patient had a major complication. We conclude that failure of the sodium concentration measured in serum to rise as glucose concentration declines is a marker for excessive administration of free water. An expanded repair period, with repair fluid containing an average of 125 mmol/L Na+ early in therapy, will usually protect against a downward trend in the concentration of sodium in serum and therefore against a rapid decline in effective serum osmolality. This regimen may be protective against near-death episodes and brain herniation during treatment.


Prevalence and correlates of malnutrition risk among Chinese centenarians and oldest-old adults.
This study was to explore epidemiological characteristics of malnutrition and factors associated with malnutrition in centenarians and oldest-old adults, so as to provide a reference for family members and government departments to take effective measures and promote healthy aging. Median age of all 1,654 participants was 100 (85, 102) years old, and prevalence of high malnutrition risk was 65.54% in all participants. Proportion of high-malnutrition risk was higher, and proportion of normal physical function was lower, in centenarians than those in oldest-old adults (p < 0.05 for all). Univariate and multivariate Poisson regression analyses showed that normal physical function was negatively associated with malnutrition risk in all participants, centenarians, and oldest-old adults (p < 0.05 for all). In conclusion, proportion of centenarians at malnutrition risk was significantly higher than that of oldest-old adults, and the independent factor associated with malnutrition in people aged over 80 years was physical function.


ALOX5 promoter genotype and response to montelukast in moderate persistent asthma.
It was hypothesized that asthmatic patients with mutant alleles in the leukotriene pathway should not respond to leukotriene receptor antagonists and the concept of a tailored treatment is increasingly supported. Sixty-one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma were clinical and immunological assess prior and after a 6-month treatment with montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to -176) of 5-lipoxygenase gene (ALOX5). Thirty-two patients (52.5%) were homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5 repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast treatment decrease number of asthma exacerbations, improvement of FEV(1) and decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5 repeats. Conversely, the patients with 4/4 repeats genotype did not modify these data after treatment. It was confirmed that ALOX5 promoter polymorphisms have a clear influence in montelukast response in atopic moderate persistent asthma patients. The genetic study could identify those patients most likely to respond to montelukast.


MoFlow: visualizing conformational changes in molecules as molecular flow improves understanding.
Current visualizations of molecular motion use a Timeline-analogous representation that conveys "first the molecule was shaped like this, then like this...". This scheme is orthogonal to the Pathline-like human understanding of motion "this part of the molecule moved from here to here along this path". We present MoFlow, a system for visualizing molecular motion using a Pathline-analogous representation. The MoFlow system produces high-quality renderings of molecular motion as atom pathlines, as well as interactive WebGL visualizations, and 3D printable models. In a preliminary user study, MoFlow representations are shown to be superior to canonical representations for conveying molecular motion. Pathline-based representations of molecular motion are more easily understood than timeline representations. Pathline representations provide other advantages because they represent motion directly, rather than representing structure with inferred motion.


Efficacy and safety of a popular thermogenic drink after 28 days of ingestion.
We have recently demonstrated that consuming a thermogenic drink (TD) acutely increases energy expenditure and serum markers of lipolysis in healthy, college-aged individuals. The purpose of this study was to determine if consuming TD over 28 days affects its acute thermogenic and lipolytic effects as well as body composition and clinical chemistry safety markers. Sixty healthy, males (mean +/- SE; 23 +/- 1 years, 177 +/- 2 cm, 81.7 +/- 2.1 kg, 22.8 +/- 1.4% body fat; n = 30) and females (23 +/- 1 years, 166 +/- 2 cm, 62.1 +/- 1.8 kg, 28.3 +/- 1.4% body fat; n = 30) reported to the laboratory on day 0 (T1) for determination of body composition, resting energy expenditure (REE) as well as glycerol and free fatty acid (FFA) levels before and after ingesting either 336 ml of TD or a non-caloric, non-caffeinated placebo (PLA) drink. Following day 0, participants supplemented daily with 336 ml.day-1 of either TD or PLA and repeated identical testing procedures on day 28 (T2). Day 28 area under the curve (AUC) values were calculated for REE, FFA, and glycerol. Day 28 acute data and prolonged AUC comparisons between groups were analyzed using ANOVAs with repeated measures. Percent body fat (p = 0.02) and fat mass (p = 0.01) decreased in the TD group compared to the PLA group after 28 days. Day 28 FFA AUC values (p = 0.048) were greater in the TD group compared to the PLA group. There was no significant difference in day 28 REE AUC values (p = 0.30) or glycerol AUC values (p = 0.21), although a significant increase in REE values in the PLA group may have confounded these findings. There were no differences between groups concerning blood and clinical safety markers. Within-group elevations in FFA and REE values in the TD group were still evident following a 28-day supplementation period which may contribute to the observed decrements in %BF. Further, prolonged TD supplementation did not alter the assessed clinical safety markers. Future studies should examine the synergistic and independent effects of the active ingredients in addition to effects of longer ingestion periods of TD ingestion with or without exercise at promoting and sustaining changes in body composition.


Genotypic differentiation of intrahepatically transplanted hyperplastic nodule cells of analbuminemic and normal rat origin by polymerase chain reaction.
DNA fragments encompassing the region of the seven-base-pair deletion in the albumin gene, which is a characteristic abnormality of Nagase's analbuminemic rat (NAR), were amplified by polymerase chain reaction, and we could differentiate the genotypes of normal rat, homozygous NAR and heterozygous NAR electrophoretically. This genotyping method was applied to the differentiation of hyperplastic nodules on immunostained tissue sections in the intrahepatic transplantation model. When the hyperplastic nodule cells of normal rat were transplanted to the livers of homozygous NAR, the donor cells were effectively differentiated from the host cells by the genotype.


A Danish version of the life-space assessment (LSA-DK) - translation, content validity and cultural adaptation using cognitive interviewing in older mobility limited adults.
Identification and prevention of mobility limitations in older adults is important to reduce adverse health outcomes. The Life-Space Assessment (LSA) provides a single measure of mobility including environmental and social resources of the older adult. Availability of the LSA for non-English speaking countries is still sparse. Therefore, we translated the LSA into Danish and performed a content validity analysis of the translation in older adults with mobility limitations. After translation into Danish, the Danish version (LSA-DK) was content validated using cognitive interviewing in older mobility limited adults (+ 65) from an outpatient rehabilitation center (n = 12), medical wards at a university hospital (n = 11), and an assisted living facility (n = 7). The interviews were transcribed and analyzed according to the four stages of the Information Processing Model. Based on the analyses, recommendations for changes to the LSA-DK and to the manual were made and presented to the developers of the LSA. Consensus was reached on the LSA-DK. Thirty cognitive interviews were carried out. A wide range of sources of error primarily related to the comprehension, memory and decision process were identified. The frequency and type of error sources were most prevalent among assisted living facility informants and included difficulties in defining the geographical extension of neighborhood, town and outside town. The results led to adaptations to the questionnaire and manual to support implementation of the LSA-DK in clinical practice. The Life-Space Assessment was translated into Danish and content validated based on cognitive interviews. Adaptations were made to support that the Danish version can be implemented in clinical practice and used in the assessment of mobility in older Danish adults.


Academic Cyberslacking: Why Do Students Engage in Non-Academic Internet Access During Lectures?
University students, as members of the digital generation, often access the internet for non-academic purposes while attending lectures in the classroom. Internet access for non-academic purposes during lectures is known as academic cyberslacking. This study aims to test the effects of media multitasking, self-efficacy, self-regulation, social media engagement, and Attention, Relevance, Confidence, and Satisfaction (ARCS) motivation, on the engagement in academic cyberslacking by university students. The participants were 1485 university students, who had previously engaged in academic cyberslacking during lectures. The research instruments in this study were an academic cyberslacking scale, a media multitasking self-efficacy scale, a self-regulation scale, a social media engagement scale, and an ARCS motivation scale. The research model and hypotheses are tested using structural equation model (SEM) by Lisrel. Confirmatory factor analysis (CFA) is also used to analyze all the instruments. The respondents' demographic data were analyzed using SPSS. The results showed that it is only media multitasking self-efficacy and social media engagement which have any significant effects regarding academic cyberslacking. Self-regulation and ARCS motivation do not have direct association with academic cyberslacking. Students do academic cyberslacking during lectures. Media multitasking self-efficacy and social media engagement can predict students' academic cyberslacking. It is recommended that students direct their involvement in the digital environment to more constructive efforts during lectures.


Violence at the Intersections of Women's Lives in an Urban Context: Indigenous Women's Experiences of Leaving and/or Staying With an Abusive Partner.
This article is based on an ethnographic study exploring Indigenous women's experiences of leaving intimate partner violence. Analysis draws attention to the contextual features of Indigenous women's lives that differentially shaped women's experiences of "leaving and/or staying" with an abusive partner. Our findings are identified and described across four intersecting thematic areas: (a) the context of state-Indigenous relations; (b) complex trauma, stigma, and discrimination; (c) kinship and ties to communities and the land; and (d) health, healing, and resistance. These findings offer valuable insights into what constitutes appropriate, safe services, and support for the Indigenous women whose lives are shaped by multiple forms of violence.


Stereoselective total syntheses of uncommon sesquiterpenoids isolated from Jatropha neopauciflora.
The first total syntheses of two tricyclic sesquiterpenes 1 and 2, isolated from Jatropha neopauciflora, were completed from dimethyl D-tartrate in a stereoselective manner. The crucial steps in these syntheses involved not only the Rh(I)-catalyzed Pauson-Khand-type reaction of the allenene derivative leading to the exclusive formation of the bicyclo[4.3.0]nonenone framework possessing an angular methyl group but also a highly stereoselective construction of the isopropylcyclopropane ring.


The runaway greenhouse and the accumulation of CO2 in the Venus atmosphere.
Conditions on Earth would be as hostile as on Venus if the Earth were closer to the Sun by only 6-10 million miles.


Quantitative Evaluation of Intravoxel Incoherent Motion and Diffusion Kurtosis Imaging in Assessment of Pathological Grade of Clear Cell Renal Cell Carcinoma.
To evaluate the diagnostic value of intravoxel incoherent motion and diffusion kurtosis imaging parameters for clear cell renal cell carcinoma (ccRCC) grading. A total of 60 patients with pathologically proven ccRCC who underwent intravoxel incoherent motion and diffusion kurtosis imaging were retrospectively evaluated. The standard apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) maps were calculated and compared between high-grade and low-grade ccRCC using Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters. ADC, D and MD values were significantly lower for high-grade ccRCC compared to low-grade ccRCC (p < 0.05). MK values were significantly higher in high-grade ccRCC compared to low-grade ccRCC (p < 0.05). However, D* and f were not significantly difference between the two groups (p > 0.05). MD had the largest area under the curve (AUC = 0.888), followed by ADC (AUC = 0.796), D (AUC = 0.780), MK (AUC = 0.736), f (AUC = 0.582), and D*(AUC = 0.533). Diffusion-related parameters (D, ADC, MD, and MK) were able to significantly distinguish between low- and high-grade ccRCC. However, perfusion-related parameters (D* and f) were unable to separate high- and low-grade ccRCC. MD may be the most promising parameter for grading ccRCC in the clinic.


Simultaneous Resection of Pancreatic Neuroendocrine Tumors with Synchronous Liver Metastases: Safety and Oncological Efficacy.
Whether the simultaneous resection of pancreatic neuroendocrine tumors (PNET) with synchronous liver metastases (LM) is safe and oncologically efficacious remains to be debated. We retrospectively reviewed clinical data from patients who underwent the simultaneous resection of PNETs with LMs over the last 25 years. Fifty-one consecutive patients with a median age of 54 years (range 27-80 years) underwent pancreaticoduodenectomy (PD) (n = 16), distal pancreatosplenectomy (DSP) (n = 32) or total pancreatectomy (n = 3) with synchronous LM resection. There were no differences in the postoperative outcomes in term of mortality (p = 0.33) and morbidity (p = 0.76) between PD and DSP. The median overall survival (OS) was 64.78 months (95% CI: 49.7-119.8), and the overall survival rates at 1, 3, and 5 years were 97.9%, 86.2% and 61%, respectively. The OS varied according to the tumor grade (G): G1 (OS 128 months, 5-year OS 83%) vs. G2 (OS 60.5 months, 5-year OS 58%) vs. G3 (OS 49.7 months, 5-year OS 0%) (p = 0.03). Multivariate Cox analysis identified G as the only prognostic factor (HR: 5.56; 95% CI: 0.91-9.60; p = 0.01). Simultaneous PNETS with LMs can be performed safely with acceptable morbidity and mortality at tertiary centers. Well-differentiated PNETs had longer survival and might benefit the most from these extended surgeries.


Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance.
An intricate interplay between genetic and environmental factors contributes to the development of type 2 diabetes (T2D) and its complications. Therefore, it is not surprising that the epigenome also plays a crucial role in the pathogenesis of T2D. Hyperglycemia can indeed trigger epigenetic modifications, thereby regulating different gene expression patterns. Such epigenetic changes can persist after normalizing serum glucose concentrations, suggesting the presence of a 'metabolic memory' of previous hyperglycemia which may also be epigenetically regulated. Metformin, a derivative of biguanide known to reduce serum glucose concentrations in patients with T2D, appears to exert additional pleiotropic effects that are mediated by multiple epigenetic modifications. Such modifications have been reported in various organs, tissues, and cellular compartments and appear to account for the effects of metformin on glycemic control as well as local and systemic inflammation, oxidant stress, and fibrosis. This review discusses the emerging evidence regarding the reported metformin-mediated epigenetic modifications, particularly on short and long non-coding RNAs, DNA methylation, and histone proteins post-translational modifications, their biological and clinical significance, potential therapeutic applications, and future research directions.


Secondary pollen carryover by ants in a natural population of Scleranthus perennis (Caryophyllaceae).
Secondary pollen carryover is defined as the process whereby a pollinator receives previously deposited pollen grains when visiting a flower and transfers them into a new (secondary) carryover sequence. The secondary pollen carryover in a system of ants, Formica rufibarbis, visiting Scleranthus perennis (Caryophyllaceae) was studied using fluorescent dyes as pollen analogues. The mean secondary carryover was found to be 1.2 flowers compared with 4.5 flowers for the primary carryover. The number of dye grains deposited per flower visited is lower and the frequency of zero deposition is higher in the secondary carryover sequence than in the primary.


Light microscopic autoradiographic localization of [3H] substance P binding sites in rat thoracic spinal cord.
We have used light microscopic autoradiography to look for the distribution of [3H] substance P receptors in the thoracic spinal cord of the rat. High densities of autoradiographic grains were localized to the intermedialateral cell column, the central canal and the substantia gelatinosa of the dorsal horn.


Highly selective determination of methylmercury with methylmercury-imprinted polymers.
Methylmercury-imprinted and non-imprinted polymers were prepared by formation monomer complex of methylmercury with (4-ethenylphenyl)-4-formate-6-phenyl-2,2'-bipyridine and thermally polymerizing with divinylbenzene (crosslinker) in the presence of 2,2'-azobisisobutyronitrile as initiator and subsequently leached with the acidic thiourea solution (1.0 mol L(-1) of thiourea and 4.0 mol L(-1) of HCl). In the same way, non-imprinted copolymers were prepared without methylmercury chloride added. The separation and preconcentration characteristics of the polymers for methylmercury were investigated by batch and column procedures. The results demonstrated that the methylmercury-imprinted polymers had higher adsorption capacity (170 micromol g(-1) of dry microbeads) and good selectivity for methylmercury compared to non-imprinted polymers. The distribution ratio (D) values of the methylmercury-imprinted polymers increased for methylmercury with respect to both D values of Hg(II), Cu(II), Zn(II), Cd(II) and non-imprinted polymers. The relatively selective factor (alpha(r)) values of CH3Hg+/Hg(II), CH3Hg+/Cu(II), CH3Hg+/Zn(II), and CH3Hg+/Cd(II) are 24.0, 46.7, 50.7, and 40.2, which are greater than 1. The methylmercury-imprinted polymers can be used at least twenty times with recoveries no less than 95%. Based on the packed columns with methylmercury-imprinted polymers, a highly selective solid-phase extraction (SPE) and preconcentration method for methylmercury was developed. The metal ion imprinted polymer solid-phase extraction (MIIP-SPE) preconcentration procedure showed a linear calibration curve within concentration range from 0.093 to 22 microg L(-1). The detection limit and quantification limit were 0.041 and 0.093 microg L(-1) (3sigma) for cold vapor atomic absorption spectrometry (CVAAS). The relative standard deviation of the 10 replicate determinations was 3.5% for the determination of methylmercury in human hair sample. Determination of methylmercury in certified human hair sample (IAEA-086) and soil certified reference material (CRM 580) demonstrated that the interfering substances in matrix had been almost removed during preconcentration. The methylmercury-imprinted polymers were good enough for methylmercury determination in matrixes containing components with similar chemical property such as Hg(II), Cu(II), Zn(II), and Cd(II).


A levodopa dry powder inhaler for the treatment of Parkinson's disease patients in off periods.
Adequate treatment of Parkinson's patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronization, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterized in vitro over a range of pressure drops (2-6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronized levodopa formulation with 2% L-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson's patients in an off period.


Management of lower vaginal agenesis in a patient with unicornuate uterus.
Absence of the lower vagina occurs from abnormal development of the sinovaginal bulbs and vaginal plate. We present a case of an adolescent girl, with a history of VACTERL and VATER status post flap vaginoplasty at 8 m of age and correction of vaginal-urethral fistula, with primary amenorrhea and cyclic pelvic pain. MRI showed a right hematocolpos. On exam the obstructed vagina was deviated to the right. Given prior urologic and rectal surgery, and laterality of unicornuate system, intra-operative ultrasonography (US) was performed. A needle was used to enter the inferior aspect of the obstructed vagina. A pull-through vaginoplasty was performed. Vaginal pull-through is the standard treatment for lower vaginal agenesis. In a unicornuate system, the use of intra-operative US is helpful to determine the appropriate angle of dissection.


Higher succinate than acetate levels differentiate cerebral degenerating cysticerci from anaerobic abscesses on in-vivo proton MR spectroscopy.
We present three patients with large intraparenchymal isolated degenerating cysticerci in whom the diagnosis was primarily based on in-vivo proton MR spectroscopy, and subsequently confirmed histologically. We suggest that the presence of succinate alone or more succinate acetate indicates the presence of degenerating cysticerci and differentiates them from anaerobic brain abscesses, which show acetate alone or in higher concentration than succinate, even when the clinical and imaging features are similar.


Diagnostic delay in rare diseases: data from the Spanish rare diseases patient registry.
According to the International Rare Diseases Research Consortium (IRDiRC), a known rare disease (RD) should be diagnosable within a year. This study sought: firstly, to ascertain how long it takes to obtain the diagnosis of a RD in Spain, along with its associated time trend; and secondly, to identify and measure diagnostic delay (defined by the IRDiRC as any period exceeding a year) by reference to the characteristics of RDs and the persons affected by them. Using data sourced from the Spanish Rare Diseases Patient Registry, we performed a descriptive analysis of the time elapsed between symptom onset and diagnosis of each RD, by sex, age and date of symptom onset, and type of RD. We analysed the time trend across the period 1960-2021 and possible change points, using a Joinpoint regression model and assuming a Poisson distribution. The multivariate analysis was completed with backward stepwise logistic regression. Detailed information was obtained on 3304 persons with RDs: 56.4% had experienced delay in diagnosis of their RDs, with the mean time taken being 6.18 years (median = 2; IQR 0.2-7.5). Both the percentage of patients with diagnostic delay and the average time to diagnosis underwent a significant reduction across the study period (p < 0.001). There was a higher percentage of diagnostic delays: in women (OR 1.25; 95% CI 1.07-1.45); in cases with symptom onset at age 30-44 years (OR 1.48; 95% CI 1.19-1.84): and when analysed by type of RD, in mental and behavioural disorders (OR 4.21; 95% CI 2.26-7.85), followed by RDs of the nervous system (OR 1.39; 95% CI 1.02-1.88). This is the first study to quantify time to diagnosis of RDs in Spain, based on data from a national registry open to any RD. Since over half of all persons affected by RDs experience delay in diagnosis, new studies are needed to ascertain the factors associated with this delay and the implications this has on the lives of patients and their families.


Adolescence: Contemporary issues in the clinic and beyond.
This article reports on a Continuing Medical Education Programme (CME), organized by the Department of Child and Adolescent Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, in March 2019. The theme, Adolescence: contemporary issues in the clinic and beyond, aimed to cover 'lesser understood and challenging' areas in adolescent mental health. The CME was attended by over 200 professionals from various fields - clinicians, post-graduate students in psychiatry, psychology and psychiatric social work, school counsellors, and members of non-governmental organisations working in the areas of childcare and law. The article covers key messages from the 8 sessions in this CME.


Inflammation, an inducer of metallothionein, inhibits carbon-tetrachloride-induced hepatotoxicity in rats.
Inflammation, induced by turpentine (0.1 ml i.m.), protected against carbon tetrachloride (CCl4)-induced hepatotoxicity based on serum activities of sorbitol dehydrogenase. Inflammation was confirmed by elevated serum ceruloplasmin activities, and was associated with high hepatic levels of metallothionein, a zinc protein proposed to protect against CCl4-induced injury. Inflammation suppressed cytochrome P-450 activities, but this was not associated with protection against CCl4-promoted liver microsomal injury as assessed by glucose-6-phosphatase activity loss. Thus, protection against plasma membrane injury did not result primarily from depressed microsomal activation of CCl4. Each effect of inflammation reported here resembled effects of zinc injections. This similarity strengthens the hypothesis that metallothionein protects against CCl4-induced hepatic plasma membrane injury.


Development of isotope dilution-liquid chromatography tandem mass spectrometry for the accurate determination of fluoroquinolones in animal meat products: optimization of chromatographic separation for eliminating matrix effects on isotope ratio measurements.
Isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-MS/MS) has been established as a candidate reference method for the accurate determination of three representative fluoroquinolone antibiotics (enrofloxacin, ciprofloxacin, and norfloxacin) in meat products. Enrofloxacin-d₅, ciprofloxacin-¹³C₃¹⁵N, and norfloxacin-d₅ were used as internal standards. After extraction and SPE clean-up, samples were analyzed by using LC-MS/MS in positive ion mode. We observed that the deuterium-labeled internal standards have slightly different LC retention time from their native analogues, which reduces the benefits of using isotope dilution techniques as ion suppression/enhancement effects caused by co-eluting matrix interferences are not completely compensated. In this study, LC conditions were optimized to minimize matrix effects causing different ionization efficiency between the target analytes and their isotope analogues by separating them from significant matrix interferences. The analytical method was validated by measuring samples (chicken breast, bovine muscle, and porcine muscle) gravimetrically fortified in various levels with the target analytes. The method provided accurate analytical results of the target analytes in the range of 5-50 μg/kg with the relative expanded uncertainty of 1-5%.


Radiation induced MMP expression from rectal cancer is short lived but contributes to in vitro invasion.
Matrix metalloproteinase (MMP) activity is increased after radiation. The aims of this study were to assess the time course of this increase and its effects on malignant cell invasion. Colorectal cancer (HCT 116, LoVo, C 170 HM 2, CaCO-2), fibroblast (46-BR.IGI, CCD-18 Co) and fibrosarcoma (HT1080) cell lines were irradiated at 4 gray (4 Gy) and matrix metalloproteinase gene and protein expression examined over a 96 h period by real time polymerase chain reaction and gelatin zymography. Invasion was assessed on Matrigel. Human rectal tumour MMP expression was compared before and after long course radiotherapy. Radiation increased MMP gene expression of tumour cell lines, and resulted in increased MMP protein activity in the HT1080 line. HT1080 and HCT 116 in monoculture and LoVo in co-culture were more invasive after radiation at 48 h in vitro, but long course radiotherapy did not result in a consistent increase in MMP expression from human rectal tumour biopsies. Radiation results in increased MMP expression for a limited time period. This results in an early increase in cell line invasion. Further clinical research is required to clarify if MMP inhibition given perioperatively following radiotherapy decreases local recurrence rates.


Breathable Nanomesh Humidity Sensor for Real-Time Skin Humidity Monitoring.
The importance of monitoring the condition of skin is increasing as its relevance to health is becoming more well understood. Inappropriate humidity levels can cause atopic dermatitis or hair loss. However, conventional film substrates used in electronic skin monitoring devices cause accumulation of sweat or gas between the device and biological tissue, leading to negative effects in long-term humidity measurements. Thus, real-time measurements of skin humidity over long periods are difficult using conventional film devices. Here, a breathable nanomesh humidity sensor that can monitor skin humidity for a long time is developed by using biocompatible materials such as gold, poly(vinyl alcohol), and Parylene C. The sensor presents excellent gas and sweat permeability and precisely detects the humidity level of an object for a long time. This study demonstrates the successful real-time detection of the humidity level from human skin and also detects the relative humidity of a plant surface over a prolonged period. This sensor is expected to have wide applicability for cultivating delicate plants as well as to reveal correlations between skin humidity and disease for biomedical applications.


Catheter tip tracking for MR-guided interventions using discrete Kalman filter and mean shift localization.
This paper presents and evaluates stochastic computer algorithms used to automatically detect and track marked catheter tip during MR-guided catheterization. The algorithms developed employ extraction and matching of regional features of the catheter tip to perform the localization. To perform the tracking, a probability map that indicates the possible locations of the catheter tip in the MR images is first generated. This map is generated from the similarity to a given marker template. The method to assess the similarity between the marker template image and the different positions on each MR frame is based on speeded-up robust features extracted from the gradient image. The probability map is then used in two different stochastic localization frameworks mean shift (MS) localization and Kalman filter (KF) to track the position of the catheter using pairs of orthogonal projection of 2D MR images. The algorithm developed was tested on catheter tip marked with LC resonant circuit (of size 2 mm x 2 cm) tuned to the Larmor frequency of the MRI scanner and for different image resolutions (1, 3, 5 and 7 mm squared pixel). The tracking performance was very robust for the two algorithms MS and KF with image resolution as low as 3 mm where the localization error was about 1 mm for KF and 0.9 mm for MS. For the 5-mm resolution images, the error was 2.2 mm for both KF and MS, and for the 7-mm resolution images, the error was 3.6 and 3.7 mm for KF and MS, respectively. Both KF and MS gave comparable results when it comes to accuracy for the different image resolutions. The results showed that the two tracking algorithms tracked the catheter tip with high robustness for image resolution of 3 mm and with acceptable reliability for image resolution as poor as 5 mm with the resonant marker configuration used.


The prevention of alloxan-induced diabetes in mice by dimethyl sulfoxide.
Dimethyl sulfoxide (DMSO, 7.3 g/kg) administered to mice prior to alloxan completely protected against the diabetogenic actions of 50 mg/kg alloxan. The same dose of DMSO provided a partial protection against 75 mg/kg alloxan. This protection against alloxan-induced diabetes is consistent with the scavenging of the hydroxyl radical by DMSO.


Application of the Champion Health Belief Model to determine beliefs and behaviors of Turkish women academicians regarding breast cancer screening: A cross sectional descriptive study.
Breast cancer is an important cancer type and the most common malignancy among women in both developed and developing countries and the second leading cause of cancer death in women worldwide. This study aimed to examine the projected risk of breast cancer in Turkish women academician, determine the levels of their breast cancer screening behaviors and uncover the relationship between their health beliefs and screening behaviors. This cross-sectional descriptive study was conducted from March to July 2018 in the province of Aydın, Turkey with a total of 200 female academicians. The data were collected using questionnaires filled out by the participants and the Turkish version of the Champion Health Belief Model Scale. Data were analyzed using t test, ANOVA, Chi-square and logistic regression performed with Statistical Package for Social Sciences version 20. The mean age of the female academics was 36.1 ± 0.53 years. The female performing breast self-examination had higher perceived sensitivity (OR = 2.88, 95% Cl 1.32, 2.66) benefits to breast self-examination (OR = 0.90, 95% Cl 0.82, 0.99), self-efficacy (OR = 0.87, 95% Cl 0.81, 0.93) health motivation (OR = 1.74, 95% Cl 0.50, 0.90), benefit to mammography (OR = 0.97, 95% Cl 0.88, 1.08), lower barrier to mammography (OR = 1.05, 95% Cl 1.0, 1.09) than women who did not. Female academics with clinical breast examination had higher self-efficacy (OR = 0.91, 95% Cl 0.86, 0.97) and lower barrier to mammography (OR = 1.06, 95% Cl 1.02, 1.10) than women who did not. The female with take mammography had higher sensitivity (OR = 0.84, 95% Cl 0.72, 0.98), lower barrier to breast self-examination (OR = 1.08, 95% Cl 1.02, 1.15) and lower barrier to mammography (OR = 1.09, 95% Cl 1.04, 1.14) than female who did not. Female academicians in Turkey exhibit positive attitudes towards breast self-examination, clinical breast examination and mammography as they have higher perceived sensitivity against breast cancer, self-efficacy and fewer barriers. Long-term community-based programs should be extended to different groups of women from a variety of socio-demographic environments.


Photocatalytic Reduction of CO2 over Heterostructure Semiconductors into Value-Added Chemicals.
Photoreduction of CO2 , which utilizes solar energy to convert CO2 into hydrocarbons, can be an effective means to overcome the increasing energy crisis and mitigate the rising emissions of greenhouse gas. This article covers recent advances in the CO2 photoreduction over heterostructure-based photocatalysts. The fundamentals of CO2 photoreduction and classification of the heterostructured photocatalysts are discussed first, followed by the latest work on the CO2 photoreduction over heterostructured photocatalysts in terms of the classification of the coupling semiconductors. Finally, a brief summary and a perspective on the challenges in this area are presented.


[Antagonistic actions of testosterone and the anti-mullerian hormone on the mullerian duct of the chick embryo in culture in vitro].
When cultured in combination with testes of the same stage, müllerian ducts from the 7-7 1/2-day-old chick embryo underwent regression, which was nearly complete in the male and less pronounced in the female after a 4-5-day culture period. When a crystal of testosterone was added in the system, the müllerian ducts were maintained in the male, whereas they were even stimulated in the female. Testosterone therefore antagonizes the suppressive action of the anti-müllerian hormone. The exact nature of the interaction of the two hormones at the cellular and molecular level should be the object of further studies.


A systematic method for estimating individual responses to treatment with antipsychotics in CATIE.
In addition to comparing drug treatment groups, the wealth of genetic and clinical data collected in the Clinical Antipsychotic Trials of Intervention Effectiveness study offers tremendous opportunities to study individual differences in response to treatment with antipsychotics. A major challenge, however, is how to estimate the individual responses to treatments. For this purpose, we propose a systematic method that condenses all information collected during the trials in an optimal, empirical fashion. Our method comprises three steps. First, we test how to best model treatment effects over time. Next, we screen many covariates to select those that will further improve the precision of the individual treatment effect estimates which, for example, improves power to detect predictors of individual treatment response. Third, Best Linear Unbiased Predictors (BLUPs) of the random effects are used to estimate for each individual a treatment effect based on the model empirically indicated to best fit the data. We illustrate our method for the Positive and Negative Syndrome Scale (PANSS). A model assuming it takes on average about 30 days for a treatment to exert an effect that will then remain about the same for the rest of the trial showed the best fit to the data. Of all screened covariates, only two improved the precision of the individual treatment effect estimates. Finally, correlations between drug effects and PANSS scales suggested that in CATIE it cannot be recommended to simply combine treatment effects across drugs (e.g. to study common drug mechanisms), but it is sensible to study how a given drug affects multiple symptom dimensions. We demonstrate that treatment effects can be estimated in a way that condenses all information collected in an optimal, empirical fashion. We expect the proposed method to be valuable for other clinical outcomes in CATIE and potentially other clinical trials.


Academic detailing as a method to improve general practitioners' drug prescribing in type 2 diabetes: evaluation of changes in prescribing.
To investigate the effect of an academic detailing intervention on the utilisation of type 2 diabetes medication among general practitioners. We developed an academic detailing campaign based on the revised national treatment guideline for diabetes and the best available evidence. General practitioners were offered a 20-minute one-to-one visit by a trained academic detailer. A total of 371 general practitioners received a visit and represented the intervention group. The control group consisted of 1282 general practitioners not receiving a visit. Changes in prescribing from 12 months before to 12 months after the intervention. The primary endpoint was a change in metformin. Secondary endpoints were changes in other groups of Type 2 diabetes medication and of these drugs in total. Prescribing of metformin increased by 7.4% in the intervention group and 5.2% in the control group (p = .043). Sodium-glucose cotransporter-2 inhibitors increased by 27.6% in the intervention group and 33.8% in the control group (p = .019). For sulfonylureas there was a decrease of 3.6% in the intervention group vs. 8.9% in the control group (p = .026). The total amount of prescribed medications for type 2 diabetes increased by 9.1% in the intervention group and 7.3% in the control group (p = .08). Academic detailing initiated a small but statistically significant increase in the prescription of metformin. For a complex subject like type 2 diabetes, we recommend reserving more time in the visit than the 20 min our campaign aimed for.